Document Detail


Increased fatty acid synthase is a therapeutic target in mesothelioma.
MedLine Citation:
PMID:  11205903     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Many common human cancer tissues express high levels of fatty acid synthase (FAS), the primary enzyme for the synthesis of fatty acids, and the differential expression of FAS between normal and neoplastic tissues has led to the consideration of FAS as a target for anticancer therapy. To investigate the potential of targeting FAS for the treatment of pleural mesothelioma, we first determined whether FAS is overexpressed in human mesothelioma. By immunohistochemistry, we found 22 of 30 human mesothelioma tissue samples tested to express significantly increased levels of FAS compared with normal tissues, including mesothelium. To further explore FAS as a therapeutic target in mesothelioma, we established a nude mouse xenograft model for human mesothelioma using the H-Meso cell line. The i.p. xenografts of this cell line have high levels of FAS expression and fatty acid synthesis pathway activity and grow along mesothelial surfaces in a manner similar to the growth pattern of human mesothelioma. Growth of these tumor xenografts was essentially abolished in mice treated with weekly i.p. injections of C75, a synthetic, small molecule inhibitor of FAS, at levels that resulted in no significant systemic toxicity except for reversible weight loss. These results suggest that FAS may be an effective target for pharmacological therapy in a high proportion of human mesotheliomas.
Authors:
E W Gabrielson; M L Pinn; J R Testa; F P Kuhajda
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Clinical cancer research : an official journal of the American Association for Cancer Research     Volume:  7     ISSN:  1078-0432     ISO Abbreviation:  Clin. Cancer Res.     Publication Date:  2001 Jan 
Date Detail:
Created Date:  2001-02-01     Completed Date:  2001-03-22     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9502500     Medline TA:  Clin Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  153-7     Citation Subset:  IM    
Affiliation:
Department of Pathology and Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21224, USA.
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MeSH Terms
Descriptor/Qualifier:
4-Butyrolactone / analogs & derivatives*,  therapeutic use*
Animals
Antifungal Agents / pharmacology
Antineoplastic Agents / therapeutic use*
Cerulenin / pharmacology
Disease Models, Animal
Fatty Acid Synthetase Complex / antagonists & inhibitors*,  metabolism
Humans
Immunoenzyme Techniques
Mesothelioma / drug therapy*,  enzymology,  pathology
Mice
Mice, Nude
Neoplasm Transplantation
Neoplasms, Mesothelial / drug therapy*,  enzymology,  pathology
Paraffin Embedding
Prognosis
Tumor Cells, Cultured / cytology,  drug effects
Grant Support
ID/Acronym/Agency:
CA-06927/CA/NCI NIH HHS; CA-45745/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/4-methylene-2-octyl-5-oxofuran-3-carboxylic acid; 0/Antifungal Agents; 0/Antineoplastic Agents; 17397-89-6/Cerulenin; 96-48-0/4-Butyrolactone; EC 6.-/Fatty Acid Synthetase Complex

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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