Modified nucleosides: an accurate tumour marker for clinical diagnosis of cancer, early detection and therapy control

Abstract

Modified nucleosides, regarded as indicators for the whole-body turnover of RNAs, are excreted in abnormal amounts in the urine of patients with malignancies. To test their usefulness as tumour markers and to compare them with the conventional tumour markers, fractionated urine samples were analysed using chromatography. The excretion patterns of nucleosides of 68 cancer patients with malignant and benign tumours and 41 healthy controls have been studied. Significant elevations in the total sum and the concentrations of at least three (or four) of indicator nucleosides cytidine, pseudouridine, 2-pyridone-5-carboxamide-N1-ribofuranoside, N2,N2-dimethylguanine, 1-methylguanosine, 2-methylguanosine and 1-methyladenosine indicate a tumour with a sensitivity of 54% (77%) and a specificity of 86% (98%). Using an artificial neural network analysis, a sensitivity of 97% and a specificity of 85% were achieved in differentiating between tumour and control volunteers. The comparison with carcinoembryonic antigen, cancer antigen 15-3 und tissue polypeptide antigen indicates that urinary nucleosides may be useful tumour markers. This study suggests that the simultaneous determination of modified nucleosides and creatinine in urine samples of patients with cancer leads to an advantage to current methods and is a useful method to detect cancer early and to control the success of therapy.

Evaluation of molecularly imprinted polymers using 2′,3′,5′-tri-O-acyluridines as templates for pyrimidine nucleoside recognition

“…and MIP-4, the difference in alkyl chain length in the triester templates (3,4) does not appear to influence the binding capacities of these polymers; there is an obvious difference observed for MIP-2, where a smaller triacetyl ester was used as the template. Compared to the other MIPs, on MIP-2, a higher average affinity of 1.7×10 4 M −1 was obtained for the template, along with a doubling of the number of binding sites observed.…”

“…The testing was Fig. 1 Targeted molecule uridine (1) and its "dummy" templates (2-4) with the selected 2,6 bisacrylamidopyridine (BAAPy) functional monomer (5) performed by raising the concentration of the templates (2)(3)(4) in 1 mL of solvent and subsequently mixing, until precipitation was observed. The mass concentration (mg mL −1 ) was converted accordingly to molar concentration (mmol L −1 ) for each template (Fig.…”

“…Some analogues represent therapeutic cornerstones of various severe human pathogens [1], meanwhile other, naturally modified nucleosides are produced by the degradation of nucleic acids and are potential tumour markers [2,3]. Among them, pyrimidine nucleosides (such as troxacitabine, sapacitabine, CP-4055, 3′-ethynylcytidine and 5-azapyrimidines) [4] are clinically important anticancer drugs used especially in the treatment of solid tumours [5].…”

Molecularly imprinted polymers for solid-phase extraction of 1-methyladenosine from human urine

“…The levels of modified nucleosides excreted in the human urine have been shown to be related with the progression of a number of different cancer types [1,2]. Ribonucleic acid (RNA), particularly transfer RNA, is a primary source of modified nucleosides found in the urine [3].…”

Molecular Identification of Pseudouridine-metabolizing Enzymes

“…Pseudouridine metabolism is likely to be restricted to only some species. The finding that this nucleoside is present in human urine, where its concentration is increased in tumor-bearing patients (9,10), suggests that pseudouridine is not metabolized in man.…”