Nejvíce citovaný článek - PubMed ID 23880848
Sarcosine as a potential prostate cancer biomarker--a review
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
- Názvy látek
- sarkosin MeSH
The effects of sarcosine on the processes driving prostate cancer (PCa) development remain still unclear. Herein, we show that a supplementation of metastatic PCa cells (androgen independent PC-3 and androgen dependent LNCaP) with sarcosine stimulates cells proliferation in vitro. Similar stimulatory effects were observed also in PCa murine xenografts, in which sarcosine treatment induced a tumor growth and significantly reduced weight of treated mice (p < 0.05). Determination of sarcosine metabolism-related amino acids and enzymes within tumor mass revealed significantly increased glycine, serine and sarcosine concentrations after treatment accompanied with the increased amount of sarcosine dehydrogenase. In both tumor types, dimethylglycine and glycine-N-methyltransferase were affected slightly, only. To identify the effects of sarcosine treatment on the expression of genes involved in any aspect of cancer development, we further investigated expression profiles of excised tumors using cDNA electrochemical microarray followed by validation using the semi-quantitative PCR. We found 25 differentially expressed genes in PC-3, 32 in LNCaP tumors and 18 overlapping genes. Bioinformatical processing revealed strong sarcosine-related induction of genes involved particularly in a cell cycle progression. Our exploratory study demonstrates that sarcosine stimulates PCa metastatic cells irrespectively of androgen dependence. Overall, the obtained data provides valuable information towards understanding the role of sarcosine in PCa progression and adds another piece of puzzle into a picture of sarcosine oncometabolic potential.
- MeSH
- buněčný cyklus účinky léků fyziologie MeSH
- geny nádorové fyziologie MeSH
- glycin-N-methyltransferasa metabolismus MeSH
- lidé MeSH
- myši inbrední BALB C MeSH
- myši nahé MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nádory prostaty metabolismus patofyziologie MeSH
- polymerázová řetězová reakce MeSH
- regulace genové exprese u nádorů účinky léků fyziologie MeSH
- sarkosin metabolismus farmakologie MeSH
- sarkosindehydrogenasa metabolismus MeSH
- transkriptom MeSH
- transplantace nádorů MeSH
- upregulace MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- odvolaná publikace MeSH
- Názvy látek
- glycin-N-methyltransferasa MeSH
- sarkosin MeSH
- sarkosindehydrogenasa MeSH
Herein, we describe the preparation of liposomes with folate-targeting properties for the encapsulation of anti-sarcosine antibodies (antisarAbs@LIP) and sarcosine (sar@LIP). The competitive inhibitory effects of exogenously added folic acid supported the role of folate targeting in liposome internalization. We examined the effects of repeated administration on mice PC-3 xenografts. Sar@LIP treatment significantly increased tumor volume and weight compared to controls treated with empty liposomes. Moreover, antisarAbs@LIP administration exhibited a mild antitumor effect. We also identified differences in gene expression patterns post-treatment. Furthermore, Sar@LIP treatment resulted in decreased amounts of tumor zinc ions and total metallothioneins. Examination of the spatial distribution across the tumor sections revealed a sarcosine-related decline of the MT1X isoform within the marginal regions but an elevation after antisarAbs@LIP administration. Our exploratory results demonstrate the importance of sarcosine as an oncometabolite in PCa. Moreover, we have shown that sarcosine can be a potential target for anticancer strategies in management of PCa.
- MeSH
- biologické modely MeSH
- fosfatidylethanolaminy MeSH
- kyselina listová metabolismus MeSH
- lidé MeSH
- liposomy * chemie ultrastruktura MeSH
- metalothionein metabolismus MeSH
- modely nemocí na zvířatech MeSH
- monoklonální protilátky aplikace a dávkování MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nádory prostaty farmakoterapie metabolismus patologie MeSH
- sarkosin antagonisté a inhibitory chemie MeSH
- tumor burden účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- xenogenní modely - testy protinádorové aktivity MeSH
- zinek metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- dioleoyl phosphatidylethanolamine MeSH Prohlížeč
- fosfatidylethanolaminy MeSH
- kyselina listová MeSH
- liposomy * MeSH
- metalothionein MeSH
- monoklonální protilátky MeSH
- sarkosin MeSH
- zinek MeSH
Herein, we present a study focused on the determination of the influence of long-distance (53 km) bicycle riding on levels of chosen biochemical urinary and serum prostate cancer (PCa) biomarkers total prostate-specific antigen (tPSA), free PSA (fPSA) and sarcosine. Fourteen healthy participants with no evidence of prostate diseases, in the age range from 49-57 years with a median of 52 years, underwent physical exercise (mean race time of 150 ± 20 min, elevation increase of 472 m) and pre- and post-ride blood/urine sampling. It was found that bicycle riding resulted in elevated serum uric acid (p = 0.001, median 271.76 vs. 308.44 µmol/L pre- and post-ride, respectively), lactate (p = 0.01, median 2.98 vs. 4.8 mmol/L) and C-reactive protein (p = 0.01, 0.0-0.01 mg/L). It is noteworthy that our work supports the studies demonstrating an increased PSA after mechanical manipulation of the prostate. The subjects exhibited either significantly higher post-ride tPSA (p = 0.002, median 0.69 vs. 1.1 ng/mL pre- and post-ride, respectively) and fPSA (p = 0.028, median 0.25 vs. 0.35 ng/mL). Contrary to that, sarcosine levels were not significantly affected by physical exercise (p = 0.20, median 1.64 vs. 1.92 µmol/mL for serum sarcosine, and p = 0.15, median 0.02 µmol/mmol of creatinine vs. 0.01 µmol/mmol of creatinine for urinary sarcosine). Taken together, our pilot study provides the first evidence that the potential biomarker of PCa-sarcosine does not have a drawback by means of a bicycle riding-induced false positivity, as was shown in the case of PSA.
- Klíčová slova
- lactate, metabolism, physical exercise, prostate-specific antigen, sarcosine,
- MeSH
- C-reaktivní protein analýza MeSH
- cyklistika * MeSH
- kyselina mléčná krev MeSH
- kyselina močová krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery krev moč MeSH
- nádory prostaty krev diagnóza MeSH
- prostatický specifický antigen krev MeSH
- reprodukovatelnost výsledků MeSH
- sarkosin krev moč MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- C-reaktivní protein MeSH
- kyselina mléčná MeSH
- kyselina močová MeSH
- nádorové biomarkery MeSH
- prostatický specifický antigen MeSH
- sarkosin MeSH
Herein, we describe an ultrasensitive specific biosensing system for detection of sarcosine as a potential biomarker of prostate carcinoma based on Förster resonance energy transfer (FRET). The FRET biosensor employs anti-sarcosine antibodies immobilized on paramagnetic nanoparticles surface for specific antigen binding. Successful binding of sarcosine leads to assembly of a sandwich construct composed of anti-sarcosine antibodies keeping the Förster distance (Ro) of FRET pair in required proximity. The detection is based on spectral overlap between gold-functionalized green fluorescent protein and antibodies@quantum dots bioconjugate (λex 400 nm). The saturation curve of sarcosine based on FRET efficiency (F₆₀₄/F₅₁₀ ratio) was tested within linear dynamic range from 5 to 50 nM with detection limit down to 50 pM. Assembled biosensor was then successfully employed for sarcosine quantification in prostatic cell lines (PC3, 22Rv1, PNT1A), and urinary samples of prostate adenocarcinoma patients.
- MeSH
- dextrany chemie ultrastruktura MeSH
- lidé MeSH
- magnetické nanočástice chemie ultrastruktura MeSH
- molekulární zobrazování metody MeSH
- monoklonální protilátky chemie imunologie MeSH
- nádorové biomarkery analýza MeSH
- nádorové buněčné linie MeSH
- nádory prostaty chemie diagnóza imunologie MeSH
- nanokapsle chemie ultrastruktura MeSH
- reprodukovatelnost výsledků MeSH
- rezonanční přenos fluorescenční energie metody MeSH
- sarkosin analýza imunologie MeSH
- senzitivita a specificita MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- dextrany MeSH
- ferumoxtran-10 MeSH Prohlížeč
- magnetické nanočástice MeSH
- monoklonální protilátky MeSH
- nádorové biomarkery MeSH
- nanokapsle MeSH
- sarkosin MeSH