Chapter 12 Serum Nucleoside Chromatography for Classification of Lung Cancer Patients and Controls

McEntire, John E.; Kuo, Kenneth C.; Smith, Mark E.; Stalling, David L.; Richens, Jack W.; Zumwalt, Robert W.; Gehrke, Charles W.; Papermaster, Ben W.

doi:10.1016/s0301-4770(08)61550-x

Cited by 4 publications

(7 citation statements)

References 21 publications

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“…Advantages of pseudouridine as a marker of RNA turnover rate in comparison with other modified nu- cleosides are its approximately 100-fold greater concentration in blood plasma, and its lesser variability attributable to the renal clearance rate, sex-related differences, genetic influences or environmental conditions (19). There are only a'few reports indicating the elevation of serum pseudouridine concentrations in patients suffering from neoplastic diseases (5,17,20,21).…”

Section: Introductionmentioning

confidence: 99%

Blood Plasma Pseudouridine in Patients with Malignant Proliferative Diseases

Motyl¹,

Traczyk²,

Cieśluk³

et al. 1993

Clinical Chemistry and Laboratory Medicine

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The blood plasma concentration of pseudouridine was estimated in 104 healthy adult subjects, and 108 patients suffering from malignant proliferative diseases. The HPLC method for simultaneous determination of pseudouridine and creatinine was applied.The average physiological concentration of pseudouridine in blood plasma was 2.43 ± 0.97 μπιοί -I" 1 or 29.15 + 7.40 mmol · mol" 1 creatinine. The physiological urinary excretion of pseudouridine was 14.32 ± 5.20 μπιοί -24h" 1 · kg~°· 75 or 19.60 + 5.22 mmol -mol" 1 creatinine. Renal clearance of pseudouridine and endogenous creatinine were 4.04 + 0.99 and 5.50 ± 1.46ml -kg" 075 , respectively. A positive correlation (r = 0.55, P < 0.01) was found between age (in the range 20 -92 years) and blood plasma pseudouridine concentration (μιηοΐ · I" 1 ). By expressing plasma pseudouridine in relation to plasma creatinine, the apparent influence of non-metabolic factors (age, renal insufficiency, blood dilution) on the plasma pseudouridine concentration were largely excluded.Among haematological proliferative diseases the highest values of plasma pseudouridine concentrations were observed in chronic lymphocytic leukaemia (8.19 μπιοί-I" 1 ; 54.9 mmol -mol"" 1 creatinine) and multiple myeloma (7.02 μπιοί · I" 1 ; 52.5 mmol · mol~J creatinine). In multiple myeloma, but not in chronic lymphocytic leukaemia, the plasma pseudouridine concentration depended on the clinical stage. A lower, but still significant response in non^Hodgkin's lymphoma was noted (4.03 μπιοί · I" 1 ; 40.88 mmol · mol" 1 creatinine).A significant increase of the plasma pseudouridine concentration was characteristic of adenocarcinomas of the large intestine, and it occurred in the early stages of malignant growth. In patients with lung cancer the plasma pseudouridine concentration was elevated only in advanced cases with metastases. The increased pseudouridine concentration was evident in all examined cancers of the urogenital system: cancer of the urinary bladder, cancer of the kidney, cancer of the prostate, and cancer of the testis.It is concluded that the determination of pseudouridine in blood plasma, particularly in relation to creatinine, is a valuable biochemical m rker of accelerated turnover rate of nucleic acids associated with neoplastic growth. ') This study was supported by a grant from the Ministry of National Education.

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Section: Introductionmentioning

confidence: 99%

Blood Plasma Pseudouridine in Patients with Malignant Proliferative Diseases

Motyl¹,

Traczyk²,

Cieśluk³

et al. 1993

Clinical Chemistry and Laboratory Medicine

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“…Several authors [31][32][33][34][35] thought that serum analysis would offer distinct advantages compared to urine, 1) nucleoside levels of cancer patients and normal subjects can be directly compared in concentration terms without relationship to creatinine and other metabolites; 2) serum nucleosides may be subject to fewer structural alterations than urinary nucleosides; 3) ease of collection and physician preferences for serum values for other analyses favor serum. The disadvantages are the concentrations of the modified nucleosides in serum are ca.…”

Section: Resultsmentioning

confidence: 99%

“…Urinary levels of modified nucleosides have been also suggested to be useful for monitoring progress of disease and response to therapy [9, 10, 15-17, 28 30]. Promising results from these studies on the urinary nucleosides stimulated interest on investigations for a larger number of nucleosides, especially for nucleosides in serum [8,[31][32][33][34][35].…”

Section: Introductionmentioning

confidence: 99%

Study of normal and modified nucleosides in serum by RP-HPLC

Enderle

Liebich

et al. 2000

Chromatographia

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KeyWordsColumn liquid chromatography Nucleosides in serum Tumor markers Factor analysis SummaryModified nucleosides derived predominantly from transfer ribonucleic acid (tRNA) have been studied as possible tumor markers. In this paper a reversed-phase high-performance liquid chromatographic (RP-HPLC) method has been applied to study 15 normal and modified nucleosides in serum. The nucleoside levels in normal human serum were established, and the concentrations of 15 nucleosides in serum from 19 cancer patients were determined. It was found that the concentrations of modified nucleosides were significantly higher in patient sera. Based on 15 nucleoside concentrations in serum, factor analysis could classify correctly 90~ of cancer patients from the normal humans. Furtherwork showed that urine was slightly better than serum when determining nucleosides as biological marker candidates. More work is ongoing to determine the clinical usefulness of modified nucleosides as tumor markers.

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“…It is important from the analytical point of view ( Table 2). Analysis of nucleosides and their modified derivatives by HPLC requires the use of buffers or acidic additives to the mobile phase to improve peak shape, resolution and sensitivity [10][11][12][13][14]. Application of UHPLC provides better peak shapes and shorter chromatographic runs without the utilization of any Table 2 The asymmetry values f AS (appointed in 10% of peak height) for several different mobile phase compositions and all columns used in the study (C1, C2, C3, C4, C5) determined for 1-methylguanosine.…”

Section: Peak Asymmetrymentioning

confidence: 99%

“…Over 60 years it has been shown abnormal amounts of these compounds in urine are markers of diseases, such as Alzheimer's disease, tumors or AIDS. Increased quantities of some of modified nucleosides were excreted in the urine of patients with breast cancer [4][5][6], thyroid cancer [7], head and neck cancer [8], bladder cancer [9], kidney cancer [10], leukemia and lymphoma [11], cancer of the lung [12] and liver cancer [13].…”

Section: Introductionmentioning

confidence: 99%