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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 -
Developmental Biology Jan 2003The prostate is a male accessory sex gland found only in mammals that functions to produce a major fraction of seminal fluid. Interest in understanding the biology of... (Review)
Review
The prostate is a male accessory sex gland found only in mammals that functions to produce a major fraction of seminal fluid. Interest in understanding the biology of the prostate is driven both by the fascinating nature of the developmental processes that give rise to the prostate and by the high incidence in humans of prostatic diseases, including prostatic adenocarcinoma and benign prostatic hyperplasia. This review summarizes the current state of knowledge of the cellular and molecular processes that control prostatic development. Insight into the mechanisms that control prostatic development has come from experimental embryological work as well as from the study of mice and humans harboring mutations that alter prostatic development. These studies have demonstrated a requirement for androgens throughout prostatic development and have revealed a series of reciprocal paracrine signals between the developing prostatic epithelium and prostatic mesenchyme. Finally, these studies have identified several specific gene products that are required for prostatic development. While research in recent years has greatly enhanced our understanding of the molecular control of prostatic development, known genes cannot yet explain in molecular terms the complex biological interactions that descriptive and experimental embryological studies have elucidated in the control of prostatic development.
Topics: Androgens; Animals; Gene Expression Regulation, Developmental; Humans; Male; Mice; Mice, Knockout; Morphogenesis; Mutation; Prostate; Steroids
PubMed: 12645922
DOI: 10.1016/s0012-1606(02)00031-3 -
Prostate Cancer and Prostatic Diseases 2009Early detection is the key to effective treatment of prostate cancer, and to the prevention of deaths due to progression to untreatable advanced stage cancer. Because of... (Review)
Review
Early detection is the key to effective treatment of prostate cancer, and to the prevention of deaths due to progression to untreatable advanced stage cancer. Because of mitigating factors, especially benign prostatic hyperplasia (BPH), that result in a low accuracy (about 60%) of prostate-specific antigen (PSA) testing, there is an urgent need for a more reliable biomarker for the identification of early stage through advanced stage prostate cancer and 'at-risk' individuals. To address this issue we propose that changes in prostatic fluid composition could provide accurate and reliable biomarkers for the screening of prostate cancer. Most notable is the consistent and significant decrease in citrate and zinc that is associated with the development and progression of prostate cancer. In this review we provide the clinical and physiological basis and the evidence in support of the utility of prostatic fluid analysis as an effective approach for screening/detection of prostate cancer, especially early stage and 'at-risk' subjects. The problem of BPH interference that plagues PSA testing is eliminated in the potential prostatic fluid biomarkers. The potential development of rapid, simple, direct, accurate clinical tests provides additional advantageous conditions. Further exploration and development of citrate, zinc and other electrolytes as prostatic fluid biomarkers are urgently needed to address this critical prostate cancer issue.
Topics: Biomarkers, Tumor; Body Fluids; Citric Acid; Early Detection of Cancer; Electrolytes; Humans; Male; Mass Screening; Prostatic Neoplasms; Zinc
PubMed: 18591961
DOI: 10.1038/pcan.2008.19 -
Proteomic discovery of non-invasive biomarkers of localized prostate cancer using mass spectrometry.Nature Reviews. Urology Dec 2021Prostate cancer is the second most frequently diagnosed non-skin cancer in men worldwide. Patient outcomes are remarkably heterogeneous and the best existing clinical... (Review)
Review
Prostate cancer is the second most frequently diagnosed non-skin cancer in men worldwide. Patient outcomes are remarkably heterogeneous and the best existing clinical prognostic tools such as International Society of Urological Pathology Grade Group, pretreatment serum PSA concentration and T-category, do not accurately predict disease outcome for individual patients. Thus, patients newly diagnosed with prostate cancer are often overtreated or undertreated, reducing quality of life and increasing disease-specific mortality. Biomarkers that can improve the risk stratification of these patients are, therefore, urgently needed. The ideal biomarker in this setting will be non-invasive and affordable, enabling longitudinal evaluation of disease status. Prostatic secretions, urine and blood can be sources of biomarker discovery, validation and clinical implementation, and mass spectrometry can be used to detect and quantify proteins in these fluids. Protein biomarkers currently in use for diagnosis, prognosis and relapse-monitoring of localized prostate cancer in fluids remain centred around PSA and its variants, and opportunities exist for clinically validating novel and complimentary candidate protein biomarkers and deploying them into the clinic.
Topics: Biomarkers, Tumor; Early Detection of Cancer; Humans; Male; Mass Spectrometry; Prognosis; Prostatic Neoplasms; Proteomics; Risk Assessment
PubMed: 34453155
DOI: 10.1038/s41585-021-00500-1 -
Current Cancer Drug Targets 2018Prostate cancer (PCa) is the most common non-skin cancer in men worldwide, resulting in significant mortality and morbidity. Depending on the grade and stage of the... (Review)
Review
Prostate cancer (PCa) is the most common non-skin cancer in men worldwide, resulting in significant mortality and morbidity. Depending on the grade and stage of the cancer, patients may be given radiation therapy, hormonal therapy, or chemotherapy. However, more than half of these patients develop resistance to treatment, leading to disease progression and metastases, often with lethal consequences. MicroRNAs (miRNAs) are short, non-coding RNAs, which regulate numerous physiological as well as pathological processes, including cancer. miRNAs mediate their regulatory effect predominately by binding to the 3'-untranslated region (UTR) of their target mRNAs. In this review, we will describe the mechanisms by which miRNAs mediate resistance to radiation and drug therapy (i.e. hormone therapy and chemotherapy) in PCa, including control of apoptosis, cell growth and proliferation, autophagy, epithelial-to-mesenchymal transition (EMT), invasion and metastasis, and cancer stem cells (CSCs). Furthermore, we will discuss the utility of circulating miRNAs isolated from different body fluids of prostate cancer patients as non-invasive biomarkers of cancer detection, disease progression, and therapy response. Finally, we will shortlist the candidate miRNAs, which may have a role in drug and radioresistance, that could potentially be used as predictive biomarkers of treatment response.
Topics: Animals; Apoptosis; Biomarkers, Tumor; Body Fluids; Disease Progression; Drug Resistance, Neoplasm; Humans; Male; Mice; MicroRNAs; Prostatic Neoplasms, Castration-Resistant
PubMed: 29644941
DOI: 10.2174/1568009618666180315160125 -
Archivos Espanoles de Urologia Sep 2018Prostate cancer is the most frequent neoplasia diagnosed in males. Treatment of metastatic prostate cancer is based on androgen deprivation therapy (ADT) up to its... (Review)
Review
OBJECTIVES
Prostate cancer is the most frequent neoplasia diagnosed in males. Treatment of metastatic prostate cancer is based on androgen deprivation therapy (ADT) up to its change to the castration resistance state. Recently, new molecules have been developed that significantly increase survival and quality of life of these patients. Abiraterone acetate in combination with prednisone is the first oral hormone therapy that contributed to this change in the approach of the disease.
METHODS
Systematic bibliographic review about abiraterone in the treatment of metastatic castration resistant prostate cancer (CPRC), with data on efficacy, safety and quality of life.
RESULTS
Treatment with abiraterone and prednisone has demonstrated a significant increase in overall survival (OS 34.7 vs 30.3 months) and radiologic progression free survival (RPFS 16.5 months vs 8.3 months) in comparison to placebo and prednisone in patients with metastatic castration resistant prostate cancer (mCPRC). It also demonstrated an increase in OS and RPFS compared to placebo plus prednisone in mCPRC patients after at least one cytotoxic chemotherapy based treatment (OS 15.8 vs 11.2 months; RPFS 5.6 vs 3.6 months). Side effects related to abiraterone therapy are mainly related with mineral corticoid excess (Hypertension, hypokalemia, fluid retention) and, to a lesser extent, transaminase alterations or cardiovascular effects. Perceived quality of life results show a benefit in the abiraterone treatment group.
CONCLUSIONS
Abiraterone acetate is a new hormonal treatment for metastatic castration resistant prostate cancer both before and after chemotherapy. The results of the available studies demonstrate a significant improvement in terms of efficacy, with a tolerability profile generally acceptable, predictable and manageable, and an improvement in patient's perceived quality of life.
Topics: Androstenes; Humans; Male; Prostatic Neoplasms, Castration-Resistant
PubMed: 30319125
DOI: No ID Found -
American Journal of Translational... 2021To study the effect of Qianliekang tablets on the clinical efficacy, immune function, and inflammatory factor levels in the prostatic fluid of elderly chronic...
The effect of Qianliekang tablets on the clinical efficacy, immune function, and inflammatory factor levels in the prostatic fluid of elderly chronic prostatitis patients.
PURPOSE
To study the effect of Qianliekang tablets on the clinical efficacy, immune function, and inflammatory factor levels in the prostatic fluid of elderly chronic prostatitis (CP) patients.
METHODS
106 elderly CP patients admitted to our hospital between June 2018 and June 2020 were recruited as the study cohort and randomly divided into a regular group and an observation group. The regular group was administered tamsulosin hydrochloride, and the observation group was administered a combination of tamsulosin hydrochloride and Qianliekang tablets. After a course of treatment, the clinical efficacy, the changes in the patients' symptoms, the function scores, the prostate ultrasound indicators, the changes in the T lymphocyte subsets, and the inflammatory factor expression levels in the prostatic fluid before and after the treatment were measured and compared in the two groups. The occurrence of adverse effects during the treatment was statistically analyzed.
RESULTS
The overall effectiveness rate in the observation group was superior to the overall effectiveness rate in the regular group (94.34% vs. 75.47%, P < 0.05). There were no significant differences in the patient clinical data before the treatment in the two groups (P > 0.05). After the treatment, the CD /CD immune function indicators, the prostatic fluid inflammatory factor levels, the symptom function scores, and the prostate ultrasound indicators in the observation group were better than they were in the regular group (all P < 0.05). No significant differences were found in the incidence of adverse effects between the two groups (P > 0.05).
CONCLUSION
Qianliekang tablets can improve the curative effect in elderly CP patients, enhance their immune function, and reduce the inflammatory factor expression levels in their prostatic fluid.
PubMed: 34306506
DOI: No ID Found -
Journal of Smooth Muscle Research =... 2017The prostate is a gland whose secretions contribute to the seminal fluids ejaculated upon activation of autonomic sympathetic nerves. In elder males, the prostate... (Review)
Review
The prostate is a gland whose secretions contribute to the seminal fluids ejaculated upon activation of autonomic sympathetic nerves. In elder males, the prostate undergoes an increase in stroma mass and myogenic tone, leading to benign prostatic hyperplasia that occludes the proximal urethra and the presentation of various lower urinary tract symptoms that decrease their quality of life. This review summarises the role of prostatic interstitial cells (PICs) in the generation of the spontaneous tone in the prostate. It presents current knowledge of the role of Ca plays in PIC pacemaking, as well as the mechanisms by which this spontaneous activity triggers slow wave generation and stromal contraction. PICs display a small T-type Ca current (I) and a large L-type Ca current (I). In contrast to other interstitial cells in the urinary and gastrointestinal tracts, spontaneous Ca signalling in PICs is uniquely dependent on Ca influx through I channels. A model of prostatic pacemaking is presented describing how I can be triggered by an initial membrane depolarization evoked upon the selective opening of Ca-activated Cl channels by Ca flowing only through I channels. The resulting current flow through I results in release of Ca from internal stores and the summation of Cl-selective spontaneous transient depolarizations (STDs) to form pacemaker potentials that propagate passively into the prostatic stroma to evoke regenerative action potentials and excitation-contraction coupling.
Topics: Action Potentials; Animals; Biological Clocks; Calcium; Calcium Channels; Calcium Signaling; Chloride Channels; Electrophysiological Phenomena; Gerbillinae; Guinea Pigs; Humans; In Vitro Techniques; Ion Channels; Male; Mice; Prostate; Prostatic Hyperplasia; Rats; Sympathetic Nervous System; Synaptic Transmission
PubMed: 28652517
DOI: 10.1540/jsmr.53.57 -
Medicina 2022Bleeding is the most common complication after a prostate biopsy, commonly self-limited. We describe a case of a patient who developed a hemoperitoneum after a...
Bleeding is the most common complication after a prostate biopsy, commonly self-limited. We describe a case of a patient who developed a hemoperitoneum after a transperineal prostate biopsy. A 65-year-old man with a history of prostate cancer diagnosed in 2016 by transurethral resection, with no further urologic control until 2020 when a rise in the serum prostate-specific antigen was diagnosed: 4.49 ng/ml. Prostate digital rectal examination had no pathologic findings. Magnetic resonance imaging informed anequivocal lesion. A target transperineal fusion biopsy was performed, guided by ultrasound (US). Pre-surgical blood tests, including coagulogram, were normal. No immediate postoperative complications were recorded, and the patient was discharged. Hours later, he returned after a head concussion due to orthostatic hypotension and diffuse abdominal pain. Blood test showed a drop in hematocrit and hemoglobin values. Abdominal US and abdominopelvic computed tomography scan showed free intraperitoneal fluid and intraperitoneal hematic collection on top of the bladder of 104 × 86 mm with no active bleeding. The patient was admitted to intensive care unit due to persistent hypotension despite fluid restoration. He received a single-unit blood transfusion and had a good response to vasopressors. Abdominal pain decreased. He was finally discharged with stable hematocrit 48hours after admission. Clinical management with no surgery or radiologic angio-embolization was required. We found no clear origin of the intraperitoneal bleeding, but we hypothesize that maybe the previous transurethral resection of the prostate made anatomical changes that facilitated blood passage to the abdominal cavity after puncture of branches from the inferior vesical artery.
Topics: Abdominal Pain; Aged; Hemoperitoneum; Humans; Image-Guided Biopsy; Male; Prostate; Transurethral Resection of Prostate; Ultrasonography, Interventional
PubMed: 35639070
DOI: No ID Found -
International Journal of Molecular... Sep 2014Prostate cancer (PC) is the most commonly diagnosed neoplasm and the third most common cause of cancer-related death amongst men in the Western world. PC is a clinically... (Review)
Review
Prostate cancer (PC) is the most commonly diagnosed neoplasm and the third most common cause of cancer-related death amongst men in the Western world. PC is a clinically highly heterogeneous disease, and distinction between aggressive and indolent disease is a major challenge for the management of PC. Currently, no biomarkers or prognostic tools are able to accurately predict tumor progression at the time of diagnosis. Thus, improved biomarkers for PC prognosis are urgently needed. This review focuses on the prognostic potential of DNA methylation biomarkers for PC. Epigenetic changes are hallmarks of PC and associated with malignant initiation as well as tumor progression. Moreover, DNA methylation is the most frequently studied epigenetic alteration in PC, and the prognostic potential of DNA methylation markers for PC has been demonstrated in multiple studies. The most promising methylation marker candidates identified so far include PITX2, C1orf114 (CCDC181) and the GABRE~miR-452~miR-224 locus, in addition to the three-gene signature AOX1/C1orf114/HAPLN3. Several other biomarker candidates have also been investigated, but with less stringent clinical validation and/or conflicting evidence regarding their possible prognostic value available at this time. Here, we review the current evidence for the prognostic potential of DNA methylation markers in PC.
Topics: Adenocarcinoma; Biomarkers; Body Fluids; DNA Methylation; DNA, Neoplasm; Early Detection of Cancer; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Male; MicroRNAs; Microtubule Proteins; Neoplasm Invasiveness; Neoplasm Proteins; Predictive Value of Tests; Prognosis; Promoter Regions, Genetic; Prostatic Neoplasms; Proteins; RNA, Neoplasm
PubMed: 25238417
DOI: 10.3390/ijms150916544