Document Detail


Tryptophan degradation in patients with gynecological cancer correlates with immune activation.
MedLine Citation:
PMID:  15896467     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Tryptophan degradation by the enzyme indoleamine-(2,3)-dioxy genase (IDO) and neopterin production are induced within cellular immune activation by stimulation of monocyte-derived macrophages and dendritic cells with cytokine interferon-gamma. Deprivation of tryptophan represents an important antimicrobial and antitumoral immune defence mechanism but it also suppresses T-cell proliferation. Recently tryptophan degradation by tumor cells was proposed as strategy to escape immune response. In this study the relationship between tryptophan degradation and immune activation was examined in 20 patients with gynecological cancer. Concentrations of tryptophan and kynurenine were measured by HPLC in sera of patients, and to estimate IDO activity, the kynurenine to tryptophan ratio was calculated. In parallel, neopterin concentrations were measured by ELISA. Tryptophan concentrations (median, interquartile range: 43.5, 31.2-56.3 microM) were lower in patients with gynecological cancer compared to healthy individuals of similar age (53.5, 47.0-64.2 microM; P<0.05). Kynurenine concentrations (median: 1.91 vs. 1.73 microM in controls) and kyn/trp (median: 41 vs. 35 micromol/mmol in controls) were slightly higher in patients, but not significantly different. Neopterin concentrations were significantly higher in patients (median: 10.8 vs. 7.0 nM in controls; P<0.05) and correlated with the kynurenine per tryptophan ratio (r(s)=0.555; P<0.02). In conclusion, tryptophan degradation is detectable in patients with gynecological cancer. The relationship between kyn/trp and neopterin concentrations indicates that cellular immune activation rather than tumor-mediated IDO-activity is responsible (228 words).
Authors:
Katharina Schroecksnadel; Christiana Winkler; Lothar C Fuith; Dietmar Fuchs
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2004-12-08
Journal Detail:
Title:  Cancer letters     Volume:  223     ISSN:  0304-3835     ISO Abbreviation:  Cancer Lett.     Publication Date:  2005 Jun 
Date Detail:
Created Date:  2005-05-17     Completed Date:  2005-07-21     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7600053     Medline TA:  Cancer Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  323-9     Citation Subset:  IM    
Affiliation:
Institute of Medical Chemistry and Biochemistry, Innsbruck Medical University, Fritz Pregl Strasse 3, A-6020 Innsbruck, Austria.
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MeSH Terms
Descriptor/Qualifier:
Adult
Age Factors
Case-Control Studies
Chromatography, High Pressure Liquid
Female
Genital Neoplasms, Female / immunology*,  physiopathology*
Humans
Immunity, Cellular*
Indoleamine-Pyrrole 2,3,-Dioxygenase
Kynurenine / blood*
Middle Aged
Neopterin / blood
Tryptophan / blood,  metabolism*
Tryptophan Oxygenase / pharmacology
Chemical
Reg. No./Substance:
343-65-7/Kynurenine; 670-65-5/Neopterin; 73-22-3/Tryptophan; EC 1.13.11.11/Tryptophan Oxygenase; EC 1.13.11.42/Indoleamine-Pyrrole 2,3,-Dioxygenase

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