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Molecular Cancer May 2016Prostate cancer, the second most frequently diagnosed cancer in males worldwide, is estimated to be diagnosed in 1.1 million men per year. Introduction of PSA testing... (Review)
Review
Prostate cancer, the second most frequently diagnosed cancer in males worldwide, is estimated to be diagnosed in 1.1 million men per year. Introduction of PSA testing substantially improved early detection of prostate cancer, however it also led to overdiagnosis and subsequent overtreatment of patients with an indolent disease. Treatment outcome and management of prostate cancer could be improved by the development of non-invasive biomarker assays that aid in increasing the sensitivity and specificity of prostate cancer screening, help to distinguish aggressive from indolent disease and guide therapeutic decisions. Prostate cancer cells release miRNAs into the bloodstream, where they exist incorporated into ribonucleoprotein complexes or extracellular vesicles. Later, cell-free miRNAs have been found in various other biofluids. The initial RNA sequencing studies suggested that most of the circulating cell-free miRNAs in healthy individuals are derived from blood cells, while specific disease-associated miRNA signatures may appear in the circulation of patients affected with various diseases, including cancer. This raised a hope that cell-free miRNAs may serve as non-invasive biomarkers for prostate cancer. Indeed, a number of cell-free miRNAs that potentially may serve as diagnostic, prognostic or predictive biomarkers have been discovered in blood or other biofluids of prostate cancer patients and need to be validated in appropriately designed longitudinal studies and clinical trials. In this review, we systematically summarise studies investigating cell-free miRNAs in biofluids of prostate cancer patients and discuss the utility of the identified biomarkers in various clinical scenarios. Furthermore, we discuss the possible mechanisms of miRNA release into biofluids and outline the biological questions and technical challenges that have arisen from these studies.
Topics: Biological Transport; Biomarkers, Tumor; Body Fluids; Disease Management; Extracellular Vesicles; Gene Expression Profiling; Genetic Testing; Humans; Male; MicroRNAs; Predictive Value of Tests; Prognosis; Prostatic Neoplasms; Transcriptome
PubMed: 27189160
DOI: 10.1186/s12943-016-0523-5 -
Translational Oncology Aug 2016Prostate cancer (PCa) is the most frequently diagnosed cancer and the second leading cause of cancer death among men in Western countries. Current screening techniques... (Review)
Review
Prostate cancer (PCa) is the most frequently diagnosed cancer and the second leading cause of cancer death among men in Western countries. Current screening techniques are based on the measurement of serum prostate specific antigen (PSA) levels and digital rectal examination. A decisive diagnosis of PCa is based on prostate biopsies; however, this approach can lead to false-positive and false-negative results. Therefore, it is important to discover new biomarkers for the diagnosis of PCa, preferably noninvasive ones. Metabolomics is an approach that allows the analysis of the entire metabolic profile of a biological system. As neoplastic cells have a unique metabolic phenotype related to cancer development and progression, the identification of dysfunctional metabolic pathways using metabolomics can be used to discover cancer biomarkers and therapeutic targets. In this study, we review several metabolomics studies performed in prostatic fluid, blood plasma/serum, urine, tissues and immortalized cultured cell lines with the objective of discovering alterations in the metabolic phenotype of PCa and thus discovering new biomarkers for the diagnosis of PCa. Encouraging results using metabolomics have been reported for PCa, with sarcosine being one of the most promising biomarkers identified to date. However, the use of sarcosine as a PCa biomarker in the clinic remains a controversial issue within the scientific community. Beyond sarcosine, other metabolites are considered to be biomarkers for PCa, but they still need clinical validation. Despite the lack of metabolomics biomarkers reaching clinical practice, metabolomics proved to be a powerful tool in the discovery of new biomarkers for PCa detection.
PubMed: 27567960
DOI: 10.1016/j.tranon.2016.05.004 -
Molecular Aspects of Medicine Apr 2020Numerous immunoassay based cancer biomarkers established in the 1970 and 1980'ies are widely used in clinical routine. Initial expectations of biomarkers such as CEA,... (Review)
Review
Numerous immunoassay based cancer biomarkers established in the 1970 and 1980'ies are widely used in clinical routine. Initial expectations of biomarkers such as CEA, CA125, CA19-9, AFP to provide decisive help in the diagnosis of early stage, pre-symptomatic cancers have not been realized. Thus, they are primarily used for monitoring disease progression and occasionally being useful as prognostic indicators. This limitation is due to the marker also being measurable in healthy individuals and frequently at elevated concentrations in common benign conditions. Most conventional tumor markers are glycosylated and interestingly specific alterations of the glycostructure part can often be seen early in the cancerous process. Conventional double monoclonal immunoassays are however blind to such changes as they are based on peptide epitope recognition. Wide selections of carbohydrate recognizing macromolecules, lectins, but also glycan structure recognizing antibodies are potentially useful for detecting such changes. Despite numerous attempts generating proof-of-principle evidence for this, such assays have generally not been successfully introduced into clinical routine. The affinity constants of lectin and glycan specific antibodies for their corresponding carbohydrate structures may be up to several orders too low to provide the detection limits and robustness expected from routine tumor markers. In this review, we describe an approach based on the use of highly fluorescent Eu-chelate dyed nanoparticles onto which lectins or glycan specific antibodies are coated to provide the necessary binding strength and signal amplification to provide low detection limits, while maintaining the original glycan-structure specificity. This concept applied to three markers, PSA, CA125 and CA15-3 provide glycoform assays of greatly enhanced cancer specificity using sample volumes similar or lower than corresponding traditional ELISAs. For ovarian cancer, we show that this new approach when applied to ovarian cyst fluid samples provide results similar to the performance obtained with ctDNA determinations of a set of 17 driver mutations and greatly superior compared to corresponding conventional immunoassays. Based on our results, we predict that the nanoparticle-lectin concept will enable a new generation of simple, low-cost biomarker assays of highly improved cancer specificity. Such tools should ideally be evaluated together with determination of ctDNA to establish early detection schemes for cancers e.g. ovarian, pancreas, lung where the detection rate of early stage disease is presently unacceptably low.
Topics: Biomarkers, Tumor; Breast Neoplasms; CA-125 Antigen; Circulating Tumor DNA; Europium; Female; Glycosylation; Humans; Immunoassay; Male; Membrane Proteins; Mucin-1; Nanoparticles; Ovarian Neoplasms; Polysaccharides; Prostate-Specific Antigen; Prostatic Neoplasms
PubMed: 31787337
DOI: 10.1016/j.mam.2019.11.001 -
Histochemistry and Cell Biology Jul 2019Prostate autonomic and sensory axons control glandular growth, fluid secretion, and smooth muscle contraction and are remodeled during cancer and inflammation....
Prostate autonomic and sensory axons control glandular growth, fluid secretion, and smooth muscle contraction and are remodeled during cancer and inflammation. Morphogenetic signaling pathways reawakened during disease progression may drive this axon remodeling. These pathways are linked to proliferative activities in prostate cancer and benign prostate hyperplasia. However, little is known about which developmental signaling pathways guide axon investment into prostate. The first step in defining these pathways is pinpointing when axon subtypes first appear in prostate. We accomplished this by immunohistochemically mapping three axon subtypes (noradrenergic, cholinergic, and peptidergic) during fetal, neonatal, and adult stages of mouse prostate development. We devised a method for peri-prostatic axon density quantification and tested whether innervation is uniform across the proximo-distal axis of dorsal and ventral adult mouse prostate. Many axons directly interact with or innervate neuroendocrine cells in other organs, so we examined whether sensory or autonomic axons innervate neuroendocrine cells in prostate. We first detected noradrenergic, cholinergic, and peptidergic axons in prostate at embryonic day (E) 14.5. Noradrenergic and cholinergic axon densities are uniform across the proximal-distal axis of adult mouse prostate while peptidergic axons are denser in the periurethral and proximal regions. Peptidergic and cholinergic axons are closely associated with prostate neuroendocrine cells whereas noradrenergic axons are not. These results provide a foundation for understanding mouse prostatic axon development and organization and, provide strategies for quantifying axons during progression of prostate disease.
Topics: Animals; Axons; Male; Mice; Mice, Inbred C57BL; Prostate
PubMed: 30976911
DOI: 10.1007/s00418-019-01784-6 -
Tumour Biology : the Journal of the... 2024Tumor markers (TMs) are a heterogeneous group of molecules used in the diagnosis, prognosis and follow-up of cancer patients. During neoplastic differentiation, cells... (Review)
Review
BACKGROUND
Tumor markers (TMs) are a heterogeneous group of molecules used in the diagnosis, prognosis and follow-up of cancer patients. During neoplastic differentiation, cells can either directly synthesize or induce the synthesis of TMs, and the release of these molecules into the bloodstream allows their quantification in biological fluids. Although very small concentrations of TMs are usually present in the serum or plasma of healthy subjects, increased concentrations may also be found in the presence of benign diseases or due to technical interference, producing false positive results.
MATERIAL AND METHODS AND RESULTS
Our review analyses the causes of false positives described between January 1970 to February 2023 for the TMs most frequently used in clinical practice: α-fetoprotein (AFP), β2-microglobulin (β2-M), cancer antigen 15-3 (CA 15-3), cancer antigen CA 19-9 (CA 19-9), cancer antigen CA 72-4 (CA 72-4), cancer antigen 125 (CA 125), carcinoembryonic antigen (CEA), chromogranin A (CgA), choriogonadotropin (hCG), cytokeratin 19 fragment (CYFRA 21-1), neuron-specific enolase (NSE), human epididymis protein 4 (HE4), serum HER2 (sHER2), squamous cell carcinoma antigen (SCCA), protein induced by vitamin K absence-II (PIVKA-II), Pro-gastrin-releasing peptide (Pro-GRP), prostate-specific antigen (PSA), Protein S-100 (S-100) and thyroglobulin (Tg). A total of 247 references were included.
CONCLUSIONS
A better understanding of pathophysiological processes and other conditions that affect the concentration of TMs might improve the interpretation of results and their clinical application.
Topics: Male; Humans; Biomarkers, Tumor; Lung Neoplasms; Antigens, Neoplasm; Keratin-19; Carcinoembryonic Antigen; Prostate-Specific Antigen; Phosphopyruvate Hydratase; CA-125 Antigen
PubMed: 38517826
DOI: 10.3233/TUB-220023 -
Clinica Chimica Acta; International... Oct 2019Liquid biopsy consists in the quantification and qualification of circulating cell-free DNA (cfDNA) and tumor-derived DNA (ctDNA) for cancer recognition. Recently, the...
BACKGROUND
Liquid biopsy consists in the quantification and qualification of circulating cell-free DNA (cfDNA) and tumor-derived DNA (ctDNA) for cancer recognition. Recently, the characterization of seminal cfDNA (scfDNA) has been reported as a possible biomarker for prostate cancer (PCa) diagnosis.
METHODS
Thirty patients with histologically proven PCa, 33 with benign prostate hyperplasia (BPH) and 21 healthy controls were enrolled. cfDNA was extracted from seminal fluid samples. cfDNA quantification and analysis were performed using Qubit ssDNA Kit and Agilent 2100 Bioanalyzer. Statistical analysis included: Levene's test, Shapiro-Wilk, Kolmogorov-Smirnov and Kruskal Wallis tests.
RESULTS
Median cfDNA was significantly higher in PCa patients 428.45 ng/mL (173.93-1159.62) compared to BPH patients 77.4 ng/mL (18.23-501) and healthy controls 25.4 ng/mL (15.37-76.62). scfDNA fragments longer than 1000 base-pairs were more common in patients with PCa compared to those with BPH and controls.
CONCLUSIONS
scfDNA concentration and fragment size differed significantly in the three groups of PCa, BPH and healthy controls. Both parameters are potential clinical biomarkers for PCa and can be used in both early diagnosis and follow-up. Using automated systems for high-throughput cfDNA quantification could improve the reproducibility of the method and facilitate the implementation of liquid biopsies in the clinical setting.
Topics: Aged; Biomarkers, Tumor; Cell-Free Nucleic Acids; Circulating Tumor DNA; Cohort Studies; Humans; Male; Middle Aged; Prostatic Neoplasms; Semen
PubMed: 31301282
DOI: 10.1016/j.cca.2019.07.011 -
Journal of Tropical Medicine 2023() could cause trichomoniasis through sexual transmission, which was globally distributed. In this study, the prevalence and phylogenetic analyses of among men in...
() could cause trichomoniasis through sexual transmission, which was globally distributed. In this study, the prevalence and phylogenetic analyses of among men in Xinxiang were conducted. From October 2018 to December 2019, a total of 634 male clinical samples were collected, including 254 samples of semen, 43 samples of prostate fluid, and 337 samples of urine. These samples were examined by nested PCR and a total of 32 (5.05%) -positive samples were detected. Among these samples, the positive rates of in semen, prostate fluid, and urine were 7.87% (20/254), 4.65% (2/43), and 2.97% (10/337), respectively. Three actin genes were successfully isolated and sequenced from the 32 positive DNA samples, and the analysis of the sequence and phylogenetic tree showed that the three actin gene sequences exhibited 99.7%-100% homology to the published actin gene sequence (EU076580) in NCBI, and the strains in the three positive samples were identified as genotype E. Our results demonstrate a notable genotype of in the male population and provide insight into the performance of these genetic markers in the molecular epidemiology of trichomoniasis. However, further studies are needed to research the association between the genotype and the pathogenicity of .
PubMed: 36895425
DOI: 10.1155/2023/4119956 -
BMC Urology Nov 2015Prostate cancer (PCa) is the most commonly diagnosed cancer and kills about 28,000 American men annually. Although progress has been made in understanding the molecular... (Review)
Review
BACKGROUND
Prostate cancer (PCa) is the most commonly diagnosed cancer and kills about 28,000 American men annually. Although progress has been made in understanding the molecular features of different forms of the disease, PCa is considered incurable when it becomes resistant to standard therapies. Prostate specific antigen (PSA) test has been a gold standard of diagnosis for PCa, however, it can result in lead to the unnecessary biopsies and treatment of indolent cancers due to the low specificity. Thus, the limitations of PSA screening for PCa have prompted much focus on strategies how to enhance the accuracy of PSA for distinction between aggressive and indolent cancers.
DISCUSSION
Studies of miRNAs in PCa patients have suggested differentially expressed miRNAs between healthy controls and those with PCa, providing potential biomarker candidates using body fluids including urine and blood. Virus infection has been considered to associate with PCa incidence. Virus infected PCa cells may shed extracellular vesicles and communicate with neighboring cells, which were not infected yet, however, no mechanistic approaches were performed to understand the biology. The miRNAs composition in the shedding extracellular vesicles, and its role in PCa are completely undefined. In the near future, new insights to connect between the viral derived miRNAs and PCa progression might provide an opportunity to diagnose, risk prediction and therapeutic strategies. The goal of this debate article is to provide a short review on miRNAs, virus infection and viral encoded miRNAs in PCa, with a primary focus on circulating miRNAs as potential non-invasive biomarkers for PCa patients.
Topics: Biomarkers, Tumor; Humans; Male; MicroRNAs; Papillomaviridae; Prostatic Neoplasms; RNA, Viral; Reproducibility of Results; Sensitivity and Specificity
PubMed: 26612689
DOI: 10.1186/s12894-015-0111-9 -
Arab Journal of Urology 2022To assess the efficacity and safety of using tranexamic acid (TXA) in the irrigation solution during transurethral resection of the prostate (TURP).
OBJECTIVE
To assess the efficacity and safety of using tranexamic acid (TXA) in the irrigation solution during transurethral resection of the prostate (TURP).
PATIENTS AND METHODS
A total of 50 patients undergoing TURP for benign prostatic hyperplasia were prospectively randomised in a controlled clinical trial and distributed into two groups. Group A received 0.1% TXA 1000 mg (10 mL) in 1 L of irrigation solution of sterile wash (glycine) during surgery, while Group B received 10 mL distilled water (placebo) in 1 L of irrigation solution of sterile wash (glycine) during surgery. At the end of surgery, a three-way catheter was inserted in the bladder. Group A received local 500 mg of TXA (5 mL), which was dissolved in 100 mL of normal saline solution, while Group B received distilled water (5 mL) dissolved in 100 mL of normal saline solution after which the catheter was clamped. The serum haemoglobin (Hb) concentration, haematocrit (HCT), blood loss volume, Hb concentration in the irrigation fluid, and bladder irrigation volumes were compared between the two groups at three time-points: preoperatively and at 4- and 24-h postoperatively. Coagulation function, complications, thromboembolic events, quality of endoscopic view, surgery duration, and hospital stay were also noted.
RESULTS
Group A had significantly lower blood loss intraoperatively, and at 4- and 24-h postoperatively compared to the control group ( < 0.05). The serum Hb concentration, HCT, Hb concentration in the irrigation fluid, and bladder irrigation volumes were significantly lower in the TXA group vs the control group ( < 0.001). The shortening of the surgery duration and improvement in the quality of the endoscopic view were significantly noted in the TXA group ( = 0.001). However, no thromboembolic events occurred in either group.
CONCLUSION
The use of TXA in the irrigation fluid during TURP and injection into the bladder postoperatively can reduce blood loss and the need for blood transfusion without increasing the risk of thrombosis.
PubMed: 35530564
DOI: 10.1080/2090598X.2022.2026011