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Frontiers in Cell and Developmental... 2023Small extracellular vesicles (sEVs) are minute vesicles secreted by various cells that are capable of transporting cargo, including microRNAs, between donor and... (Review)
Review
Small extracellular vesicles (sEVs) are minute vesicles secreted by various cells that are capable of transporting cargo, including microRNAs, between donor and recipient cells. MicroRNAs (miRNAs), small non-coding RNAs approximately 22 nucleotides in length, have been implicated in a wide array of biological processes, including those involved in tumorigenesis. Emerging evidence highlights the pivotal role of miRNAs encapsulated in sEVs in both the diagnosis and treatment of urological tumors, with potential implications in epithelial-mesenchymal transition, proliferation, metastasis, angiogenesis, tumor microenvironment and drug resistance. This review provides a brief overview of the biogenesis and functional mechanisms of sEVs and miRNAs, followed by a summarization of recent empirical findings on miRNAs encapsulated in sEVs from three archetypal urologic malignancies: prostate cancer, clear cell renal cell carcinoma, and bladder cancer. We conclude by underscoring the potential of sEV-enclosed miRNAs as both biomarkers and therapeutic targets, with a particular focus on their detection and analysis in biological fluids such as urine, plasma, and serum.
PubMed: 37333986
DOI: 10.3389/fcell.2023.1192937 -
International Journal of Molecular... Mar 2019Prostate cancer is the most commonly diagnosed malignancy in men, claiming over350,000 lives worldwide annually. Current diagnosis relies on prostate-specific antigen... (Review)
Review
Prostate cancer is the most commonly diagnosed malignancy in men, claiming over350,000 lives worldwide annually. Current diagnosis relies on prostate-specific antigen (PSA)testing, but this misses some aggressive tumours, and leads to the overtreatment of non-harmfuldisease. Hence, there is an urgent unmet clinical need to identify new diagnostic and prognosticbiomarkers. As prostate cancer is a heterogeneous and multifocal disease, it is likely that multiplebiomarkers will be needed to guide clinical decisions. Fluid-based biomarkers would be ideal, andattention is now turning to minimally invasive liquid biopsies, which enable the analysis oftumour components in patient blood or urine. Effective diagnostics using liquid biopsies willrequire a multifaceted approach, and a recent high-profile review discussed combining multipleanalytes, including changes to the tumour transcriptome, epigenome, proteome, and metabolome.However, the concentration on genomics-based paramaters for analysing liquid biopsies ispotentially missing a goldmine. Glycans have shown huge promise as disease biomarkers, anddata suggests that integrating biomarkers across multi-omic platforms (including changes to theglycome) can improve the stratification of patients with prostate cancer. A wide range ofalterations to glycans have been observed in prostate cancer, including changes to PSAglycosylation, increased sialylation and core fucosylation, increased O-GlcNacylation, theemergence of cryptic and branched N-glyans, and changes to galectins and proteoglycans. In thisreview, we discuss the huge potential to exploit glycans as diagnostic and prognostic biomarkersfor prostate cancer, and argue that the inclusion of glycans in a multi-analyte liquid biopsy test forprostate cancer will help maximise clinical utility.
Topics: Biomarkers, Tumor; Exosomes; Glycosylation; Humans; Male; Polysaccharides; Prostate-Specific Antigen; Prostatic Neoplasms
PubMed: 30893936
DOI: 10.3390/ijms20061389 -
Biomolecular Concepts May 2017MicroRNAs (miRNAs) are non-coding small RNAs that are master regulators of genic expression and consequently of many cellular processes. But their expression is often... (Review)
Review
MicroRNAs (miRNAs) are non-coding small RNAs that are master regulators of genic expression and consequently of many cellular processes. But their expression is often deregulated in human tumors leading to cancer development. Recently miRNAs were discovered in body fluids (serum, plasma and others) and their levels have often been reported to be altered in patients. Circulating miRNAs became one of the most promising biomarkers in oncology for early diagnosis, prognosis and therapeutic response prediction. Here we describe the origins and roles of miRNAs, and summarize the most recent studies focusing on their usefulness as cancer biomarkers in lung, breast, colon, prostate, ovary cancers and melanoma. Lastly, we describe the main methodologies related to miRNA detection, which should be standardized for their use in clinical practice.
Topics: Biomarkers, Tumor; Early Detection of Cancer; Gene Expression Regulation, Neoplastic; Humans; MicroRNAs; Neoplasms
PubMed: 28448269
DOI: 10.1515/bmc-2017-0002 -
Oncology Letters Dec 2022Prostate cancer (PCa) is the second most frequently diagnosed solid tumor and the fifth leading cause of cancer mortality among men worldwide. The prostate specific...
Prostate cancer (PCa) is the second most frequently diagnosed solid tumor and the fifth leading cause of cancer mortality among men worldwide. The prostate specific antigen (PSA) test for PCa remains controversial. Therefore, the development of more effective non-invasive biomarkers for PCa is necessary. The present study evaluated the diagnostic value of microRNA (miR)-20b-5p in PCa. Tissue miR-20b-5p expression levels and their correlation with clinical parameters were assessed using The Cancer Genome Atlas (TCGA) datasets, and the diagnostic value of the miR-20b-5p expression levels in PCa tissues was assessed using receiver operating characteristic curve analysis. Reverse transcription-quantitative PCR (RT-qPCR) was used to assess the relative expression levels of miR-20b-5p in PCa tissues compared with benign prostate hyperplasia (BPH) tissues. In addition, miR-20b-5p expression levels in PCa cell lines and non-tumorigenic prostate epithelial cells were compared. In this study, exosomes were extracted from the prostatic fluid as a source of liquid biopsy for the detection of PCa. The prostatic fluid exosomal miR-20b-5p expression levels between patients with PCa and the biopsy-negative patients were compared, and the diagnostic efficiency of prostatic fluid exosomal miR-20b-5p expression levels in PCa was compared with PSA and with the European Randomized Study of Screening for Prostate Cancer (ERSPC) risk calculator. The mechanism by which miR-20b-5p may function in PCa was assessed using bioinformatic analysis and validation experiments. miR-20b-5p was expressed at a markedly higher level in PCa tissues compared with normal prostate tissues with high diagnostic efficiency (area under the curve: 0.826). The expression levels of miR-20b-5p were also significantly higher in PCa tissues compared with BPH tissues; similarly, miR-20b-5p was more highly expressed in PCa cells compared with non-tumorigenic prostate epithelial cells. Prostatic fluid exosomal miR-20b-5p expression levels in patients with PCa were significantly higher compared with confirmed to be biopsy-negative, and the diagnostic performance of miR-20b-5p was superior to PSA and ERSPC risk calculator. The results of RT-qPCR and western blotting following transfection of DU145 cells with miR-20b-5p mimics and inhibitor showed that miR-20b-5p reduced the expression of retinoblastoma-associated protein 1 (RB1). Therefore, RB1 may be a significant target gene for miR-20b-5p. In conclusion, the present study demonstrated that miR-20b-5p was upregulated in PCa at the tissue and cellular levels, as well as in prostatic fluid exosomes. Therefore, miR-20b-5p may be a promising early diagnostic biomarker for PCa and an important tool to guide the decision-making of prostate biopsy.
PubMed: 36311688
DOI: 10.3892/ol.2022.13546 -
Archivum Immunologiae Et Therapiae... Sep 2021Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), characterized by chronic pain in the perineum or lower abdomen regions, is a frequent disorder in men.... (Review)
Review
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), characterized by chronic pain in the perineum or lower abdomen regions, is a frequent disorder in men. Previous studies demonstrated that the immune mediators, including interleukin (IL)-1β, IL-6, interferon-γ, tumor necrosis factor-α, and immunoglobulins, are elevated in the expressed prostate secretions and seminal fluid of CP/CPPS men. The memory T, T helper 1 (Th1), Th17, and Th22 cells increase in the peripheral blood of CP/CPPS men. Additionally, prostate antigens specific-autoreactive T cells are identified in CP/CPPS patients. After generally reviewing and comparing the inflammatory responses in autoimmune diseases and CP/CPPS, we presumed that CP/CPPS is more likely to be defined as an autoimmune disease. Thus, a better understanding of autoimmune diseases would contribute to a deeper understanding of the CP/CPPS and provide new inspirations for the treatment of this disease.
Topics: Autoimmune Diseases; Chronic Disease; Chronic Pain; Humans; Male; Pelvic Pain; Prostatitis
PubMed: 34523016
DOI: 10.1007/s00005-021-00628-3 -
Cells Aug 2021The enlightenment of the formation of neutrophil extracellular traps (NETs) as a part of the innate immune system shed new insights into the pathologies of various... (Review)
Review
The enlightenment of the formation of neutrophil extracellular traps (NETs) as a part of the innate immune system shed new insights into the pathologies of various diseases. The initial idea that NETs are a pivotal defense structure was gradually amended due to several deleterious effects in consecutive investigations. NETs formation is now considered a double-edged sword. The harmful effects are not limited to the induction of inflammation by NETs remnants but also include occlusions caused by aggregated NETs (aggNETs). The latter carries the risk of occluding tubular structures like vessels or ducts and appear to be associated with the pathologies of various diseases. In addition to life-threatening vascular clogging, other occlusions include painful stone formation in the biliary system, the kidneys, the prostate, and the appendix. AggNETs are also prone to occlude the ductal system of exocrine glands, as seen in ocular glands, salivary glands, and others. Last, but not least, they also clog the pancreatic ducts in a murine model of neutrophilia. In this regard, elucidating the mechanism of NETs-dependent occlusions is of crucial importance for the development of new therapeutic approaches. Therefore, the purpose of this review is to address the putative mechanisms of NETs-associated occlusions in the pathogenesis of disease, as well as prospective treatment modalities.
Topics: Animals; Body Fluids; Embolism; Extracellular Traps; Humans; Inflammation; Neutrophils; Prospective Studies; Thrombosis
PubMed: 34571857
DOI: 10.3390/cells10092208 -
Molecular Cancer Apr 2017There is a growing trend towards exploring the use of a minimally invasive "liquid biopsy" to identify biomarkers in a number of cancers, including urologic... (Review)
Review
There is a growing trend towards exploring the use of a minimally invasive "liquid biopsy" to identify biomarkers in a number of cancers, including urologic malignancies. Multiple aspects can be assessed in circulating cell-free DNA, including cell-free DNA levels, integrity, methylation and mutations. Other prospective liquid biopsy markers include circulating tumor cells, circulating RNAs (miRNA, lncRNAs and mRNAs), cell-free proteins, peptides and exosomes have also emerged as non-invasive cancer biomarkers. These circulating molecules can be detected in various biological fluids, including blood, urine, saliva and seminal plasma. Liquid biopsies hold great promise for personalized medicine due to their ability to provide multiple non-invasive global snapshots of the primary and metastatic tumors. Molecular profiling of circulating molecules has been a stepping-stone to the successful introduction of several non-invasive multi-marker tests into the clinic. In this review, we provide an overview of the current state of cell-free DNA-based kidney, prostate and bladder cancer biomarker research and discuss the potential utility other circulating molecules. We will also discuss the challenges and limitations facing non-invasive cancer biomarker discovery and the benefits of this growing area of translational research.
Topics: Biomarkers, Tumor; Biopsy; Blood Proteins; DNA, Neoplasm; Exosomes; Humans; Mutation; Neoplastic Cells, Circulating; Peptides; Precision Medicine; RNA; Urologic Neoplasms
PubMed: 28410618
DOI: 10.1186/s12943-017-0644-5 -
Current Urology May 2016To investigate what clinical features typically present in transurethral resection (TUR) syndrome and to see which classically present first. The purpose of the study... (Review)
Review
OBJECTIVES
To investigate what clinical features typically present in transurethral resection (TUR) syndrome and to see which classically present first. The purpose of the study was to establish whether or not a particular method of anesthesia is preferred in detecting this syndrome in its early stages.
METHODS
A total of 1,502 transurethral resection of the prostate (TURP) over a 15 year period were reviewed to see which, if any, went on to experience this complication. Of these cases, 48 developed TUR syndrome. The case records were reviewed retrospectively and the presenting clinical features were analysed. All TURPs were routinely performed under spinal anesthesia and followed a standardised set up. The irrigation fluid used in all operations was Glycine 1.5%.
RESULTS
Forty eight patients displayed clinical features of TUR syndrome giving an incidence of 3.2%. Trainees of varying experience caused all but one case. Median resection time, resection weight and volume of intraoperative glycine irrigation fluid were 55 minutes (range 40-75 minutes), 44 grams (range 24-65 g), and 28 l (24-48 l) respectively. Only 16/48 TURPs had a recorded capsular perforation. Pre- vs. post-operative median hematocrit, hemoglobin and serum sodium were 0.42 vs. 0.33, 14.2 g/dl vs. 10.1 g/dl and 142 mmol/l vs. 121 mmol/l respectively. Patients presented with nausea 44/48, vomiting 28/48, visual disturbance 29/48, apprehension 37/48, disorientation 17/48, breathing difficulties 17/48, and bradycardia 19/21. The earliest observed sign was nausea 21/48, then bradycardia 11/48, apprehension 11/48, and visual disturbance 10/48; after which the procedure was abandoned. None of the patients developed stupor, coma or seizures. Out of the 48 patients, 9 were admitted to high dependency units and all of these were treated with IV furosemide. One patient required a blood transfusion. All patients recovered within 48 hours (range 18-48 hours) and none had any long term complications on follow up.
CONCLUSION
The features most associated with the early presentation of TUR syndrome require the patient to be conscious for detection. The use of spinal anaesthesia is therefore desirable to facilitate its early recognition.
PubMed: 27390576
DOI: 10.1159/000442854 -
Clinica Chimica Acta; International... Jan 2019Glycolytic enzymes are among the most frequently identified proteins in proteomics of exosomes/extracellular vesicles. This review brings up the possibility that... (Review)
Review
Glycolytic enzymes are among the most frequently identified proteins in proteomics of exosomes/extracellular vesicles. This review brings up the possibility that exosomes/extracellular vesicles during their life-time in bodily fluids power important energy-consuming functions by glycolytic conversion of glucose or fructose into ATP. It was seen that prostasomes (exosomes of the prostate) could produce ATP by glycolysis and that the produced ATP quickly was consumed by adjacent prostasomal ATPases. The glycolytic ATP production appeared to be coupled to self-sustaining energy requirements. It will also be discussed how a failure in this machinery (lowered activity of ATPases) with a resultant polluting leakage of extracellular ATP could affect cancer development.
Topics: Adenosine Triphosphatases; Adenosine Triphosphate; Energy Metabolism; Extracellular Vesicles; Humans; Neoplasms
PubMed: 30395864
DOI: 10.1016/j.cca.2018.10.044 -
American Journal of Cancer Research 2019Studies show that liquid biopsies are efficient in the detection of circulating cancer products. However, scientific community has not yet implemented this technology in... (Review)
Review
Studies show that liquid biopsies are efficient in the detection of circulating cancer products. However, scientific community has not yet implemented this technology in routine clinical practice. Liquid biopsies are less invasive than traditional surgical ones because they rely on the detection of specific biomarkers in readily accessible body fluid samples. The clinical management of prostate cancer depends on the controversial blood serum biomarker PSA (prostate specific antigen). PSA tests have a low accuracy. In addition, a positive PSA result for prostate cancer needs a confirmation through a tissue biopsy. Thus, liquid biopsies are considered tools to find a surrogate biomarker. This review aimed to show the landscape of liquid biopsies in prostate cancer research to understand its challenges and foresee the trends in this area. We performed an exhaustive Pubmed search of articles reporting the study of liquid biopsies in prostate cancer with circulating tumor cells, cell-free nucleic acids and extracellular vesicles as targets. After a thorough analysis, we retrieved sixty-two relevant articles. Among the identified articles, the most used target and body fluid were circulating tumor cells and blood, respectively. Enumeration of circulating tumor cells was the most reported parameter, but it was often combined with other biomarkers. The most used methods for biomarker detection were those based on transcriptome analysis. Despite the vast literature about liquid biopsy in prostate cancer, most studies seem to be stuck on improving the yield of technologies. Consequently, they seem to test a limited number of samples. Larger cohorts could provide robust evidence to translate liquid biopsies of prostate cancer to the clinics.
PubMed: 31392072
DOI: No ID Found