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      Evaluation of TKTL1 as a biomarker in serum of prostate cancer patients

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          Abstract

          Introduction

          Monocyte associated transketolase-like 1 (TKTL1) as a cancer biomarker has become popular with alternative practitioners, but plays no role in conventional medicine. This investigation evaluates the potential of serum TKTL1 as a biomarker for prostate cancer.

          Material and methods

          Patients (n = 66) undergoing curative radical prostatectomy (RPE) for biopsy-pro-ven PCa were included in the study. Controls (n = 10) were healthy, age-matched, male volunteers. 10 ml of peripheral blood was drawn from patients several days before surgery and from controls. Serum TKTL1 was measured using the ELISA method.

          Results

          The median age at tumor diagnosis was 66 years and median serum PSA was 8.0 ng/ml. Nearly 96% of PCas submitted to surgery were clinically significant. Compared to healthy controls, serum TKTL1 was significantly lower in PCa patients (p = 0.0001, effect size indicator r = Z/sqr(n) = 0.4179). No correlation was apparent between serum TKTL1 and serum PSA, Gleason sum, tumor stage or further clinical and pathologic parameters.

          Conclusions

          Reduced serum TKTL1 in PCa patients stands in opposition to TKTL1 epitope detection in monocytes (EDIM) based studies, whereby increased TKTL1 in monocytes of tumor patients has been reported. Since serum TKTL1 does not correlate with clinical parameters in the current investigation, further research is needed to clarify whether serum TKTL1 has potential as a biomarker for PCa.

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          Most cited references17

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          The economic burden of prostate cancer.

          In the present review we discuss expenditure on prostate cancer diagnosis, treatment and follow-up and evaluate the cost of prostate cancer and its management in different countries. Prostate cancer costs were identified from published data and internet sources. To provide up-to-date comparisons, costs were inflated to 2010 levels and the most recent exchange rates were applied. A high proportion of the costs are incurred in the first year after diagnosis; in 2006, this amounted to 106.7-179.0 million euros (€) in the European countries where these data were available (UK, Germany, France, Italy, Spain and the Netherlands). In the USA, the total estimated expenditure on prostate cancer was 9.862 billion US dollars ($) in 2006. The mean annual costs per patient in the USA were $10,612 in the initial phase after diagnosis, $2134 for continuing care and $33,691 in the last year of life. In Canada, hospital and drug expenditure on prostate cancer totalled C$103.1 million in 1998. In Australia, annual costs for prostate cancer care in 1993-1994 were 101.1 million Australian dollars. Variations in costs between countries were attributed to differences in incidence and management practices. Per patient costs depend on cancer stage at diagnosis, survival and choice of treatment. Despite declining mortality rates, costs are expected to rise owing to increased diagnosis, diagnosis at an earlier stage and increased survival. Unless new strategies are devised to increase the efficiency of healthcare provision, the economic burden of prostate cancer will continue to rise. © 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.
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            Use of prostate-specific antigen (PSA) isoforms for the detection of prostate cancer in men with a PSA level of 2-10 ng/ml: systematic review and meta-analysis.

            Measurement of serum prostate-specific antigen (PSA) for the detection of prostate cancer has poor specificity in men with PSA levels between 2 and 10 ng/ml. It has been suggested that measurement of the ratio of free to total PSA (f/tPSA) or complexed PSA (cPSA) might offer an improvement. We performed a systematic review and meta-analysis to evaluate the diagnostic performance of these tests among men with PSA levels between 2 and 10 ng/ml. Data on sensitivity and specificity were extracted from 66 eligible studies. Likelihood ratios and summary receiver operating characteristic curves were estimated and possible sources of heterogeneity between studies examined. Use of the f/tPSA or the cPSA test improved diagnostic performance among men with a total PSA (tPSA) of 2-4 or 4-10 ng/ml compared to tPSA alone. The diagnostic performance of the f/tPSA test was significantly higher in the tPSA range of 4-10 ng/ml compared to a tPSA range of 2-4 ng/ml (p < 0.01); at a sensitivity of 95%, the specificity was 18% in the 4-10 ng/ml tPSA range and 6% in the 2-4 ng/ml tPSA range. Among studies that measured both isoforms, the diagnostic performance of the f/tPSA test and the cPSA was equivalent in both PSA ranges. The use of the f/tPSA or cPSA test among men with PSA levels between 2 and 10 ng/ml can reduce the number of unnecessary biopsies whilst maintaining a high cancer detection rate.
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              Transketolase-like protein 1 (TKTL1) is required for rapid cell growth and full viability of human tumor cells.

              Cancer cells display high rates of aerobic glycolysis, a phenomenon known as the Warburg effect. Lactate and pyruvate, the end products of glycolysis, are overproduced by cancer cells even in the presence of oxygen. The pentose phosphate pathway (PPP) allows glucose conversion to ribose for nucleic acid synthesis, glucose degradation to lactate, and regeneration of redox equivalents. The nonoxidative part of the PPP is controlled by transketolase (TKT) enzymes. One TKT isoform, the transketolase-like protein 1 (TKTL1) is specifically upregulated in different human cancers and its overexpression predicts a poor patient's survival. This finding implicates that an increased TKTL1 expression may activate the PPP leading to enhanced cancer cell growth and survival. To analyze the functional role of TKTL1 in malignant progression, we inhibited TKTL1 by RNAi technologies in human HCT116 colon carcinoma cells. TKTL1 suppression resulted in a significantly slowed cell growth, glucose consumption and lactate production. In TKTL1 knockdown-cells, the intracellular reactive oxygen species levels were not significantly increased, whereas the sensitivity towards oxidative stress-induced apoptosis was clearly enhanced. These data provide new clues on the importance of TKTL1 dys-regulation in tumor cells and indicate that TKTL1 overexpression may be considered not only as a new tumor marker but also as a good target for anticancer therapy.
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                Author and article information

                Journal
                Cent European J Urol
                Cent European J Urol
                CEJU
                Central European Journal of Urology
                Polish Urological Association
                2080-4806
                2080-4873
                30 June 2016
                2016
                : 69
                : 3
                : 247-251
                Affiliations
                [1 ]Mainz University Medical Center, Department of Urology, Mainz, Germany
                [2 ]University Hospital Frankfurt, Department of Urology, Frankfurt, Germany
                [3 ]University Hospital Frankfurt, Department of Surgery, Frankfurt, Germany
                [4 ]University Hospital Frankfurt, Department of Vascular and Endovascular Surgery, Frankfurt, Germany
                [5 ]University Hospital Frankfurt, Department of Laboratory Medicine, Frankfurt, Germany
                [6 ]Vitalicum Urology Outpatient Unit, Frankfurt, Germany
                [* ]contributed equally as senior authors
                Author notes
                Corresponding author Igor Tsaur, University Medicine Mainz, Department of Urology, Langenbeckstr. 1, 55131 Mainz, Germany. phone: +49 613 1172 041. igor.tsaur@ 123456unimedizin-mainz.de
                Article
                00820
                10.5173/ceju.2016.820
                5057049
                27729989
                fa796c10-8f76-4029-acea-fdd6c5a518dc
                Copyright by Polish Urological Association

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License, allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.

                History
                : 23 March 2016
                : 24 April 2016
                : 05 June 2016
                Categories
                Original Paper

                complementary medicine,prostate cancer,diagnosis,biomarker,tktl1

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