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Asian Journal of Andrology Sep 2006To investigate the risk factors for prostatic inflammation extent and infection in patients with benign prostatic hyperplasia (BPH) so as to manage prostatic...
AIM
To investigate the risk factors for prostatic inflammation extent and infection in patients with benign prostatic hyperplasia (BPH) so as to manage prostatic inflammation more efficiently.
METHODS
Sixty patients with BPH undergoing TURP between September 2005 and December 2005 in West China Hospital of Sichuan University were studied. Prostate fluid (PF) was collected for the measurement of secretory IgA (SIgA) and complement 3 (C3). Prostate tissue were collected for testing bacterial 16S rDNA by real-time PCR, examining SIgA in the tissue and examining the inflammation. The possible clinical and immune risk factors for prostatic inflammation or infection were analyzed by using the logistic regression method.
RESULTS
Abnormal white blood cell count in urinalysis, prostatic infection and a high concentration of C3 in PF are the risk factors for prostatic inflammation extent (P = 0.025, 0.034 and 0.035, respectively and odds ratio [OR] = 18.269, 8.284 and 1.508, respectively). Risk factors for prostatic infection include the C3 concentration and the concentration of SIgA in PF (P = 0.003 and 0.013, respectively, and OR=1.645 and 0.993, respectively).
CONCLUSION
The present study suggests that prostatic inflammation is associated with urinary tract infection, prostatic infection and the activated complement and that prostatic infection is associated with the activated complement and downregulated mucosal immunity in prostates of the patients with BPH. It is also suggested that individual immune regulation should be considered in the treatment of prostatic inflammation and infection of patients with BPH.
Topics: Bacteria; China; DNA, Ribosomal; Humans; Infections; Inflammation; Leukocyte Count; Male; Patient Selection; Prostate; Prostatic Hyperplasia; RNA, Ribosomal, 16S; Regression Analysis; Risk Factors; Transurethral Resection of Prostate
PubMed: 16751994
DOI: 10.1111/j.1745-7262.2006.00188.x -
European Journal of Human Genetics :... Sep 2013Prostate cancer (PCa) is a worldwide disease that affects a large number of males. Although prostate-specific antigen (PSA) screening is used, the specificity is... (Meta-Analysis)
Meta-Analysis Review
Prostate cancer (PCa) is a worldwide disease that affects a large number of males. Although prostate-specific antigen (PSA) screening is used, the specificity is limited. This study analyzes the sensitivity and specificity of adenomatous polyposis coli (APC) methylation for PCa detection in body fluids and tissues. Combining search results from PubMed and Embase, 19 studies were included, 5 involving body fluids and 14 involving prostate tissue, with 2344 subjects. In body fluid subgroups, the pooled sensitivity and specificity was 0.53 (95% confidence interval (CI): 0.28-0.78) and 0.92 (95% CI: 0.86-0.95), respectively. From tissue studies, the results presented as 0.84 (95% CI: 0.70-0.92) and 0.91 (95% CI: 0.77-0.97). To confirm the results, we conducted a further analysis by removing studies which introduced high heterogeneity due to the type of cases and controls. The same degree of sensitivity and specificity was presented in two subgroups (urine: sensitivity 0.46, 95% CI: 0.39-0.53; specificity 0.87, 95% CI: 0.64-0.96; tissue: sensitivity 0.87, 95% CI: 0.72-0.94; specificity 0.89, 95% CI: 0.68-0.97). In addition, analysis of the interaction between APC methylation and PCa showed strong association in the whole data set (odds ratio (OR)=24.91, 95% CI: 12.86-48.24, I(2)=72.5%). Pooling the same two main subgroups (tissue/fluid) gave a pooled OR of 33.54 (95% CI: 14.88-75.59; I(2)=70.7%) and 8.20 (95% CI: 2.84-23.74, I(2)=64.2%), respectively. From this study, the results suggest that APC promoter methylation may be the potential testing for PCa diagnosis and provide a new viewpoint in the treatment of PCa.
Topics: Adenomatous Polyposis Coli Protein; Case-Control Studies; DNA Methylation; Genetic Association Studies; Humans; Male; Promoter Regions, Genetic; Prostatic Neoplasms; Sensitivity and Specificity
PubMed: 23299921
DOI: 10.1038/ejhg.2012.281 -
The Journal of Urology Sep 2004We reviewed the current literature on mechanisms involved in the pathogenesis of prostatitis/chronic pelvic pain syndrome (CPPS). (Review)
Review
PURPOSE
We reviewed the current literature on mechanisms involved in the pathogenesis of prostatitis/chronic pelvic pain syndrome (CPPS).
MATERIALS AND METHODS
A literature review for the years 1966 to 2003 was performed using the MEDLINE database of the United States National Library of Medicine.
RESULTS
National Institutes of Health categories I and II prostatitis result from identifiable prostatic infections, whereas patients with category IV are asymptomatic. The majority of symptomatic cases are category III or chronic prostatitis (CP)/CPPS. The etiology of CP/CPPS is unknown. The traditional marker of inflammation, namely white blood cells in prostatic fluids, does not correlate with the predominant symptom of pelvic pain. An imbalance toward increased proinflammatory and decreased anti-inflammatory cytokines has been implicated and a few studies have shown some correlation of this with pelvic pain. The imbalance in some men may result from polymorphisms at the cytokine loci. An autoimmune process may be involved and experimental evidence indicates that this can be under hormonal influence. Recent findings include possible defects in the androgen receptor. The prostate may not even be the source of the symptoms. Pelvic pain also correlates with the neurotrophin nerve growth factor implicated in neurogenic inflammation and central sensitization. Finally, psychological stress may produce measurable biochemical changes and influence the other processes. The role of normal prostatic bacterial flora in inciting the inflammatory response has also been reconsidered.
CONCLUSIONS
The symptoms of CP/CPPS appear to result from an interplay between psychological factors and dysfunction in the immune, neurological and endocrine systems.
Topics: Animals; Autoimmune Diseases; Chronic Disease; Cytokines; Gonadal Steroid Hormones; Humans; Inflammation Mediators; Male; Nervous System; Pelvic Pain; Prostatitis; Stress, Psychological
PubMed: 15310980
DOI: 10.1097/01.ju.0000136002.76898.04 -
Journal of Clinical Pathology Jan 2006Mutations in mitochondrial DNA are frequent in cancer and the accompanying mitochondrial dysfunction and altered intermediary metabolism might contribute to, or signal,... (Review)
Review
Mutations in mitochondrial DNA are frequent in cancer and the accompanying mitochondrial dysfunction and altered intermediary metabolism might contribute to, or signal, tumour pathogenesis. The metabolism of human prostate peripheral zone glandular epithelial cells is unique. Compared with many other soft tissues, these glandular epithelial cells accumulate high concentrations of zinc, which inhibits the activity of m-aconitase, an enzyme involved in citrate metabolism through Krebs cycle. This causes Krebs cycle truncation and accumulation of high concentrations of citrate to be secreted in prostatic fluid. The accumulation of zinc also inhibits terminal oxidation. Therefore, these cells exhibit inefficient energy production. In contrast, malignant transformation of the prostate is associated with an early metabolic switch, leading to decreased zinc accumulation and increased citrate oxidation. The efficient energy production in these transformed cells implies increased electron transport chain activity, increased oxygen consumption, and perhaps, excess reactive oxygen species (ROS) production compared with normal prostate epithelial cells. Because ROS have deleterious effects on DNA, proteins, and lipids, the altered intermediary metabolism may be linked with ROS production and accelerated mitochondrial DNA mutations in prostate cancer.
Topics: DNA, Mitochondrial; DNA, Neoplasm; Genome; Humans; Male; Mutation; Prostatic Neoplasms; Reactive Oxygen Species
PubMed: 16394275
DOI: 10.1136/jcp.2005.027664 -
Journal of Zhejiang University.... Jan 2014Prostate cancer (PCa) incidence and mortality have decreased in recent years. Nonetheless, it remains one of the most prevalent cancers in men, being a disquieting cause... (Review)
Review
Prostate cancer (PCa) incidence and mortality have decreased in recent years. Nonetheless, it remains one of the most prevalent cancers in men, being a disquieting cause of men's death worldwide. Changes in many cell signaling pathways have a predominant role in the onset, development, and progression of the disease. These include prominent pathways involved in the growth, apoptosis, and angiogenesis of the normal prostate gland, such as androgen and estrogen signaling, and other growth factor signaling pathways. Understanding the foundations of PCa is leading to the discovery of key molecules that could be used to improve patient management. The ideal scenario would be to have a panel of molecules, preferably detectable in body fluids, that are specific and sensitive biomarkers for PCa. In the early stages, androgen deprivation is the gold standard therapy. However, as the cancer progresses, it eventually becomes independent of androgens, and hormonal therapy fails. For this reason, androgen-independent PCa is still a major therapeutic challenge. By disrupting specific protein interactions or manipulating the expression of some key molecules, it might be possible to regulate tumor growth and metastasis formation, avoiding the systemic side effects of current therapies. Clinical trials are already underway to assess the efficacy of molecules specially designed to target key proteins or protein interactions. In this review, we address that recent progress made towards understanding PCa development and the molecular pathways underlying this pathology. We also discuss relevant molecular markers for the management of PCa and new therapeutic challenges.
Topics: Antineoplastic Agents; Biomarkers, Tumor; Humans; Male; Models, Biological; Molecular Targeted Therapy; Neoplasm Proteins; Prostatic Neoplasms
PubMed: 24390742
DOI: 10.1631/jzus.B1300106 -
Translational Research : the Journal of... Nov 2018Liquid biopsies examine tumor cells or tumor genomic content in circulating fluids. In advanced prostate cancer which metastasizes frequently to the bone, it is... (Review)
Review
Liquid biopsies examine tumor cells or tumor genomic content in circulating fluids. In advanced prostate cancer which metastasizes frequently to the bone, it is difficult to evaluate underlying and evolving genomic heterogeneity of skeletal metastases for effecting clinical care for which reason liquid biopsies offer an alternate approach. In this review, we will summarize the current state of a wide variety of liquid biopsy-based biomarker assays currently being investigated and developed for managing prostate cancer. We will also highlight technical and clinical challenges and opportunities for translating liquid biopsies into clinical applications.
Topics: Biomarkers; Cell-Free Nucleic Acids; Humans; Liquid Biopsy; Male; Neoplasm Staging; Neoplastic Cells, Circulating; Prostatic Neoplasms
PubMed: 29936077
DOI: 10.1016/j.trsl.2018.05.004 -
PloS One 2015Angiotensin-converting enzyme (ACE), which metabolizes many peptides and plays a key role in blood pressure regulation and vascular remodeling, as well as in...
BACKGROUND
Angiotensin-converting enzyme (ACE), which metabolizes many peptides and plays a key role in blood pressure regulation and vascular remodeling, as well as in reproductive functions, is expressed as a type-1 membrane glycoprotein on the surface of endothelial and epithelial cells. ACE also presents as a soluble form in biological fluids, among which seminal fluid being the richest in ACE content - 50-fold more than that in blood.
METHODS/PRINCIPAL FINDINGS
We performed conformational fingerprinting of lung and seminal fluid ACEs using a set of monoclonal antibodies (mAbs) to 17 epitopes of human ACE and determined the effects of potential ACE-binding partners on mAbs binding to these two different ACEs. Patterns of mAbs binding to ACEs from lung and from seminal fluid dramatically differed, which reflects difference in the local conformations of these ACEs, likely due to different patterns of ACE glycosylation in the lung endothelial cells and epithelial cells of epididymis/prostate (source of seminal fluid ACE), confirmed by mass-spectrometry of ACEs tryptic digests.
CONCLUSIONS
Dramatic differences in the local conformations of seminal fluid and lung ACEs, as well as the effects of ACE-binding partners on mAbs binding to these ACEs, suggest different regulation of ACE functions and shedding from epithelial cells in epididymis and prostate and endothelial cells of lung capillaries. The differences in local conformation of ACE could be the base for the generation of mAbs distingushing tissue-specific ACEs.
Topics: Antibodies, Monoclonal; Endothelial Cells; Epididymis; Epitope Mapping; Humans; Lung; Male; Peptidyl-Dipeptidase A; Prostate; Semen
PubMed: 26600189
DOI: 10.1371/journal.pone.0143455 -
Molecular Cancer May 2016Prostate cancer, the second most frequently diagnosed cancer in males worldwide, is estimated to be diagnosed in 1.1 million men per year. Introduction of PSA testing... (Review)
Review
Prostate cancer, the second most frequently diagnosed cancer in males worldwide, is estimated to be diagnosed in 1.1 million men per year. Introduction of PSA testing substantially improved early detection of prostate cancer, however it also led to overdiagnosis and subsequent overtreatment of patients with an indolent disease. Treatment outcome and management of prostate cancer could be improved by the development of non-invasive biomarker assays that aid in increasing the sensitivity and specificity of prostate cancer screening, help to distinguish aggressive from indolent disease and guide therapeutic decisions. Prostate cancer cells release miRNAs into the bloodstream, where they exist incorporated into ribonucleoprotein complexes or extracellular vesicles. Later, cell-free miRNAs have been found in various other biofluids. The initial RNA sequencing studies suggested that most of the circulating cell-free miRNAs in healthy individuals are derived from blood cells, while specific disease-associated miRNA signatures may appear in the circulation of patients affected with various diseases, including cancer. This raised a hope that cell-free miRNAs may serve as non-invasive biomarkers for prostate cancer. Indeed, a number of cell-free miRNAs that potentially may serve as diagnostic, prognostic or predictive biomarkers have been discovered in blood or other biofluids of prostate cancer patients and need to be validated in appropriately designed longitudinal studies and clinical trials. In this review, we systematically summarise studies investigating cell-free miRNAs in biofluids of prostate cancer patients and discuss the utility of the identified biomarkers in various clinical scenarios. Furthermore, we discuss the possible mechanisms of miRNA release into biofluids and outline the biological questions and technical challenges that have arisen from these studies.
Topics: Biological Transport; Biomarkers, Tumor; Body Fluids; Disease Management; Extracellular Vesicles; Gene Expression Profiling; Genetic Testing; Humans; Male; MicroRNAs; Predictive Value of Tests; Prognosis; Prostatic Neoplasms; Transcriptome
PubMed: 27189160
DOI: 10.1186/s12943-016-0523-5 -
Histochemistry and Cell Biology Jul 2019Prostate autonomic and sensory axons control glandular growth, fluid secretion, and smooth muscle contraction and are remodeled during cancer and inflammation....
Prostate autonomic and sensory axons control glandular growth, fluid secretion, and smooth muscle contraction and are remodeled during cancer and inflammation. Morphogenetic signaling pathways reawakened during disease progression may drive this axon remodeling. These pathways are linked to proliferative activities in prostate cancer and benign prostate hyperplasia. However, little is known about which developmental signaling pathways guide axon investment into prostate. The first step in defining these pathways is pinpointing when axon subtypes first appear in prostate. We accomplished this by immunohistochemically mapping three axon subtypes (noradrenergic, cholinergic, and peptidergic) during fetal, neonatal, and adult stages of mouse prostate development. We devised a method for peri-prostatic axon density quantification and tested whether innervation is uniform across the proximo-distal axis of dorsal and ventral adult mouse prostate. Many axons directly interact with or innervate neuroendocrine cells in other organs, so we examined whether sensory or autonomic axons innervate neuroendocrine cells in prostate. We first detected noradrenergic, cholinergic, and peptidergic axons in prostate at embryonic day (E) 14.5. Noradrenergic and cholinergic axon densities are uniform across the proximal-distal axis of adult mouse prostate while peptidergic axons are denser in the periurethral and proximal regions. Peptidergic and cholinergic axons are closely associated with prostate neuroendocrine cells whereas noradrenergic axons are not. These results provide a foundation for understanding mouse prostatic axon development and organization and, provide strategies for quantifying axons during progression of prostate disease.
Topics: Animals; Axons; Male; Mice; Mice, Inbred C57BL; Prostate
PubMed: 30976911
DOI: 10.1007/s00418-019-01784-6 -
Archives of Biochemistry and Biophysics Jul 2007Human prostate glandular epithelial cells have the unique capability of accumulating high levels of zinc. This is essential to inhibit m-aconitase activity so that... (Review)
Review
Human prostate glandular epithelial cells have the unique capability of accumulating high levels of zinc. This is essential to inhibit m-aconitase activity so that citrate can accumulate for secretion into prostatic fluid, which is a major function of the prostate gland. As a result, the Krebs cycle is truncated with the consequence of the lost ATP production that would result from citrate oxidation. The cellular accumulation of zinc also inhibits mitochondrial terminal oxidation and respiration. In addition to these metabolic effects, zinc accumulation exhibits anti-proliferative effects via its induction of mitochondrial apoptogenesis. Zinc accumulation also inhibits the invasive/migration activities in malignant prostate cells. The anti-proliferative effects and the effects on invasion and migration occur through zinc activation of specific intracellular signaling pathways. Consequently, these effects impose anti-tumor actions by zinc. The ability of prostate cells to accumulate zinc is due to the expression and activity of the zinc uptake transporter, ZIP1. To avoid the anti-tumor effects of zinc, in prostate cancer the malignant prostate cells exhibit a silencing of ZIP1 gene expression accompanied by a depletion of cellular zinc. Therefore we regard ZIP1 as a tumor suppressor gene in prostate cancer. In addition to prostate cells, similar tumor suppressor effects of zinc have been identified in several other types of tumors.
Topics: Animals; Antineoplastic Agents; Apoptosis; Biological Transport; Genes, Tumor Suppressor; Humans; Male; Mice; Neoplasm Invasiveness; Neoplasm Metastasis; Prostate; Prostatic Neoplasms; Signal Transduction; Zinc
PubMed: 17400177
DOI: 10.1016/j.abb.2007.02.033