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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2003-5-27
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pubmed:abstractText |
Malignant mesothelioma (MM) is a lethal tumor linked with a prior exposure to asbestos in which limited progress has been made so far using conventional therapies. MM is an example of a "nonimmunogenic" tumor characterized by a fibrous stroma and an absence of infiltrating T lymphocytes. High levels of transforming growth factor-beta (TGF-beta) produced by mesothelioma cells have been related to the immune tolerance towards the tumor. In order to evaluate the effect of local delivery of cytokines such as interferon gamma (IFN-gamma) by gene transfer, we characterized and used a murine model, AK7, which appeared very similar to human mesothelioma. AK7 cells expressed low levels of major histocompatibility class I and class II antigens and secreted high levels of latent TGF-beta. The TGF-beta pathway in AK7 cells is operative but inefficient because endogenous TGF-beta is predominantly inactive. Treatment of pre-established AK7 tumors by direct intratumoral injection of an adenovirus vector expressing murine IFN-gamma, Ad.mIFN-gamma, led to significant tumor regression. Peripheral tumor infiltration by CD4+ and CD8+ T lymphocytes in the treated tumors appeared to be because of the induction of an immune response. Tumor relapse was observed, which could be due to local TGF-beta secretion by remaining tumor cells.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CASP3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Casp3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/RNA,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0929-1903
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pubmed:author |
pubmed-author:AbinaMohamed AmineMA,
pubmed-author:Cordier KellermanLaurenceL,
pubmed-author:DescampsVincentV,
pubmed-author:FernandezNadineN,
pubmed-author:HaddadaHédiH,
pubmed-author:KaneAgnesA,
pubmed-author:Le RoyPierreP,
pubmed-author:LegrandAgnesA,
pubmed-author:MaubecEveE,
pubmed-author:MoudniLL,
pubmed-author:SabourinJean-ChristopheJC,
pubmed-author:ValeyrieLaurenceL
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pubmed:issnType |
Print
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pubmed:volume |
10
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
481-90
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:12768194-Adenoviridae,
pubmed-meshheading:12768194-Animals,
pubmed-meshheading:12768194-Apoptosis,
pubmed-meshheading:12768194-Blotting, Western,
pubmed-meshheading:12768194-Caspase 3,
pubmed-meshheading:12768194-Caspases,
pubmed-meshheading:12768194-Cell Line, Tumor,
pubmed-meshheading:12768194-Cell Separation,
pubmed-meshheading:12768194-Cytokines,
pubmed-meshheading:12768194-DNA, Complementary,
pubmed-meshheading:12768194-Down-Regulation,
pubmed-meshheading:12768194-Female,
pubmed-meshheading:12768194-Flow Cytometry,
pubmed-meshheading:12768194-Gene Therapy,
pubmed-meshheading:12768194-Gene Transfer Techniques,
pubmed-meshheading:12768194-Immunohistochemistry,
pubmed-meshheading:12768194-Interferon-gamma,
pubmed-meshheading:12768194-Mesothelioma,
pubmed-meshheading:12768194-Mice,
pubmed-meshheading:12768194-Mice, Inbred C57BL,
pubmed-meshheading:12768194-Neoplasm Transplantation,
pubmed-meshheading:12768194-Phosphorylation,
pubmed-meshheading:12768194-Polymerase Chain Reaction,
pubmed-meshheading:12768194-RNA,
pubmed-meshheading:12768194-T-Lymphocytes,
pubmed-meshheading:12768194-Time Factors,
pubmed-meshheading:12768194-Transforming Growth Factor beta,
pubmed-meshheading:12768194-Up-Regulation
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pubmed:year |
2003
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pubmed:articleTitle |
Regression of AK7 malignant mesothelioma established in immunocompetent mice following intratumoral gene transfer of interferon gamma.
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pubmed:affiliation |
Institut Gustave Roussy, 94805 Villejuif Cedex, France.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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