Search

Urine is one of the diagnostically potential bio fluids, as it contains many metabolites and some of them are native fluorophores. These fluorophores distribution and the physiochemical properties may vary during any metabolic change or at different pathologic conditions. Since urine is a multicomponent fluid, synchronous luminescence technique, a powerful tool has been adopted to analyse multicomponents in single spectrum and to resolve emission spectrum without much of photobleaching of fluorophores. In this study, urine samples of both normal subjects and cancer patients were characterised using synchronous luminescence spectroscopy with a Stokes shift of 20 nm. Different ratio parameters were calculated from the intensity values of the synchronous luminescence spectra and they were used as input variables for a multiple linear discriminant analysis across normal and cancer groups. The stepwise linear discriminant analysis classifies 90.3% of the original grouped cases and 88.6% of the cross-validated grouped cases correctly.

Background: Biomarkers are good potential tools for early cancer diagnosis. Here we have analyzed eight different pteridines in the urine samples of cancer patients and compared them with samples from healthy subjects. Pteridines are important cofactors in the process of cell metabolism, and they have recently become a focal point of cancer screening research because certain pteridine levels have been shown to reflect the presence of cancers., Methods: We analyzed 8 pteridines; 6,7-dimethylpterin, 6-biopterin, d-(+)-neopterin, 6-hydroxymethylpterin, pterin, isoxanthopterin, xanthopterin and pterin-6-carboxylic acid using a house-built high-performance capillary electrophoresis with laser-induced fluorescence detection (HPCE-LIF). The levels of pteridines were reported as a ratio of pteridine to creatinine. Statistical hypothesis testing was conducted and P values were calculated to analyze the data., Results: Among the eight pteridines studied, 6-biopterin, 6-hydroxymethylpterin, pterin, xanthopterin, and isoxanthopterin levels were significantly higher in samples from cancer patients than in those from healthy subjects. Further, xanthopterin and isoxanthopterin levels were compared in breast cancer and lung cancer patients, but no significant difference was observed., Conclusion: Some pteridine levels can be used as biomarkers for noninvasive diagnosis of cancer; however, more data is needed to support this hypothesis., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Biological processes which might explain the association of pteridine excretion with proliferation are still unknown. Difficulties in the analysis and the determination of naturally occurring pteridines are described. The best quantitative estimations were achieved when measurement of non-reduced forms was attempted. The performance characteristics of such a method for neopterin by high performance liquid chromatography on reversed phase are given. Enhanced proliferation and dedifferentiation in cell cultures and organisms is paralleled by excretion of unconjugated pteridines into the medium or urine. Urinary neopterin in healthy subjects and in patients with benign diseases was only significantly raised in patients with viral diseases. However, an elevation of urinary neopterin occurred in a wide variety of malignant diseases. In haematologic neoplasias correlations of neopterin values to clinical features, to tumour staging, and to laboratory data were apparent. The clinical utility of neopterin measurement was also demonstrated in patients with gynaecologic tumors, particularly in patients with ovarian carcinoma. In both homogeneous patient groups the neopterin assay may provide an additional aid for prognosis and for monitoring therapy. Comparison of the neopterin assay with already established tumor marker substances at least revealed no inferiority in sensitivity. The present results justify extensive investigations in order to evaluate further the clinical applicability of the neopterin assay.

Neopterin is excreted at high levels during disease states challenging the T-lymphocyte-macrophage system. Stimulation of T-lymphocytes in mixed lymphocyte culture in the presence of macrophages is accompanied by raised neopterin levels in the supernatant. Neopterin may therefore be considered a specific indicator of cell-mediated immunity. Pretreatment analysis of patients with hemopoietic (191), urological (82) and gynecological (224) neoplasia revealed neopterin levels above the upper normal limits, with frequencies ranging from 57% (cervical carcinoma) to 96% (chronic lymphocytic leukemia). In patients with tumors of the genitourinary tract or with hemopoietic neoplasms, urinary neopterin levels were correlated with the tumor burden and became normal when remission was achieved. In gynecological cancer long term follow-up studies showed the value of neopterin excretion levels as a tumor marker. Tumor progression was indicated early by a rising neopterin level. Based on a comparison of different tumor types, the association of cell-mediated immunity and of neopterin excretion levels in less differentiated neoplasm is discussed.

Urinary pteridine concentrations in healthy control subjects and patients with cancer and non-malignant diseases were determined by HPLC and TLC after partial purification by ion exchange and Sephadex chromatography. Elevated concentrations of neopterin were found in 70% of the 50 cancer patients investigated. In patients with non-Hodgkin's lymphoma (seven cases) or with liver metastases (12 cases) neopterin concentrations were significantly higher than in control subjects (p < 0.01). Biopterin was less frequently increased (22%). Xanthopterin was generally raised when neopterin and/or biopterin excretion was high. Neopterin/biopterin ratios were higher in some patients with cancer or with severe renal insufficiency than in controls. These findings suggest that alterations in pteridine metabolism are common in malignant disease. The pathogenic, diagnostic and therapeutic significance of these changes remains to be established.

Heightened urinary concentrations of neopterin were detected in patients with malignant tumors. The levels of neopterin were quantified by high performance liquid chromatography. The normal range for male individuals was 280 +/- 1,7 ng neopterin/mg creatinin, for women 340 +/- 116 ng neopterin/mg creatinin. The values found in patients with malignant tumors were 1370 +/- 495 ng neopterin/mg creatinin and in patients with virus diseases 1637 +/- 696 ng neopterin/mg creatinin.

The incidence of elevated neopterin levels is presented for 748 patients with various malignancies. The mean urinary neopterin levels varied directly with stage and in patients with carcinoma of bladder according to histological grade of disease. In 178/208 patients with subsequent treatment for gynecological cancer, neopterin levels returned to normal within 3 weeks when tumor remission was achieved but remained high or even raised when persistent or recurrent cancer was later diagnosed. In 160 patients suffering from cervical carcinoma, significant differences in survival were demonstrated by Cox regression when patients were grouped according to their pretherapeutical neopterin level.