title: Serum phenylalanine concentrations in patients with ovarian carcinoma correlate with concentrations of immune activation markers and of isoprostane-8.
abstract: Increased blood concentrations of essential amino acid phenylalanine are common in patients with HIV infection, in trauma and sepsis and in patients with cancer. The reason for this phenomenon is still unclear. However, all these clinical conditions are known to be linked with inflammation and immune activation. Oxidative stress resulting from chronic immune activation and inflammation could impair activity of phenylalanine (4)-hydroxylase (PAH) and thus give rise to increased phenylalanine concentrations. We therefore examined in 20 patients with ovarian cancer a possible association of serum concentrations of phenylalanine and tyrosine with immune activation markers 75 kDa soluble tumor necrosis factor-alpha receptor (sTNF-R75) and neopterin, and of oxidative stress marker isoprostane-8. Phenylalanine concentrations were higher in patients with higher FIGO stage and correlated with concentrations of sTNF-R75 (rs=0.441) and neopterin (rs=0.346; both p<0.05). No such correlations existed for tyrosine levels. The phenylalanine to tyrosine ratio (phe/tyr), an estimate of PAH activity, correlated somewhat stronger with sTNF-R75 (rs=0.549; p<0.01) and neopterin (rs=0.497; p=0.01). Finally, phenylalanine concentrations correlated with isoprostane-8 concentrations (rs=0.450, p=0.02). Correlations of phenylalanine and phe/tyr with immune activation markers point to a potential role of inflammation and immune activation in the accumulation of phenylalanine. The relationship between oxidative stress marker isoprostane-8 and phenylalanine as well as sTNF-R75 concentrations suggests a link between reactive oxygen species formed during chronic immune activation and inflammation and the decline of PAH activity, which might underlie the increase of phe/tyr (248 words).
authors.affiliation: Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Fritz Pregl Strasse 3, 6020 Innsbruck, Austria.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Neurauter
authors.forename: Anna V
authors.initials: AV
authors.lastname: Grahmann
authors.forename: Martin
authors.initials: M
authors.lastname: Klieber
authors.forename: Alain
authors.initials: A
authors.lastname: Zeimet
authors.forename: Maximilian
authors.initials: M
authors.lastname: Ledochowski
authors.forename: Barbara
authors.initials: B
authors.lastname: Sperner-Unterweger
authors.forename: Dietmar
authors.initials: D
authors.lastname: Fuchs
mesh_terms: D015415:Biomarkers / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D003536:Cystadenocarcinoma / Q000097:blood / Q000276:immunology / Q000473:pathology; D016889:Endometrial Neoplasms / Q000097:blood / Q000276:immunology / Q000473:pathology; D005260:Female; D015658:HIV Infections / Q000097:blood; D006801:Humans; D028421:Isoprostanes / Q000097:blood*; D008213:Lymphocyte Activation; D009367:Neoplasm Staging; D019798:Neopterin / Q000097:blood; D010051:Ovarian Neoplasms / Q000097:blood* / Q000276:immunology / Q000473:pathology; D018384:Oxidative Stress; D010649:Phenylalanine / Q000097:blood*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood; D018805:Sepsis / Q000097:blood; D014443:Tyrosine / Q000097:blood; D014594:Uterine Neoplasms / Q000097:blood / Q000276:immunology / Q000473:pathology
chemical_list: D015415:Biomarkers; D014408:Biomarkers, Tumor; D028421:Isoprostanes; D047889:Receptors, Tumor Necrosis Factor, Type II; D014443:Tyrosine; D010649:Phenylalanine; D019798:Neopterin