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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
15
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pubmed:dateCreated |
1998-8-27
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pubmed:abstractText |
Strategies to sensitize human tumors that are resistant to apoptosis have been clinically unsuccessful. We demonstrate that a structurally modified chimeric Pseudomonas exotoxin, PEdelta53L/TGF-alpha/KDEL, with binding specificity for the epidermal growth factor receptor, markedly enhances sensitivity of human xenografts to radiation killing. Exposure to PEdelta53L/TGF-alpha/KDEL decreases the apoptotic threshold through protein synthesis inhibition and simultaneous production of ceramide in tumor cells that lack functional p53 protein. In contrast, no increase in local or systemic toxicity was observed with the chimeric toxin and radiation. We conclude that biochemical targeting of the chimeric toxin and physical targeting of ionizing radiation may increase the therapeutic ratio in the treatment of human cancers with alterations of p53 expression. This strategy offers a high therapeutic potential for Pseudomonas exotoxin A chimeric proteins and irradiation.
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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/ADP Ribose Transferases,
http://linkedlifedata.com/resource/pubmed/chemical/Bacterial Toxins,
http://linkedlifedata.com/resource/pubmed/chemical/Ceramides,
http://linkedlifedata.com/resource/pubmed/chemical/Exotoxins,
http://linkedlifedata.com/resource/pubmed/chemical/Oligopeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Sorting Signals,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p53,
http://linkedlifedata.com/resource/pubmed/chemical/Virulence Factors,
http://linkedlifedata.com/resource/pubmed/chemical/lysyl-aspartyl-glutamyl-leucine,
http://linkedlifedata.com/resource/pubmed/chemical/toxA protein, Pseudomonas aeruginosa
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0008-5472
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
58
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3215-20
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:9699644-ADP Ribose Transferases,
pubmed-meshheading:9699644-Animals,
pubmed-meshheading:9699644-Apoptosis,
pubmed-meshheading:9699644-Bacterial Toxins,
pubmed-meshheading:9699644-Binding Sites,
pubmed-meshheading:9699644-Carcinoma, Squamous Cell,
pubmed-meshheading:9699644-Ceramides,
pubmed-meshheading:9699644-Combined Modality Therapy,
pubmed-meshheading:9699644-Drug Synergism,
pubmed-meshheading:9699644-Exotoxins,
pubmed-meshheading:9699644-Female,
pubmed-meshheading:9699644-Head and Neck Neoplasms,
pubmed-meshheading:9699644-Humans,
pubmed-meshheading:9699644-Mice,
pubmed-meshheading:9699644-Mice, Nude,
pubmed-meshheading:9699644-Mutation,
pubmed-meshheading:9699644-Neoplasm Transplantation,
pubmed-meshheading:9699644-Oligopeptides,
pubmed-meshheading:9699644-Protein Sorting Signals,
pubmed-meshheading:9699644-Radiation Tolerance,
pubmed-meshheading:9699644-Receptor, Epidermal Growth Factor,
pubmed-meshheading:9699644-Recombinant Fusion Proteins,
pubmed-meshheading:9699644-Transforming Growth Factor alpha,
pubmed-meshheading:9699644-Transplantation, Heterologous,
pubmed-meshheading:9699644-Tumor Cells, Cultured,
pubmed-meshheading:9699644-Tumor Suppressor Protein p53,
pubmed-meshheading:9699644-Virulence Factors
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pubmed:year |
1998
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pubmed:articleTitle |
Modulation of apoptotic response of a radiation-resistant human carcinoma by Pseudomonas exotoxin-chimeric protein.
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pubmed:affiliation |
Department of Radiation and Cellular Oncology, University of Chicago Hospitals, Illinois 60637, USA.
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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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