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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 -
Translational Andrology and Urology Aug 2016Men with post orgasmic illness syndrome (POIS) become ill rather immediately after ejaculation, whether spontaneously at night, during sexual intercourse or... (Review)
Review
Men with post orgasmic illness syndrome (POIS) become ill rather immediately after ejaculation, whether spontaneously at night, during sexual intercourse or masturbation. Two subtypes are distinguished: primary and secondary POIS. It also occurs before or after a man has been sterilized. POIS is an invalidating most probably auto-immune disease leading to much distress in males and their partners. It is characterized by five criteria. Its symptoms are described by seven clusters. However, the manifestation of these symptoms varies from one male to the other but is relatively constant in the person himself. Among men the symptoms vary in intensity, durations and sort of symptoms. POIS is a chronic disorder that manifests itself in POIS "attacks" that occur within a few minutes to a few hours after ejaculation, and disappear spontaneously after 3 to 7 days. POIS is not associated with increased total serum IgE concentrations. On the contrary, there are indications that POIS is triggered by specific cytokines that are released by an auto-immune reaction to the man's seminal fluid. Indirect clinical evidence suggests that the antigen (Ag) triggering the POIS systemic reaction is not bound to spermatozoa but to seminal fluid produced by prostatic tissue. In addition, POIS may also occur-although rarely-in females. In those cases, it is hypothesized that the Ag is associated with female prostatic tissue around the vagina.
PubMed: 27652231
DOI: 10.21037/tau.2016.07.01 -
World Journal of Surgical Oncology Feb 2019The giant multilocular prostatic cystadenoma is a very rare benign tumor of the prostate gland. It is composed of predominantly cystic enlarged prostatic glands in a...
BACKGROUND
The giant multilocular prostatic cystadenoma is a very rare benign tumor of the prostate gland. It is composed of predominantly cystic enlarged prostatic glands in a fibrous stroma and spreads extensively into the pelvis. Because of the large size at the time of diagnosis, it is not always possible to determine the exact point of origin for these multilocular cystic neoplasms. Thus, diagnosis before histological examination of a surgical specimen is often difficult. Here, we present a case involving one of the largest giant multilocular prostatic cystadenomas reported in the literature and discuss preoperative diagnoses and appropriate surgical approaches for this rare retroperitoneal tumor.
CASE PRESENTATION
A 50-year-old man presented with a 2-year history of abdominal distension and lower urinary symptoms. Enhanced CT showed a large retroperitoneal mass with multiple septations in the pelvis and lower abdomen, measuring 30 cm in size, surrounding the rectum and displacing the bladder, prostate, and seminal vesicle to the right anterior side. MRI showed multiple cysts with a simple fluid appearance on T2-weighted images and enhanced solid components on gadolinium-enhanced fat-saturated T1-weighted images, suggesting the retroperitoneal mass as leiomyoma with cystic degeneration or perivascular epithelioid cell tumor. Biopsy of the mass showed a spindle cell tumor with focal smooth muscle differentiation. Differential diagnosis comprising leiomyoma, low-grade leiomyosarcoma, and perivascular epithelioid cell tumor was made. Complete resection of the tumor with low anterior resection of the rectum was performed. The tumor was solid with multilocular cavities containing blackish-brown fluid and measured 33 × 23 × 10 cm. Histologically, the tumor was composed of variously sized dilated glandular structures lined by prostatic epithelia surrounded by fibromuscular stroma. The prostatic nature of the lesions was confirmed by immunohistochemical staining of the epithelium for prostate-specific antigen. Thus, pathological diagnosis was a giant multilocular prostatic cystadenoma.
CONCLUSIONS
We present our experiences with one of the largest giant multilocular prostatic cystadenomas. When a retroperitoneal huge lesion with locular cavities fills the pelvis in a male patient, the possibility of giant multilocular prostatic cystadenoma should be considered before planning for retroperitoneal tumor treatment.
Topics: Biopsy; Cystadenoma; Diagnosis, Differential; Humans; Leiomyoma; Leiomyosarcoma; Magnetic Resonance Imaging; Male; Middle Aged; Perivascular Epithelioid Cell Neoplasms; Prostate; Prostatectomy; Prostatic Neoplasms; Retroperitoneal Space; Tomography, X-Ray Computed; Treatment Outcome; Tumor Burden
PubMed: 30808350
DOI: 10.1186/s12957-019-1579-7 -
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 -
International Journal of Clinical... Nov 2017To raise awareness on nocturia disease burden and to provide simplified aetiologic evaluation and related treatment pathways. (Review)
Review
AIM
To raise awareness on nocturia disease burden and to provide simplified aetiologic evaluation and related treatment pathways.
METHODS
A multidisciplinary group of nocturia experts developed practical advice and recommendations based on the best available evidence supplemented by their own experiences.
RESULTS
Nocturia is defined as the need to void ≥1 time during the sleeping period of the night. Clinically relevant nocturia (≥2 voids per night) affects 2%-18% of those aged 20-40 years, rising to 28%-62% for those aged 70-80 years. Consequences include the following: lowered quality of life; falls and fractures; reduced work productivity; depression; and increased mortality. Nocturia-related hip fractures alone cost approximately €1 billion in the EU and $1.5 billion in the USA in 2014. The pathophysiology of nocturia is multifactorial and typically related to polyuria (either global or nocturnal), reduced bladder capacity or increased fluid intake. Accurate assessment is predicated on frequency-volume charts combined with a detailed patient history, medicine review and physical examination. Optimal treatment should focus on the underlying cause(s), with lifestyle modifications (eg, reducing evening fluid intake) being the first intervention. For patients with sustained bother, medical therapies should be introduced; low-dose, gender-specific desmopressin has proven effective in nocturia due to idiopathic nocturnal polyuria. The timing of diuretics is an important consideration, and they should be taken mid-late afternoon, dependent on the specific serum half-life. Patients not responding to these basic treatments should be referred for specialist management.
CONCLUSIONS
The cause(s) of nocturia should be first evaluated in all patients. Afterwards, the underlying pathophysiology should be treated specifically, alone with lifestyle interventions or in combination with drugs or (prostate) surgery.
Topics: Antidiuretic Agents; Deamino Arginine Vasopressin; Humans; Life Style; Nocturia; Polyuria; Quality of Life
PubMed: 28984060
DOI: 10.1111/ijcp.13027 -
International Journal of Molecular... Sep 2023Extracellular vesicles (EVs)-including apoptotic bodies, microvesicles, and exosomes-are released by almost all cell types and contain molecular footprints from their... (Review)
Review
Extracellular vesicles (EVs)-including apoptotic bodies, microvesicles, and exosomes-are released by almost all cell types and contain molecular footprints from their cell of origin, including lipids, proteins, metabolites, RNA, and DNA. They have been successfully isolated from blood, urine, semen, and other body fluids. In this review, we discuss the current understanding of the predictive value of EVs in prostate and renal cancer. We also describe the findings supporting the use of EVs from liquid biopsies in stratifying high-risk prostate/kidney cancer and advanced disease, such as castration-resistant (CRPC) and neuroendocrine prostate cancer (NEPC) as well as metastatic renal cell carcinoma (RCC). Assays based on EVs isolated from urine and blood have the potential to serve as highly sensitive diagnostic studies as well as predictive measures of tumor recurrence in patients with prostate and renal cancers. Overall, we discuss the biogenesis, isolation, liquid-biopsy, and therapeutic applications of EVs in CRPC, NEPC, and RCC.
Topics: Male; Humans; Carcinoma, Renal Cell; Prostate; Prostatic Neoplasms, Castration-Resistant; Clinical Relevance; Kidney Neoplasms; Neoplasm Recurrence, Local; Extracellular Vesicles; Exosomes
PubMed: 37834162
DOI: 10.3390/ijms241914713 -
The Journal of Clinical Investigation Apr 2016New biomarkers are needed to improve the diagnosis of prostate cancer. Similarly to healthy cells, prostate epithelial cancer cells produce extracellular vesicles... (Review)
Review
New biomarkers are needed to improve the diagnosis of prostate cancer. Similarly to healthy cells, prostate epithelial cancer cells produce extracellular vesicles (prostasomes) that can be isolated from seminal fluid, urine, and blood. Prostasomes contain ubiquitously expressed and prostate-specific membrane and cytosolic proteins, as well as RNA. Both quantitative and qualitative changes in protein, mRNA, long noncoding RNA, and microRNA composition of extracellular vesicles isolated from prostate cancer patients have been reported. In general, however, the identified extracellular vesicle-associated single-marker molecules or combinations of marker molecules require confirmation in large cohorts of patients to validate their specificity and sensitivity as prostate cancer markers. Complications include variable factors such as prostate manipulation and urine flux, as well as masking by ubiquitously expressed free molecules and extracellular vesicles from tissues other than the prostate. Herein, we propose that the most promising methods include comprehensive combinational screening for (mutant) RNA in prostasomes that are immunoisolated with antibodies targeting prostate-specific epitopes.
Topics: Animals; Biomarkers, Tumor; Humans; Male; MicroRNAs; Neoplasm Proteins; Prostatic Neoplasms; Proteasome Endopeptidase Complex; RNA, Long Noncoding; RNA, Messenger; RNA, Neoplasm
PubMed: 27035806
DOI: 10.1172/JCI81128