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Cell Reports Dec 2021The prostate gland produces prostatic fluid, high in zinc and citrate and essential for the maintenance of spermatozoa. Prostate cancer is a common condition with...
The prostate gland produces prostatic fluid, high in zinc and citrate and essential for the maintenance of spermatozoa. Prostate cancer is a common condition with limited treatment efficacy in castration-resistant metastatic disease, including with immune checkpoint inhibitors. Using single-cell RNA-sequencing to perform an unbiased assessment of the cellular landscape of human prostate, we identify a subset of tumor-enriched androgen receptor-negative luminal epithelial cells with increased expression of cancer-associated genes. We also find a variety of innate and adaptive immune cells in normal prostate that were transcriptionally perturbed in prostate cancer. An exception is a prostate-specific, zinc transporter-expressing macrophage population (MAC-MT) that contributes to tissue zinc accumulation in homeostasis but shows enhanced inflammatory gene expression in tumors, including T cell-recruiting chemokines. Remarkably, enrichment of the MAC-MT signature in cancer biopsies is associated with improved disease-free survival, suggesting beneficial antitumor functions.
Topics: Aged; Animals; Epithelial Cells; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Macrophages; Male; Mice; Mice, Inbred C57BL; Middle Aged; Prostate; Prostatic Neoplasms; RNA-Seq; Receptors, Androgen; Single-Cell Analysis; Transcriptome; Zinc
PubMed: 34936871
DOI: 10.1016/j.celrep.2021.110132 -
International Journal of Molecular... Jan 2022The role of endocrine disruptors (EDs) in the human prostate gland is an overlooked issue even though the prostate is essential for male fertility. From experimental... (Review)
Review
The role of endocrine disruptors (EDs) in the human prostate gland is an overlooked issue even though the prostate is essential for male fertility. From experimental models, it is known that EDs can influence several molecular mechanisms involved in prostate homeostasis and diseases, including prostate cancer (PCa), one of the most common cancers in the male, whose onset and progression is characterized by the deregulation of several cellular pathways including androgen receptor (AR) signaling. The prostate gland essentiality relies on its function to produce and secrete the prostatic fluid, a component of the seminal fluid, needed to keep alive and functional sperms upon ejaculation. In physiological condition, in the prostate epithelium the more-active androgen, the 5α-dihydrotestosterone (DHT), formed from testosterone (T) by the 5α-reductase enzyme (SRD5A), binds to AR and, upon homodimerization and nuclear translocation, recognizes the promoter of target genes modulating them. In pathological conditions, AR mutations and/or less specific AR binding by ligands modulate differently targeted genes leading to an altered regulation of cell proliferation and triggering PCa onset and development. EDs acting on the AR-dependent signaling within the prostate gland can contribute to the PCa onset and to exacerbating its development.
Topics: Animals; Endocrine Disruptors; Gene Expression Regulation, Neoplastic; Humans; Male; Prostatic Neoplasms; Receptors, Androgen
PubMed: 35163140
DOI: 10.3390/ijms23031216 -
Cancer Metastasis Reviews Jun 2020Caveolae are specialised and dynamic plasma membrane subdomains, involved in many cellular functions including endocytosis, signal transduction, mechanosensing and lipid... (Review)
Review
Caveolae are specialised and dynamic plasma membrane subdomains, involved in many cellular functions including endocytosis, signal transduction, mechanosensing and lipid storage, trafficking, and metabolism. Two protein families are indispensable for caveola formation and function, namely caveolins and cavins. Mutations of genes encoding these caveolar proteins cause serious pathological conditions such as cardiomyopathies, skeletal muscle diseases, and lipodystrophies. Deregulation of caveola-forming protein expression is associated with many types of cancers including prostate cancer. The distinct function of secretion of the prostatic fluid, and the unique metabolic phenotype of prostate cells relying on lipid metabolism as a main bioenergetic pathway further suggest a significant role of caveolae and caveolar proteins in prostate malignancy. Accumulating in vitro, in vivo, and clinical evidence showed the association of caveolin-1 with prostate cancer grade, stage, metastasis, and drug resistance. In contrast, cavin-1 was found to exhibit tumour suppressive roles. Studies on prostate cancer were the first to show the distinct function of the caveolar proteins depending on their localisation within the caveolar compartment or as cytoplasmic or secreted proteins. In this review, we summarise the roles of caveola-forming proteins in prostate cancer and the potential of exploiting them as therapeutic targets or biological markers.
Topics: Animals; Caveolae; Caveolins; Humans; Male; Membrane Proteins; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant; RNA-Binding Proteins
PubMed: 32358634
DOI: 10.1007/s10555-020-09874-x -
American Family Physician Jun 2023Lower urinary tract symptoms from benign prostatic hyperplasia affect 25% of U.S. men, nearly one-half of whom have at least moderate symptoms. Sedentary lifestyle,...
Lower urinary tract symptoms from benign prostatic hyperplasia affect 25% of U.S. men, nearly one-half of whom have at least moderate symptoms. Sedentary lifestyle, hypertension, and diabetes mellitus increase risk of symptoms. Evaluation is focused on determining severity of symptoms and therapy to improve symptoms. Rectal examination has limited accuracy in evaluating prostate size. Transrectal ultrasonography is preferred to verify size when starting 5-alpha reductase therapy or considering surgery. Serum prostate-specific antigen testing is not recommended in routine evaluation of lower urinary tract symptoms, and shared decision-making should be used for cancer screening decisions. The International Prostate Symptom Score is the best way to track symptoms. Self-management methods, including limiting evening fluid intake, reducing caffeine and alcohol intake, toilet and bladder training, pelvic floor exercises, and mindfulness techniques, can improve symptoms. Although saw palmetto is not effective, the herbal treatments Pygeum africanum and beta-sitosterol may be effective. Primary medical treatment involves alpha blockers or phosphodiesterase-5 inhibitors. Alpha blockers offer rapid benefit and can be used for acute urinary retention. Combining alpha blockers and phosphodiesterase-5 inhibitors is not beneficial. For uncontrolled symptoms, 5-alpha reductase inhibitors should be started if the prostate volume is 30 mL or greater by ultrasonography. 5-Alpha reductase inhibitors take up to one year to be fully beneficial and are more effective when taken with alpha blockers. Only 1% of patients with lower urinary tract symptoms require surgery. Although transurethral resection of the prostate improves symptoms, many less invasive options with varying effectiveness can be considered.
Topics: Male; Humans; Transurethral Resection of Prostate; Prostatic Hyperplasia; 5-alpha Reductase Inhibitors; Cyclic Nucleotide Phosphodiesterases, Type 5; Adrenergic alpha-Antagonists; Lower Urinary Tract Symptoms
PubMed: 37327163
DOI: No ID Found -
Critical Reviews in Oncology/hematology Sep 2019The human microbiome is an emerging target in cancer development and therapeutics. It may be directly oncogenic, through promotion of mucosal inflammation or systemic... (Review)
Review
The human microbiome is an emerging target in cancer development and therapeutics. It may be directly oncogenic, through promotion of mucosal inflammation or systemic dysregulation, or may alter anti-cancer immunity/therapy. Microorganisms within, adjacent to and distant from tumors may affect cancer progression, and interactions and differences between these populations can influence the course of disease. Here we review the microbiome as it pertains to cancer for clinicians. The microbiota of cancers including colorectal, pancreas, breast and prostate are discussed. We examine "omics" technologies, microbiota associated with tumor tissue and tumor-site fluids such as feces and urine, as well as indirect effects of the gut microbiome. We describe roles of the microbiome in immunotherapy, and how it can be modulated to improve cancer therapeutics. While research is still at an early stage, there is potential to exploit the microbiome, as modulation may increase efficacy of treatments, reduce toxicities and prevent carcinogenesis.
Topics: Carcinogenesis; Female; Gastrointestinal Microbiome; Humans; Immunity; Immunologic Factors; Immunotherapy; Male; Microbiota; Neoplasms
PubMed: 31202124
DOI: 10.1016/j.critrevonc.2019.06.004 -
Biomedicine & Pharmacotherapy =... Apr 2022Exosomes are nano-sized structures that are found in semen, epididymal -fluid, endometrium, as well as in follicular fluid. They are responsible for transporting... (Review)
Review
Exosomes are nano-sized structures that are found in semen, epididymal -fluid, endometrium, as well as in follicular fluid. They are responsible for transporting bioactive cargo- proteins, lipids, and nucleic acids. Exosomes have been proven to influence processes in both female and male reproductive systems, including gametogenesis, acrosomal reaction, sperm capacitation, and embryo implantation in the endometrium. Exosomes are made of the same particles as the cells they come from and are secreted by normal and pathological cells. Therefore, exosomes can reflect the physiological state of cells. Moreover, due to the transportation of biomolecules, they participate in intercellular communication and can be used as biomarkers of many diseases, including ovarian, endometrial and prostate cancer. Identification of exosomes as biomarkers could contribute to a better understanding of genital dysfunction and fertility disorders.
Topics: Aging; Biomarkers; Drug Carriers; Embryo Implantation; Exosomes; Female; Genital Diseases, Female; Genital Diseases, Male; Genitalia, Female; Genitalia, Male; Humans; Inflammation; Male; Reproduction; Signal Transduction
PubMed: 35220028
DOI: 10.1016/j.biopha.2022.112752 -
Journal of Gynecology Obstetrics and... Mar 2021Current scientific evidence reveals the importance of the human microbiome in health and disease. The presence of microbiota within the male and female reproductive... (Review)
Review
Current scientific evidence reveals the importance of the human microbiome in health and disease. The presence of microbiota within the male and female reproductive tract has been well-documented and present theories imply that a possible disruption of their concentrations may have adverse effects on reproductive health and reproductive outcomes. Altered endometrial and vaginal microbiome could potential affect the reproductive outcome in infertile couples undergoing assisted reproductive techniques. Analysis of seminal fluids could also facilitate a prompt and appropriate approach in cases of abnormal male reproductive microflora. Essential knowledge on this subject could provide fertility experts better understanding with regards to unexplained fertility, increasing the success rates of ARTs. In this review, we summarise the current knowledge on the microbiota of the male and female reproductive tract and its impact on the success rates of ARTs in infertile couples.
Topics: Bacteria; Endometrium; Fallopian Tubes; Female; Genitalia; Humans; Infertility; Male; Microbiota; Ovary; Pregnancy; Pregnancy Outcome; Reproductive Techniques, Assisted; Semen; Treatment Outcome; Vagina
PubMed: 33307241
DOI: 10.1016/j.jogoh.2020.102036