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Frontiers in Oncology 2021Prostate Cancer (PCa) is the most commonly diagnosed malignancy and second leading cause of cancer-related mortality in men. With the use of next generation sequencing... (Review)
Review
Prostate Cancer (PCa) is the most commonly diagnosed malignancy and second leading cause of cancer-related mortality in men. With the use of next generation sequencing and proteomic platforms, new biomarkers are constantly being developed to both improve diagnostic sensitivity and specificity and help stratify patients into different risk groups for optimal management. In recent years, it has become well accepted that altered glycosylation is a hallmark of cancer progression and that the glycan structures resulting from these mechanisms show tremendous promise as both diagnostic and prognostic biomarkers. In PCa, a wide range of structural alterations to glycans have been reported such as variations in sialylation and fucosylation, changes in branching, altered levels of Lewis and sialyl Lewis antigens, as well as the emergence of high mannose "cryptic" structures, which may be immunogenic and therapeutically relevant. Furthermore, aberrant expression of galectins, glycolipids, and proteoglycans have also been reported and associated with PCa cell survival and metastasis. In this review, we discuss the findings from various studies that have explored altered and linked glycosylation in PCa tissue and body fluids. We further discuss changes in -GlcNAcylation as well as altered expression of galectins and glycoconjugates and their effects on PCa progression. Finally, we emphasize the clinical utility and potential impact of exploiting glycans as both biomarkers and therapeutic targets to improve our ability to diagnose clinically relevant tumors as well as expand treatment options for patients with advanced disease.
PubMed: 35004332
DOI: 10.3389/fonc.2021.809170 -
Journal of Cancer 2020Two decades ago a class of ion channels, hitherto unsuspected, was discovered. In mammals these Transient Receptor Potential channels (TRPs) have not only expanded in... (Review)
Review
Two decades ago a class of ion channels, hitherto unsuspected, was discovered. In mammals these Transient Receptor Potential channels (TRPs) have not only expanded in number (to 26 functional channels) but also expanded the view of our interface with the physical and chemical environment. Some are heat and cold sensors while others monitor endogenous and/or exogenous chemical signals. Some TRP channels monitor osmotic potential, and others measure cell movement, stretching, and fluid flow. Many TRP channels are major players in nociception and integration of pain signals. One member of the vanilloid sub-family of channels is TRPV6. This channel is highly selective for divalent cations, particularly calcium, and plays a part in general whole-body calcium homeostasis, capturing calcium in the gut from the diet. TRPV6 can be greatly elevated in a number of cancers deriving from epithelia and considerable study has been made of its role in the cancer phenotype where calcium control is dysfunctional. This review compiles and updates recent published work on TRPV6 as a promising drug target in a number of cancers including those afflicting breast, ovarian, prostate and pancreatic tissues.
PubMed: 31897233
DOI: 10.7150/jca.31640 -
World Journal of Urology Jun 2021Endourology has undergone fundamental changes over the last 2 decades. Maintaining low intrarenal pressure (IRP) during upper urinary tract procedures is an established... (Review)
Review
PURPOSE
Endourology has undergone fundamental changes over the last 2 decades. Maintaining low intrarenal pressure (IRP) during upper urinary tract procedures is an established concept. However, researchers have not yet studied the concept of reduced intravesical pressures (IVPs) during transurethral (TUR) surgery as thoroughly. Low IVP is supposed to decrease complications as fluid retention, TUR syndrome, and incidence of fever. The study aims to give an overview of the contemporarily existing concepts and specify the term of low IVP to avoid TUR-related complications and optimize TUR-related results.
METHODS
A literature search was performed using PubMed, restricted to original English-written articles, including animal, artificial model, and human studies. Different keywords were transurethral resection, transurethral enucleation, transurethral vaporization, pressure, fluid absorption, and TUR syndrome.
RESULTS
Analyzed mean IVPs during TUR vary between 11 and 35 cmHO but are mostly kept below 30 cmHO. Mean maximum IVPs during TUR range from 20 to 55 cmHO. Maximum IVPs seem to be lower when surgeons utilize continuous flow resection, and irrigation pressures are kept low. The results demonstrate a strong correlation between IVP levels and fluid absorption.
CONCLUSIONS
IVP increase remains a neglected predictor of transurethral procedure complications, and endourologists should consider its intraoperative monitoring. Further research is necessary to quantify generated pressures and introduce means of controlling them.
Topics: Humans; Intraoperative Complications; Pressure; Transurethral Resection of Prostate; Urinary Bladder
PubMed: 32772149
DOI: 10.1007/s00345-020-03401-x -
International Journal of Molecular... Apr 2021Seminal plasma (SP), the non-cellular component of semen, is a heterogeneous composite fluid built by secretions of the testis, the epididymis and the accessory sexual... (Review)
Review
Seminal plasma (SP), the non-cellular component of semen, is a heterogeneous composite fluid built by secretions of the testis, the epididymis and the accessory sexual glands. Its composition, despite species-specific anatomical peculiarities, consistently contains inorganic ions, specific hormones, proteins and peptides, including cytokines and enzymes, cholesterol, DNA and RNA-the latter often protected within epididymis- or prostate-derived extracellular vesicles. It is beyond question that the SP participates in diverse aspects of sperm function pre-fertilization events. The SP also interacts with the various compartments of the tubular genital tract, triggering changes in gene function that prepares for an eventual successful pregnancy; thus, it ultimately modulates fertility. Despite these concepts, it is imperative to remember that SP-free spermatozoa (epididymal or washed ejaculated) are still fertile, so this review shall focus on the differences between the in vivo roles of the SP following semen deposition in the female and those regarding additions of SP on spermatozoa handled for artificial reproduction, including cryopreservation, from artificial insemination to in vitro fertilization. This review attempts, including our own results on model animal species, to critically summarize the current knowledge of the reproductive roles played by SP components, particularly in our own species, which is increasingly affected by infertility. The ultimate goal is to reconcile the delicate balance between the SP molecular concentration and their concerted effects after temporal exposure in vivo. We aim to appraise the functions of the SP components, their relevance as diagnostic biomarkers and their value as eventual additives to refine reproductive strategies, including biotechnologies, in livestock models and humans.
Topics: Animals; Female; Fertility; Humans; Insemination, Artificial; Male; Pregnancy; Reproduction; Semen; Sperm Motility
PubMed: 33922047
DOI: 10.3390/ijms22094368 -
Nature Reviews. Urology Feb 2023Sperm are transcriptionally and translationally quiescent and, therefore, rely on the seminal plasma microenvironment for function, survival and fertilization of the... (Review)
Review
Sperm are transcriptionally and translationally quiescent and, therefore, rely on the seminal plasma microenvironment for function, survival and fertilization of the oocyte in the oviduct. The male reproductive system influences sperm function via the binding and fusion of secreted epididymal (epididymosomes) and prostatic (prostasomes) small extracellular vesicles (S-EVs) that facilitate the transfer of proteins, lipids and nucleic acids to sperm. Seminal plasma S-EVs have important roles in sperm maturation, immune and oxidative stress protection, capacitation, fertilization and endometrial implantation and receptivity. Supplementing asthenozoospermic samples with normospermic-derived S-EVs can improve sperm motility and S-EV microRNAs can be used to predict non-obstructive azoospermia. Thus, S-EV influence on sperm physiology might have both therapeutic and diagnostic potential; however, the isolation of pure populations of S-EVs from bodily fluids with current conventional methods presents a substantial hurdle. Many conventional techniques lack accuracy, effectiveness, and practicality; yet microfluidic technology has the potential to simplify and improve S-EV isolation and detection.
Topics: Humans; Male; Semen; Microfluidics; Sperm Motility; Spermatozoa; Extracellular Vesicles; Infertility, Male
PubMed: 36348030
DOI: 10.1038/s41585-022-00660-8 -
Reproduction in Domestic Animals =... Jan 2022Benign prostatic hyperplasia (BPH) may alter prostatic fluid biochemical composition causing reduced fertility. Osaterone acetate (OA) is an androgen receptor antagonist...
Benign prostatic hyperplasia (BPH) may alter prostatic fluid biochemical composition causing reduced fertility. Osaterone acetate (OA) is an androgen receptor antagonist marketed for treatment of canine BPH. Little information exists on effects of OA administration on biochemical composition of canine prostatic fluid and its role on fertility. The aim of this research was to study biochemical composition of prostatic fluid and its role on semen quality in dogs with BPH undergoing treatment with OA. Eight intact, 5-11-year-old dogs with benign prostatic hyperplasia were treated orally with OA at a dose of 0.25-0.5 mg/kg once daily for seven days. Prostatic volume, semen evaluation and a biochemical analysis of prostatic fluid were performed on the day before treatment (D0), D60, D120, D180 and D240. A significant reduction (57% and 61%) of prostatic volume was observed at D60 and D120, respectively, and a significant reduction (20%) of normal spermatozoa was observed at D60 coincident with a significant increase of sperm tail defects, which disappeared during the course of the treatment. Prostatic fluid composition did not vary during the OA treatment except for zinc (Zn ) with a significant increase at D120 and D180 correlated with the return to normal sperm values. In conclusion, canine Zn prostatic fluid concentrations decrease during development of BPH and return to normal during treatment with OA. Zn is an important electrolyte for semen quality, suggesting that oral Zn supplementation might be considered a treatment to improve semen quality.
Topics: Animals; Chlormadinone Acetate; Dog Diseases; Dogs; Male; Prostatic Hyperplasia; Semen Analysis
PubMed: 34706118
DOI: 10.1111/rda.14030 -
World Journal of Urology Oct 2023Minimal invasiveness improves outcome in many surgical fields including urology. We aimed to assess intraoperative performance and clinical outcome of miniaturized...
BACKGROUND AND PURPOSE
Minimal invasiveness improves outcome in many surgical fields including urology. We aimed to assess intraoperative performance and clinical outcome of miniaturized holmium laser enucleation of prostate (MiLEP) (22FR).
METHODS
We ran a propensity score-matched analysis among all consecutive laser enucleations of prostate performed between 9/2022 and 2/2023. It resulted in two matched comparison groups: MiLEP 22 FR (n = 40) and holmium laser enucleation of prostate (HoLEP 26 Fr) (n = 40). Statistical analysis was performed.
RESULTS
MiLEP was associated with significantly less intraoperative irrigation (20.5 L vs 15 L, p = 0.002), less decrease in body core temperature (0.6°C vs 0.1°C, p = 0.003), and less need for meatal dilation (25% vs 78%, p = 0.01). These parameters were identified as being independent in the multivariate analysis. There was a trend toward less and a shorter period of postoperative stress incontinence (SI) for the MiLEP group compared to the HoLEP group: 15% and 42% (p = 0.01) at 1 month, 8% and 14% (p = 0.07) at 2 months, and 0 and 0.3% (p = 1) at 3 months, respectively. There were no differences in prostatic enucleation effectiveness, operative time, hospital stay, complications, and improvement in the international prostate symptom score and quality of life score.
CONCLUSIONS
MiLEP is feasible and provides better maintenance of body core temperature, reduction in amount of fluid irrigation, and decrease in need for meatal dilation without affecting effectiveness in comparison with HoLEP. MiLEP may reduce early postoperative stress incontinence, thereby shortening the recovery period.
Topics: Male; Humans; Prostatic Hyperplasia; Quality of Life; Propensity Score; Treatment Outcome; Prostate; Transurethral Resection of Prostate; Laser Therapy; Lasers, Solid-State; Postoperative Complications; Holmium
PubMed: 37626182
DOI: 10.1007/s00345-023-04562-1 -
Magnetic Resonance in Medicine May 2024Prostate tissue has a complex microstructure, mainly composed of epithelial and stromal cells, and of extracellular (acinar-luminal) spaces. Diffusion-weighted MR...
PURPOSE
Prostate tissue has a complex microstructure, mainly composed of epithelial and stromal cells, and of extracellular (acinar-luminal) spaces. Diffusion-weighted MR spectroscopy (DW-MRS) is ideally suited to explore complex microstructure in vivo with metabolites selectively distributed in different subspaces. To date, this technique has been applied to brain and muscle. This study presents the development and pioneering utilization of H-DW-MRS in the prostate, accompanied by in vitro studies to support interpretations of in vivo findings.
METHODS
Nine healthy volunteers underwent a prostate MR examination (mean age, 56 years; range, 31-66). Metabolic complexation was studied in vitro using solutions with major compounds found in prostatic fluid of the lumen. DW-MRS was performed at 3 T with a non-water-suppressed single-voxel sequence with metabolite-cycling to concurrently measure metabolite and water signals. The water signal was used in postprocessing as a reference in a motion-compensation scheme. The spectra were fitted simultaneously in the spectral and diffusion-weighting dimensions. Apparent diffusion coefficients (ADCs) were derived by fitting signal decays that were assumed to be mono-exponential for metabolites and biexponential for water.
RESULTS
DW-MRS of the prostate revealed relatively low ADCs for Cho and Cr compounds, aligning with their intracellular location and higher ADCs for citrate and spermine supporting their luminal origin. In vitro assessments of the ADCs of citrate and spermine demonstrated their complex formation and protein binding. Tissue concentrations of MRS-detectable metabolites were as expected for the voxel location.
CONCLUSIONS
This work successfully demonstrates the feasibility of H-DW-MRS of the prostate and its potential for providing valuable microstructural information.
PubMed: 38775024
DOI: 10.1002/mrm.30141 -
APMIS : Acta Pathologica,... Apr 2022Cutibacterium acnes has been associated with chronic prostatitis, which can potentially favor the appearance of tumors in the prostate. Prostatitis is difficult to...
Cutibacterium acnes has been associated with chronic prostatitis, which can potentially favor the appearance of tumors in the prostate. Prostatitis is difficult to treat, and the drug needs to be able to penetrate the prostate. The aim was to investigate the pharmacokinetics of clindamycin in the interstitial fluid of rat prostate using microdialysis. Microdialysis probes were recovered in vitro and in vivo. Clindamycin was administered at 80 mg/kg iv bolus for plasma and tissue pharmacokinetic experiments. A microdialysis probe was implanted in the prostate gland for collections over an 8-hour period. The pharmacokinetic parameters were determined by both compartmental and non-compartmental approaches. Penetration was determined as the ratio between the area under the curve and the time of the clindamycin measurement in the prostate. The recovery of the in vivo probes was 38.11 ± 1.14%. The plasma profile was modeled by a two-compartment pharmacokinetic model. Clindamycin presented a prostate/plasma ratio of 1.02, with free concentrations above the minimum inhibitory concentration for Cutibacterium acnes isolates. This was the first study that determined clindamycin free concentrations in the prostatic fluid of rats. These findings suggest that clindamycin may be an effective alternative for the treatment of prostatitis caused by Cutibacterium acnes.
Topics: Animals; Anti-Bacterial Agents; Clindamycin; Male; Microbial Sensitivity Tests; Prostate; Prostatitis; Rats
PubMed: 34978745
DOI: 10.1111/apm.13205