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
• Urinalysis methods   MeSH
• Smell physiology   MeSH
• Humans MeSH
• Prostatic Neoplasms diagnosis   urine   MeSH
• Dogs physiology   MeSH
• Sarcosine chemistry   urine   MeSH
• Sensitivity and Specificity MeSH
• Feasibility Studies MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Dogs physiology   MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Sarcosine 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
• Cell Cycle drug effects   physiology   MeSH
• Genes, Neoplasm physiology   MeSH
• Glycine N-Methyltransferase metabolism   MeSH
• Humans MeSH
• Mice, Inbred BALB C MeSH
• Mice, Nude MeSH
• Mice MeSH
• Cell Line, Tumor MeSH
• Prostatic Neoplasms metabolism   physiopathology   MeSH
• Polymerase Chain Reaction MeSH
• Gene Expression Regulation, Neoplastic drug effects   physiology   MeSH
• Sarcosine metabolism   pharmacology   MeSH
• Sarcosine Dehydrogenase metabolism   MeSH
• Transcriptome MeSH
• Neoplasm Transplantation MeSH
• Up-Regulation MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Retracted Publication MeSH
• Names of Substances
• Glycine N-Methyltransferase MeSH
• Sarcosine MeSH
• Sarcosine Dehydrogenase 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
• Models, Biological MeSH
• Phosphatidylethanolamines MeSH
• Folic Acid metabolism   MeSH
• Humans MeSH
• Liposomes * chemistry   ultrastructure   MeSH
• Metallothionein metabolism   MeSH
• Disease Models, Animal MeSH
• Antibodies, Monoclonal administration & dosage   MeSH
• Mice MeSH
• Cell Line, Tumor MeSH
• Prostatic Neoplasms drug therapy   metabolism   pathology   MeSH
• Sarcosine antagonists & inhibitors   chemistry   MeSH
• Tumor Burden drug effects   MeSH
• Dose-Response Relationship, Drug MeSH
• Xenograft Model Antitumor Assays MeSH
• Zinc metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• dioleoyl phosphatidylethanolamine MeSH Browser
• Phosphatidylethanolamines MeSH
• Folic Acid MeSH
• Liposomes * MeSH
• Metallothionein MeSH
• Antibodies, Monoclonal MeSH
• Sarcosine MeSH
• Zinc 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.

• Keywords
• lactate, metabolism, physical exercise, prostate-specific antigen, sarcosine,
• MeSH
• C-Reactive Protein analysis   MeSH
• Bicycling * MeSH
• Lactic Acid blood   MeSH
• Uric Acid blood   MeSH
• Middle Aged MeSH
• Humans MeSH
• Biomarkers, Tumor blood   urine   MeSH
• Prostatic Neoplasms blood   diagnosis   MeSH
• Prostate-Specific Antigen blood   MeSH
• Reproducibility of Results MeSH
• Sarcosine blood   urine   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• C-Reactive Protein MeSH
• Lactic Acid MeSH
• Uric Acid MeSH
• Biomarkers, Tumor MeSH
• Prostate-Specific Antigen MeSH
• Sarcosine 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
• Dextrans chemistry   ultrastructure   MeSH
• Humans MeSH
• Magnetite Nanoparticles chemistry   ultrastructure   MeSH
• Molecular Imaging methods   MeSH
• Antibodies, Monoclonal chemistry   immunology   MeSH
• Biomarkers, Tumor analysis   MeSH
• Cell Line, Tumor MeSH
• Prostatic Neoplasms chemistry   diagnosis   immunology   MeSH
• Nanocapsules chemistry   ultrastructure   MeSH
• Reproducibility of Results MeSH
• Fluorescence Resonance Energy Transfer methods   MeSH
• Sarcosine analysis   immunology   MeSH
• Sensitivity and Specificity MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Dextrans MeSH
• ferumoxtran-10 MeSH Browser
• Magnetite Nanoparticles MeSH
• Antibodies, Monoclonal MeSH
• Biomarkers, Tumor MeSH
• Nanocapsules MeSH
• Sarcosine MeSH