Cíl studie: V pilotním experimentu analyzovat metalothioneinu (MT) ve vzorcích moči pacientů se zhoubným nádorem prostaty (CaP). Metody: Vzorky byly analyzovány elektrochemicky metodou diferenční pulzní voltametrie (DPV) vBrdičkově základním elektrolytu. Získaná data byla vyhodnocena jako plochy pod křivkou (AUC). Koncentrace MT bylyvyhodnoceny metodou kalibrační křivky. Výsledky: Metallothioneiny jsou proteiny o molekulové hmotnosti kolem 10kDa. Jejich biologická role je především v udržování homeostázy iontů kovů v organismech. Analytické stanovení je komplikované. Mezi nejvhodnější metody patří elektrochemie. Uvedené metodické přístupy jsme aplikovali nasledování změn obsahu MT u pacientů s CaP a zbytnělou prostatou. V pilotním experimentu jsme zjistili, že průměrnáhladina MTu: a) kontrolní skupiny (n = 13) byla 2,9 ± 1,2 μg/mmol kreatininu; b) benigní hyperplazie prostaty 4,7 ± 1,7 μg/mmol kreatininu; c) CaP skupina (n = 9) 6,7 ± 1,5 μg/mmol kreatininu. Rozdíl mezi kontrolní skupinou a skupinouCaP byl statisticky průkazný (p = 0,0099). Mezi benigní hyperplazií prostaty a CaP byl také prokázán rozdíl (p =0,0928). Signály u pacientů s benigní hyperplazií prostaty (BHP) nevykazují statisticky významný rozdíl proti kontrolnískupině (p = 0,7869). Závěr: Získané prvotní výsledky naznačují, že hladiny MT lze v moči stanovit elektrochemicky. Mezi testovanými skupinami se podařilo prokázat rozdíly. Hladiny MT u pacientů s CaP byly zvýšené, ale musejí být dále detailněji studovány.
Aim: To analyse concentrations of metallothionein (MT) in urine samples of patients diagnosed with prostate cancer (CaP). Methods: Samples were electrochemically analysed by difference pulse voltametry (DPV) method in Brdička’s buffer. Acquired data were then evaluated as an area under the curve (AUC). Concentrations of MT were determinedby calibration curve method. Results: Metallothioneins are proteins with molecular weight about 10 kDa. Theirbiological significance lies in maintaining homeostasis of metal ions. Their analytical determination is complicated. One of the most effective determination methods is by electrochemistry. Previously mentioned methods were used tostudy the changes of MT concentrations of patients with CaP, and with benign prostate hyperplazia (BHP). Our pilotexperiment determined concentrations of MT in a) healthy controls (n = 13) was 2.9 ± 1.2 μg/mmol of creatinine, b) BHP was 4.7 ± 1.7 μg/mmol of creatinine, c) CaP group (n = 9) was 6.7 ± 1.5 μg/mmolof creatinine. Difference between healthy controls and CaP group was statistically significant (p = 0.0099). Differencebetween BHP and CaP group was also determined (p = 0.0928). Difference between BHP and healthy controls is notvery statistically significant (p = 0.7869). Conclusion: We were able to demonstrate differences between healthycontrols, BHP patients and CaP patients.Concentrations of MT in CaP patients were elevated, but they need to be studied in more detail.
Purpose: Prostate-specific antigen (PSA) is a sensitive but unspecific marker for prostate cancer (PC) detection, which may result in harms including overdiagnosis and overtreatment. Therefore, the development of new markers is of absolute value. The urinary level of engrailed-2 (EN2) protein has been recently suggested as a promising PC biomarker, correlating with tumour volume and stage. This study evaluated EN2 and its potential use in clinical practice.Materials and methods: Urinary EN2 was assessed by different commercially available enzyme-linked immunosorbent assay kits. The study sample included 90 patients with clinically localized PC compared to 30 healthy controls, and a group of 40 patients indicated for prostate biopsy due to an elevated PSA level where both pre- and post-digital rectal examination urine samples were collected.Results: No statistical difference between the patient group and the control group was obtained in all measured variables. There was no significant correlation between urinary EN2 and serum PSA, tumour staging and grading. Attentive DRE did not lead to significant changes of urinary EN2 or impact on its predictive power.Conclusions: Our results show that EN2 as a PC biomarker brings no additional value to the current use of PSA in clinical practice.
- MeSH
- analýza moči MeSH
- biopsie MeSH
- dospělí MeSH
- ELISA MeSH
- homeodoménové proteiny moč MeSH
- kalikreiny krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery krev moč MeSH
- nádory prostaty krev diagnóza patologie moč MeSH
- prediktivní hodnota testů MeSH
- prostatický specifický antigen krev MeSH
- proteiny nervové tkáně moč MeSH
- senioři MeSH
- staging nádorů MeSH
- studie případů a kontrol MeSH
- stupeň nádoru MeSH
- tumor burden MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
PURPOSE OF REVIEW: Prostate cancer (PCa) is the most commonly diagnosed cancer in men. Poor specificity and sensitivity of total PSA often results in over and sometimes underdetection/treatment. Therefore, more specific and sensitive biomarkers for the detection and monitoring especially of clinically significant PCa as well as treatment-specific markers are much sought after. In this field, urine has emerged as a promising noninvasive source of biomarkers. RECENT FINDINGS: RNA-based biomarkers are the most extensively studied type of urinary nucleic acids. ERG-Score/MiPS (Mi-Prostate Score) and SelectMDx might be considered as additional parameters together with clinical and imaging modalities to decrease unnecessary biopsies. miR Sentinel Tests could make it possible to accurately detect the presence of cancer and to distinguish low-grade from high-grade disease. In men with previous negative biopsies, PCA3 may suggest the need to repeat biopsy. SUMMARY: The definitive role of these markers and their clinical benefit needs future validation.
- MeSH
- analýza moči metody trendy MeSH
- antigeny nádorové moč MeSH
- biopsie MeSH
- lidé MeSH
- nádorové biomarkery moč MeSH
- nádory prostaty diagnóza moč MeSH
- prostata diagnostické zobrazování MeSH
- prostatický specifický antigen MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Sarcosine is an amino acid that is formed by methylation of glycine and is present in trace amounts in the body. Increased sarcosine concentrations in blood plasma and urine are manifested in sarcosinemia and in some other diseases such as prostate cancer. For this purpose, sarcosine detection using the nanomedicine approach was proposed. In this study, we have prepared superparamagnetic iron oxide nanoparticles (SPIONs) with different modified surface area. Nanoparticles (NPs) were modified by chitosan (CS), and sarcosine oxidase (SOX). SPIONs without any modification were taken as controls. Methods and Results: The obtained NPs were characterized by physicochemical methods. The size of the NPs determined by the dynamic light scattering method was as follows: SPIONs/Au/NPs (100⁻300 nm), SPIONs/Au/CS/NPs (300⁻700 nm), and SPIONs/Au/CS/SOX/NPs (600⁻1500 nm). The amount of CS deposited on the NP surface was found to be 48 mg/mL for SPIONs/Au/CS/NPs and 39 mg/mL for SPIONs/Au/CS/SOX/NPs, and repeatability varied around 10%. Pseudo-peroxidase activity of NPs was verified using sarcosine, horseradish peroxidase (HRP) and 3,3',5,5'-tetramethylbenzidine (TMB) as a substrate. For TMB, all NPs tested evinced substantial pseudo-peroxidase activity at 650 nm. The concentration of SPIONs/Au/CS/SOX/NPs in the reaction mixture was optimized to 0⁻40 mg/mL. Trinder reaction for sarcosine detection was set up at 510 nm at an optimal reaction temperature of 37 °C and pH 8.0. The course of the reaction was linear for 150 min. The smallest amount of NPs that was able to detect sarcosine was 0.2 mg/well (200 µL of total volume) with the linear dependence y = 0.0011x - 0.0001 and the correlation coefficient r = 0.9992, relative standard deviation (RSD) 6.35%, limit of detection (LOD) 5 µM. The suggested method was further validated for artificial urine analysis (r = 0.99, RSD 21.35%, LOD 18 µM). The calculation between the detected and applied concentrations showed a high correlation coefficient (r = 0.99). NPs were tested for toxicity and no significant growth inhibition was observed in any model system (S. cerevisiae, S. aureus, E. coli). The hemolytic activity of the prepared NPs was similar to that of the phosphate buffered saline (PBS) control. The reaction system was further tested on real urine specimens. Conclusion: The proposed detection system allows the analysis of sarcosine at micromolar concentrations and to monitor changes in its levels as a potential prostate cancer marker. The whole system is suitable for low-cost miniaturization and point-of-care testing technology and diagnostic systems. This system is simple, inexpensive, and convenient for screening tests and telemedicine applications.
- MeSH
- chitosan chemie MeSH
- Escherichia coli účinky léků růst a vývoj MeSH
- hemolýza účinky léků MeSH
- individualizovaná medicína MeSH
- koncentrace vodíkových iontů MeSH
- křenová peroxidasa chemie MeSH
- lidé MeSH
- limita detekce MeSH
- magnetické nanočástice chemie ultrastruktura MeSH
- nádorové biomarkery moč MeSH
- nádory prostaty diagnóza moč MeSH
- oxidace-redukce MeSH
- reprodukovatelnost výsledků MeSH
- Saccharomyces cerevisiae účinky léků růst a vývoj MeSH
- sarkosin moč MeSH
- sarkosinoxidasa chemie MeSH
- Staphylococcus aureus účinky léků růst a vývoj MeSH
- velikost částic MeSH
- železité sloučeniny chemie MeSH
- zlato chemie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Insufficient specificity and invasiveness of currently used diagnostic methods raises the need for new markers of urological tumors. The aim of this study was to find a link between the urinary excretion of amino acids and the presence of urological tumors. MATERIALS AND METHODS: Using ion-exchange chromatography, we tested urine samples of patients with prostate cancer (n=30), urinary bladder cancer (n=28), renal cell carcinoma (n=16) and healthy volunteers (control group; n=21). RESULTS: In each category, we found a group of amino acids which differed in concentration compared to the control group. These differences were most significant in sarcosine in patients with prostate cancer; leucine, phenylalanine and arginine in those with bladder cancer; and sarcosine, glutamic acid, glycine, tyrosine and arginine in the those with renal cell carcinoma. CONCLUSION: Results of our research imply a possible connection between the occurrence of specific types of amino acids in the urine and the presence of urological tumors.
- MeSH
- aminokyseliny moč MeSH
- chromatografie iontoměničová MeSH
- diferenciální diagnóza MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery * MeSH
- nádory ledvin diagnóza moč MeSH
- nádory močového měchýře diagnóza moč MeSH
- nádory prostaty diagnóza moč MeSH
- prostatický specifický antigen moč MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- senzitivita a specificita MeSH
- staging nádorů MeSH
- urologické nádory diagnóza moč MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
To date, there has been no evidence regarding the association between urinary sarcosine content and prostate cancer survival. Our main objective was to investigate whether levels of post-treatment urinary sarcosine are associated with relapse. The inclusion criteria were (in accordance with EAU 2017) as follows: histopathologically verified adenocarcinoma in prostate biopsy cores or specimens from transurethral resection of the prostate (TURP) or prostatectomy for benign prostatic enlargement (BPE) with retained ability to urinate. The median follow-up was 53 months. In the study, we retrospectively evaluated a cohort of 511 patients with prostate cancer with various risk factors and treatment strategies. Post-treatment sarcosine levels were elevated in 266 (52%) patients and highly elevated (≥200 nmol/L) in 71 (13%) patients. Urinary sarcosine content was significantly associated with number of relapses that patients experienced, P = 0.002 for sarcosine ≥200 vs ≤30 nmol/L. Multivariate analysis revealed that sarcosine was an independent predictor of recurrent relapses (≥2 relapses with an intermediate period of remission), HR = 3.89 (95% CI 1.29-11.7) for sarcosine >200 vs <30 nmol/L. This trend was even more pronounced in a subgroup of patients who underwent radical prostatectomy, HR = 3.29 (95% CI 1.06-10.18), where (single) relapse-free survival could also be predicted by sarcosine levels, HR = 1.96 (1.05-3.66). Urinary sarcosine may become a possible predictor for patients' outcomes, because patients with elevated post-treatment sarcosine could be predicted to have recurrent relapses of the disease.
- MeSH
- adenokarcinom chirurgie moč MeSH
- biologické markery moč MeSH
- hyperplazie prostaty chirurgie moč MeSH
- lidé MeSH
- lokální recidiva nádoru moč MeSH
- nádory prostaty chirurgie moč MeSH
- pooperační období MeSH
- prostatektomie MeSH
- recidiva MeSH
- retrospektivní studie MeSH
- sarkosin moč MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The hypothesis that dogs can detect malignant tumours through the identification of specific molecules is nearly 30 years old. To date, several reports have described the successful detection of distinct types of cancer. However, is still a lack of data regarding the specific molecules that can be recognized by a dog's olfactory apparatus. Hence, we performed a study with artificially prepared, well-characterized urinary specimens that were enriched with sarcosine, a widely reported urinary biomarker for prostate cancer (PCa). For the purposes of the study, a German shepherd dog was utilized for analyses of 60 positive and 120 negative samples. Our study provides the first evidence that a sniffer dog specially trained for the olfactory detection of PCa can recognize sarcosine in artificial urine with a performance [sensitivity of 90%, specificity of 95%, and precision of 90% for the highest amount of sarcosine (10 µmol/L)] that is comparable to the identification of PCa-diagnosed subjects (sensitivity of 93.5% and specificity of 91.6%). This study casts light on the unrevealed phenomenon of PCa olfactory detection and opens the door for further studies with canine olfactory detection and cancer diagnostics.
- MeSH
- analýza moči metody MeSH
- čich fyziologie MeSH
- lidé MeSH
- nádory prostaty diagnóza moč MeSH
- psi fyziologie MeSH
- sarkosin chemie moč MeSH
- senzitivita a specificita MeSH
- studie proveditelnosti MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- psi fyziologie MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND AND OBJECTIVES: Recently, we described an inverse association between cranberry supplementation and serum prostate specific antigen (PSA) in patients with negative biopsy for prostate cancer (PCa) and chronic nonbacterial prostatitis. This double blind placebo controlled study evaluates the effects of cranberry consumption on PSA values and other markers in men with PCa before radical prostatectomy. METHODS: Prior to surgery, 64 patients with prostate cancer were randomized to a cranberry or placebo group. The cranberry group (n=32) received a mean 30 days of 1500 mg cranberry fruit powder. The control group (n=32) took a similar amount of placebo. Selected blood/urine markers as well as free and total phenolics in urine were measured at baseline and on the day of surgery in both groups. Prostate tissue markers were evaluated after surgery. RESULTS: The serum PSA significantly decreased by 22.5% in the cranberry arm (n=31, P<0.05). A trend to down-regulation of urinary beta-microseminoprotein (MSMB) and serum gamma-glutamyltranspeptidase, as well as upregulation of IGF-1 was found after cranberry supplementation. There were no changes in prostate tissue markers or, composition and concentration of phenolics in urine. CONCLUSIONS: Daily consumption of a powdered cranberry fruit lowered serum PSA in patients with prostate cancer. The whole fruit contains constituents that may regulate the expression of androgen-responsive genes.
- MeSH
- adenokarcinom krev dietoterapie moč MeSH
- down regulace MeSH
- dvojitá slepá metoda MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery metabolismus MeSH
- nádory prostaty krevní zásobení dietoterapie moč MeSH
- oxidační stres fyziologie MeSH
- potravní doplňky MeSH
- předoperační péče MeSH
- prostatektomie metody MeSH
- prostatický specifický antigen metabolismus MeSH
- senioři MeSH
- Vaccinium macrocarpon * MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
Východiska: Nádory prostaty (prostate cancer – PC) tvoří heterogenní skupinu onemocnění s vysokou mírou prevalence, jenž v populaci západních zemí neustále stoupá. Od roku 1980 je pro sledování stavu nádorového onemocnění prostaty používáno stanovení prostatického specifického antigenu (PSA) v krevním séru následované dalšími diagnostickými postupy. Avšak relativní spolehlivost těchto vyšetření je vykoupena nepříjemným, invazivním poškozením tkáně. Proto se neustále hledají molekuly, které by mohly tyto stresové situace eliminovat a zvýšit tak záchyt PC nebo dokonce poskytnout informace o vývoji a průběhu onemocnění. V nynější době ukazují metabolomické a genomické studie, že některé biomolekuly mohou být využity pro zlepšení diagnosticko-prognostických možností a/nebo mohou být dokonce vhodným cílem pro vývoj nových terapeutických modalit. Jednou z těchto biomolekul je enzym glycin-N-metyltransferáza (GNMT), jenž hraje důležitou roli v biochemické konverzi glycinu na sarkosin. Souvislost této molekuly, ale také stejnojmenného genu, který ji kóduje (GNMT), s PC byla prokázána na několika úrovních a lze ji tak považovat za jeden ze slibných cílů pro návrh nových diagnosticko-prognostických přístupů. Cíl: Cílem práce je popsat fyziologickou roli a dále sumarizovat propojení mezi GNMT a PC, a to jak na úrovni genové struktury, genové exprese tohoto enzymu, tak na úrovni metabolizmu, který GNMT katalyzuje, čímž řídí nejen metylační status buňky, ale také metabolizmus kyseliny listové či methioninu. V neposlední řadě je též diskutována důležitost metylačních procesů v buňkách a souvislost mezi jejich aberacemi a rozvojem PC.
Background: Prostate cancer (PC) constitutes a heterogeneous group of diseases with high prevalence rates that are still increasing, particularly in western countries. Since 1980, prostate specific antigen (PSA) and other diagnostic approaches have been used for PC screening; however, some of these approaches are often deemed painful and cause invasive damage of tissue. Therefore, molecular approaches to PC diagnosis are attracting increasing attention, potentially providing patients with less stressful situations and providing better diagnoses and even prognostic information. Recent metabolomic and genomic studies have suggested that biomolecules can be used as diagnostic or prognostic markers or as targets for the development of novel therapeutic modalities. One of these molecules is glycine-N-methyltransferase (GNMT), an enzyme that plays a pivotal role in the biochemical conversion of glycine to sarcosine. The link between this molecule (encoded by homonymous gene – GNMT) and PC has been confirmed at several levels, and thus GNMT can be considered a promising target for the development of advanced diagnostic and/or prognostic approaches. Aim: The aim of this study was to analyse the physiological role of GNMT and to examine in greater detail its connection with PC at different levels, including gene structure, gene expression, and metabolism, in which GNMT plays an important role, not only in controlling the methylation status of cells, but also the metabolism of folic acid and methionine. Last but not least, we discuss the importance of cellular methylation processes and the link between their aberrations and PC development.
- MeSH
- glycin-N-methyltransferasa * fyziologie genetika metabolismus MeSH
- glycin metabolismus MeSH
- kyselina listová metabolismus MeSH
- lidé MeSH
- metylace DNA MeSH
- nádorové biomarkery genetika krev moč MeSH
- nádory prostaty * genetika krev moč MeSH
- sarkosin * metabolismus moč MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
Urinary metabolomic profiles have recently drawn a lot of attention owing to a debate regarding their possible role as potential clinical markers for prostate cancer. As was shown, amino acid metabolism in cancer patients differs from that in healthy people, and it can be thus utilized in early diagnostics. In this study, we monitored the behavior of potential noninvasive biomarker for prostate carcinoma, sarcosine, involved in the folate metabolism and DNA methylation processes, linked to the progression of prostate carcinoma. To obtain the maximum amount of information, the biochemical parameters (total protein, creatinine, ions, conductivity) were determined using spectrophotometry and electrochemistry. All results were subjected to statistical processing for revealing different correlations between the studied parameters. These metabolites were observed in the urine obtained from healthy subjects and influence of storage conditions (freezing and thawing) on the concentration of addition of sarcosine was monitored.
- MeSH
- časové faktory MeSH
- chromatografie iontoměničová * statistika a číselné údaje MeSH
- elektrochemické techniky statistika a číselné údaje MeSH
- lidé MeSH
- metabolomika MeSH
- nádorové biomarkery metabolismus moč MeSH
- nádory prostaty metabolismus moč MeSH
- odběr biologického vzorku * metody MeSH
- sarkosin * metabolismus moč MeSH
- teplota MeSH
- termodynamika MeSH
- zmrazování MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- hodnotící studie MeSH
- práce podpořená grantem MeSH