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Biomarkers in Cancer 2018Extracellular RNAs are gaining clinical interest as biofluid-based noninvasive markers for diseases, especially cancer. In particular, derivatives of transfer RNA (tRNA)...
Extracellular RNAs are gaining clinical interest as biofluid-based noninvasive markers for diseases, especially cancer. In particular, derivatives of transfer RNA (tRNA) are emerging as a new class of small-noncoding RNAs with high biomarker potential. We and others previously reported alterations in serum levels of specific tRNA halves in disease states including cancer. Here, we explored seminal fluid for tRNA halves as potential markers of prostate cancer. We found that 5' tRNA halves are abundant in seminal fluid and are elevated in prostate cancer relative to noncancer patients. Importantly, most of these tRNA halves are also detectable in prostatic tissues, and a subset were increased in malignant relative to adjacent normal tissue. These findings emphasize the potential of 5' tRNA halves as noninvasive markers for prostate cancer screening and diagnosis and provide leads for future work to elucidate a putative role of the 5' tRNA halves in carcinogenesis.
PubMed: 29497340
DOI: 10.1177/1179299X18759545 -
Prostate Cancer and Prostatic Diseases Sep 2017Extracellular vesicles (EVs) are a heterogeneous class of lipid bound particles shed by any cell in the body in physiological and pathological conditions. EVs play... (Review)
Review
BACKGROUND
Extracellular vesicles (EVs) are a heterogeneous class of lipid bound particles shed by any cell in the body in physiological and pathological conditions. EVs play critical functions in intercellular communication. EVs can actively travel in intercellular matrices and eventually reach the circulation. They can also be released directly in biological fluids where they appear to be stable. Because the molecular content of EVs reflects the composition of the cell of origin, they have recently emerged as a promising source of biomarkers in a number of diseases. EV analysis is particularly attractive in cancer patients that frequently present with increased numbers of circulating EVs.
METHODS
We sought to review the current literature on the molecular profile of prostate cancer-derived EVs in model systems and patient biological fluids in an attempt to draw some practical and universal conclusions on the use of EVs as a tool for liquid biopsy in clinical specimens.
RESULTS
We discuss advantages and limitations of EV-based liquid biopsy approaches summarizing salient studies on protein, DNA and RNA. Several candidate biomarkers have been identified so far but these results are difficult to apply to the clinic. However, the field is rapidly moving toward the implementation of novel tools to isolate cancer-specific EVs that are free of benign EVs and extra-vesicular contaminants. This can be achieved by identifying markers that are exquisitely present in tumor cell-derived EVs. An important contribution might also derive from a better understanding of EV types that may play specific functions in tumor progression and that may be a source of cancer-specific markers.
CONCLUSIONS
EV analysis holds strong promises for the development of non-invasive biomarkers in patients with prostate cancer. Implementation of modern methods for EV isolation and characterization will enable to interrogate circulating EVs in vivo.
Topics: Biomarkers, Tumor; Cell-Free Nucleic Acids; Extracellular Vesicles; Humans; Liquid Biopsy; Male; Neoplastic Cells, Circulating; Prostatic Neoplasms
PubMed: 28374743
DOI: 10.1038/pcan.2017.7 -
Disease Markers 2007Prostate cancer is a highly prevalent malignancy, which is clinically silent but curable while organ-confined. Because available screening methods show poor sensitivity... (Review)
Review
Prostate cancer is a highly prevalent malignancy, which is clinically silent but curable while organ-confined. Because available screening methods show poor sensitivity and specificity, the development of new molecular markers is warranted. Epigenetic alterations, mainly promoter hypermethylation of cancer-related genes, are common events in prostate cancer and might be used as cancer biomarkers. Moreover, the development of quantitative, high-throughput techniques to assess promoter methylation enabled the simultaneous screening of multiple clinical samples. From the numerous cancer-related genes hypermethylated in prostate cancer only a few proved to be strong candidates to become routine biomarkers. This small set of genes includes GSTP1, APC, RARbeta2, Cyclin D2, MDR1, and PTGS2. Single and/or multigene analyses demonstrated the feasibility of detecting early prostate cancer, with high sensitivity and specificity, in body fluids (serum, plasma, urine, and ejaculates) and tissue samples. In addition, quantitative hypermethylation of several genes has been associated with clinicopathologic features of tumor aggressiveness, and also reported as independent prognostic factor for relapse. The identification of age-related methylation at specific loci and the differential frequency of methylation among ethnical groups, also provided interesting data linking methylation and prostate cancer risk. Although large trials are needed to validate these findings, the clinical use of these markers might be envisaged for the near future.
Topics: Biomarkers, Tumor; Epigenesis, Genetic; Genetic Markers; Humans; Male; Prostatic Neoplasms
PubMed: 17325424
DOI: 10.1155/2007/356742 -
Cureus Nov 2020As the second most common cause of death amongst men in the United States, prostate cancer is a type of cancer that is known to develop and originate in the prostate... (Review)
Review
As the second most common cause of death amongst men in the United States, prostate cancer is a type of cancer that is known to develop and originate in the prostate gland. The main function of the prostate gland is to produce seminal fluid in which the sperm bathes. The seminal fluids are necessary for allowing the sperm to move easily through the urethra and also allows successful fertilization by providing an alkaline environment for the sperm in the acidic nature of the vagina. The seminal vesicles are two smaller glands that are attached to either side of the prostate gland and in radical prostatectomies, can get removed. In the event that the seminal vesicles are removed during a radical prostatectomy, the individual is unable to produce any seminal fluids and thus, becoming infertile. Prostate cancer is most commonly seen in patients over the age of 66 years, however, in the presence of predisposing risk factors, may occur as early as in the late 40s. Certain risk factors may speed the presentation of prostate cancer in individuals and thus, mandatory screening is recommended around the age of 45. If no risk factors are present, screening is recommended to begin after the age of 50 years. Screening for prostate cancer is focused on looking for prostate-specific antigen (PSA) in a blood test, though this may not be the most reliable method. The method of diagnosis stems from further testing done following an abnormal PSA test. A digital rectal examination and ultrasonography may also be used to assist with the diagnosis of prostate cancer. Though there are several different types of pharmaceutical interventions currently present in the eradication of prostate cancer, with androgen deprivation therapy being the most commonly used, surgical interventions may be utilized to completely resect cancer from an individual. Different radical prostatectomies are used; the appropriate approach utilized is dependent on the extensiveness of cancer and the type of cancer that is present.
PubMed: 33240734
DOI: 10.7759/cureus.11617 -
Asian Journal of Urology Apr 2015Benign prostatic hyperplasia (BPH) is a condition that occurs increasingly with age. The established gold standard treatment for BPH has been the electrocautery-based... (Review)
Review
Benign prostatic hyperplasia (BPH) is a condition that occurs increasingly with age. The established gold standard treatment for BPH has been the electrocautery-based transurethral resection of the prostate (TURP). TURP, however, is associated with several complications and side effects. Therefore, there is an increasing interest in a number of emerging minimally invasive therapies as alterative treatment options. Laser therapy using the Greenlight laser is a promising alternative to the traditional TURP. Selective absorption by hemoglobin allows rapid, hemostatic vaporization of prostate tissue. Additional advantages include avoidance or minimization of complications such as intraoperative fluid absorption, and bleeding, retrograde ejaculation, impotence, and incontinence, as well as its use in treating high volume BPH. We review the use of the Greenlight laser in the treatment of BPH, when comparing complications and advantages in relation to TURP.
PubMed: 29264127
DOI: 10.1016/j.ajur.2015.04.021 -
Journal of Immunology (Baltimore, Md. :... Mar 2013Prostate-specific Ag (PSA) is a serine protease that is expressed exclusively by normal and malignant prostate epithelial cells. The continued high-level expression of...
Prostate-specific Ag (PSA) is a serine protease that is expressed exclusively by normal and malignant prostate epithelial cells. The continued high-level expression of PSA by the majority of men with both high- and low-grade prostate cancer throughout the course of disease progression, even in the androgen-ablated state, suggests that PSA has a role in the pathogenesis of disease. Current experimental and clinical evidence suggests that chronic inflammation, regardless of the cause, may predispose men to prostate cancer. The responsibility of the immune system in immune surveillance and eventually tumor progression is well appreciated but not completely understood. In this study, we used a mass spectrometry-based evaluation of prostatic fluid obtained from diseased prostates after removal by radical prostatectomy to identify potential immunoregulatory proteins. This analysis revealed the presence of Igs and the complement system proteins C3, factor B, and clusterin. Verification of these findings by Western blot confirmed the high-level expression of C3 in the prostatic fluid and the presence of a previously uncharacterized C-terminal C3 cleavage product. Biochemical analysis of this C3 cleavage fragment revealed a putative PSA cleavage site after tyrosine-1348. Purified PSA was able to cleave iC3b and the related complement protein C5. These results suggest a previously uncharacterized function of PSA as an immunoregulatory protease that could help to create an environment hospitable to malignancy through proteolysis of the complement system.
Topics: Animals; Biomarkers, Tumor; Body Fluids; Cell Line; Complement C3b; Complement C5; Humans; Male; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Proteolysis; Semen; Serine Proteases; Sheep
PubMed: 23401592
DOI: 10.4049/jimmunol.1200856 -
Archivio Italiano Di Urologia,... Nov 2023Transurethral resection of the prostate (TURP) is the gold-standard for the treatment of benign prostate enlargement (BPE) associated with lower urinary tract symptoms...
INTRODUCTION
Transurethral resection of the prostate (TURP) is the gold-standard for the treatment of benign prostate enlargement (BPE) associated with lower urinary tract symptoms (LUTS), after failure of conservative therapy. At present, only resection-rate (grams of prostate resected over time) is regarded as an efficiency parameter to evaluate the skill of the operator and to assess the outcome of the procedure.
MATERIALS AND METHODS
Five surgeons performed TURP using a Gyrus-type bipolar system in 123 patients with BPE/LUTS who came to our observation from June 2016 to December 2019. The amount of irrigation fluid used during the procedure was registered and correlated to the operating time, resection-rate, prostate adenoma weight, post-operative bladder irrigation time, intraoperative bleeding and days of catheterization.
RESULTS
We found an inverse correlation between the amount of irrigation fluid used during TURP and the resection-rate recorded for all operators, according to Spearman's Correlation (r = -0.78, p = 0.002); a direct correlation was also found between the amount of irrigation fluid and the adenoma weight. Finally, we also found a direct correlation with intraoperative bleeding and the duration and amount of bladder irrigation during and after TURP.
CONCLUSIONS
The amount of irrigation fluid used is proposed as a reliable parameter to estimate the efficiency of the endoscopic procedure as well to assess the skill of the operator and shortterm results. The observed data encourage the possibility of applying this new efficiency indicator to all endoscopic maneuvers.
Topics: Male; Humans; Prostate; Transurethral Resection of Prostate; Urologic Surgical Procedures; Surgeons; Prostatic Hyperplasia; Lower Urinary Tract Symptoms; Adenoma
PubMed: 38193228
DOI: 10.4081/aiua.2023.11868 -
Journal of Extracellular Vesicles Feb 2022The isolation and subsequent molecular analysis of extracellular vesicles (EVs) derived from patient samples is a widely used strategy to understand vesicle biology and...
The isolation and subsequent molecular analysis of extracellular vesicles (EVs) derived from patient samples is a widely used strategy to understand vesicle biology and to facilitate biomarker discovery. Expressed prostatic secretions in urine are a tumor proximal fluid that has received significant attention as a source of potential prostate cancer (PCa) biomarkers for use in liquid biopsy protocols. Standard EV isolation methods like differential ultracentrifugation (dUC) co-isolate protein contaminants that mask lower-abundance proteins in typical mass spectrometry (MS) protocols. Further complicating the analysis of expressed prostatic secretions, uromodulin, also known as Tamm-Horsfall protein (THP), is present at high concentrations in urine. THP can form polymers that entrap EVs during purification, reducing yield. Disruption of THP polymer networks with dithiothreitol (DTT) can release trapped EVs, but smaller THP fibres co-isolate with EVs during subsequent ultracentrifugation. To resolve these challenges, we describe here a dUC method that incorporates THP polymer reduction and alkaline washing to improve EV isolation and deplete both THP and other common protein contaminants. When applied to human expressed prostatic secretions in urine, we achieved relative enrichment of known prostate and prostate cancer-associated EV-resident proteins. Our approach provides a promising strategy for global proteomic analyses of urinary EVs.
Topics: Extracellular Vesicles; Humans; Male; Mass Spectrometry; Prostate; Proteomics; Ultracentrifugation
PubMed: 35119778
DOI: 10.1002/jev2.12184 -
Frontiers in Endocrinology 2021Angiotensin-converting enzyme II (ACE2), a receptor for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) to enter host cells, is widely expressed in testes...
BACKGROUND
Angiotensin-converting enzyme II (ACE2), a receptor for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) to enter host cells, is widely expressed in testes and prostate tissues. The testis and prostate produce semen. At present, there are contradictory reports about whether SARS-CoV-2 can exist in the semen of infected men.
OBJECTIVE
To provide a comprehensive overview of the topic of whether COVID-19 can impact on male reproductive system.
METHODS
We reviewed the relevant publications on the possible impact of Coronavirus Disease 2019 (COVID-19) on male reproductive system and summarized the latest and most important research results so far. Literature published in English from December 2019 to January 31, 2021 regarding the existence of SARS-CoV-2 in semen, testis, and prostatic fluid and the effects of COVID-19 on male reproductive were included.
RESULTS
We identified 28 related studies, only one of which reported the presence of SARS-CoV-2 in semen. The study found that the semen quality of patients with moderate infection was lower than that of patients with mild infection and healthy controls. The impaired semen quality may be related to fever and inflammation. Pathological analysis of the testis/epididymis showed that SARS-CoV-2 viral particles were positive in 10 testicular samples, and the spermatogenic function of the testis was impaired. All 94 expressed prostatic secretion (EPS) samples were negative for SARS-CoV-2 RNA.
CONCLUSION
The likelihood of SARS-CoV-2 in the semen of COVID-19 patients is very small, and semen should rarely be regarded as a carrier of SARS-CoV-2 genetic material. However, COVID-19 may cause testicular spermatogenic dysfunction immune or inflammatory reactions. Long-term follow-up is needed for COVID-19 male patients and fetuses conceived during the father's infection period.
Topics: COVID-19; Genitalia, Male; History, 21st Century; Humans; Inflammation; Male; Prostate; SARS-CoV-2; Semen; Semen Analysis; Sexual Dysfunction, Physiological; Testis
PubMed: 34122351
DOI: 10.3389/fendo.2021.677701