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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 -
Journal of Periodontology Sep 2017Chronic prostatitis (CPr) and benign prostatic hyperplasia (BPH) are complex inflammatory conditions for which etiologic determinants are still poorly defined....
BACKGROUND
Chronic prostatitis (CPr) and benign prostatic hyperplasia (BPH) are complex inflammatory conditions for which etiologic determinants are still poorly defined. Periodontitis is caused by subgingival colonizing bacteria in the oral cavity. The causal effect of periodontal disease on prostatic inflammation has not been established. The purpose of this study is to isolate oral pathogens from expressed prostatic secretions of patients with periodontal disease and CPr or BPH.
METHODS
Twenty-four men diagnosed with CPr/BPH participated in the study. A complete periodontal examination consisting of probing depth, bleeding on probing, tooth mobility, gingival index, and plaque index was performed on the men, and prostatic secretion was collected for the study. Dental plaque and prostatic secretion samples were used for analysis of bacterial DNA for Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi), Treponema denticola (Td), and Escherichia coli using reverse transcription-polymerase chain reaction.
RESULTS
Six patients were diagnosed with severe, seven with moderate, and four with mild chronic periodontitis. Seventeen of 24 (70.8%) of the prostatic secretion samples showed one or more of the studied oral pathogens. Nine of 10 BPH and eight of 14 patients with CPr had at least one oral pathogen in their prostatic secretions. Pg was found in both prostatic secretion and plaque samples in six of 17 (35.3%) patients, Td was found in both samples in seven of 15 (46.7%) patients, and E. coli was found in both samples in three of 15 (20%) patients. Pi was detected in all dental plaque samples but not in the prostatic secretion.
CONCLUSION
An association between chronic inflammatory prostate and periodontal diseases has been demonstrated by the presence of similar bacterial DNA in both prostatic secretion and subgingival dental plaque from the same individual.
Topics: Adult; Aged; Aged, 80 and over; Dental Plaque; Escherichia coli; Humans; Male; Middle Aged; Periodontal Index; Periodontitis; Porphyromonas gingivalis; Prevotella intermedia; Prostatic Hyperplasia; Prostatitis; Reverse Transcriptase Polymerase Chain Reaction; Treponema denticola
PubMed: 28548883
DOI: 10.1902/jop.2017.160477 -
International Journal of Cancer Jun 2018One of the hallmarks of cancer cells is the increased ability to acquire nutrients, particularly glucose and glutamine. Proliferating cells need precursors for cell... (Review)
Review
One of the hallmarks of cancer cells is the increased ability to acquire nutrients, particularly glucose and glutamine. Proliferating cells need precursors for cell growth and NADPH reducing equivalents for survival. The principal responsible for glucose uptake is facilitative glucose transporters (GLUTs), which usually are overexpressed in cancer cells. Besides their role in glucose uptake, GLUT transporters are able to transport other compounds such as dehydroascorbic acid or uric acid. They play a major role in tumor progression and cellular processes such as regulated cell death. The prostate gland has the particular characteristic of being more glycolytic than other non-pathological tissues given an accumulation of citrate in the seminal fluid and the inhibition of m-aconitase that affects to tricarboxylic acid cycle. In prostate cancer (PCa), androgens increase glucose uptake, upregulate GLUT transporters such as GLUT1 and GLUT3 and stimulate AMP-activated protein kinase pathway, suggesting a possible connection between glycolytic and androgenic signaling. Interestingly, diabetes is not a risk factor for PCa, as it is in other cancers, while insulin stimulates progression and insulin-like growth factor 1 pathway plays an important role in PCa progression. It was recently found that PCa cells overexpress GLUT4 and, more importantly, that it seems to be related to the castration-resistant prostate cancer (CRPC) phenotype, although little is known about its participation in tumor progression. This review will focus on the role of GLUT transporters along with PCa progression, and the involvement of GLUT4 on CRPC phenotype transition would be considered.
Topics: Adenocarcinoma; Glucose Transport Proteins, Facilitative; Humans; Male; Prostatic Neoplasms
PubMed: 29159872
DOI: 10.1002/ijc.31165 -
Analytical Biochemistry Jul 2023There have been developed many kinds of methods for detecting citrate in body fluids since citrate is very important physiologically and biochemically. In particular,...
There have been developed many kinds of methods for detecting citrate in body fluids since citrate is very important physiologically and biochemically. In particular, determination of citrate concentration in prostatic or seminal fluid is useful in early diagnosis of prostate cancer. Recently, a peroxotitanium complex prepared from titanium tetrachloride and hydrogen peroxide has been shown to have peroxidase-like activity which is greatly inhibited by some hydroxyalkanoic acids. Hence, we established a method for determining citrate concentration in prostatic fluid using selective inhibition of citrate on the catalytic activity of the peroxotitanium complex.
Topics: Male; Humans; Citric Acid; Early Detection of Cancer; Citrates; Prostatic Neoplasms; Body Fluids; Peroxidases
PubMed: 37121535
DOI: 10.1016/j.ab.2023.115152 -
Biomedical Chromatography : BMC Jan 2018Prostate cancer is the most common cancer and one of the leading causes of cancer deaths in men. One of the commonly used approaches to treat metastatic prostate cancer... (Review)
Review
Prostate cancer is the most common cancer and one of the leading causes of cancer deaths in men. One of the commonly used approaches to treat metastatic prostate cancer was via first-generation nonsteroidal anti-androgens (NSAAs), namely flutamide, nilutamide, bicalutamide and topilutamide. Most prostate cancer patients who are initially responsive develop the most aggressive form of disease called castration-resistant prostate cancer. Second-generation NSAA receptor antagonists (enzalutamide, apalutamide and darolutamide) are emerging as additional new options to treat castration-resistant prostate cancer. The objective of this work was to review the literature on the bioanalytical methods for the quantification of first- and second-generation NSAA inhibitors in clinical (human plasma) and preclinical (mouse plasma, rat plasma, urine and tissue homogenates etc.) studies along with relevant case studies for some chosen drugs. Based on the review, it was concluded that the published methodologies using either HPLC or LC-MS/MS are well suited for the quantification of NSAA inhibitors in various biological fluids to delineate pharmacokinetic data.
Topics: Animals; Chromatography, High Pressure Liquid; Humans; Male; Nonsteroidal Anti-Androgens; Prostatic Neoplasms; Tandem Mass Spectrometry
PubMed: 28636139
DOI: 10.1002/bmc.4034 -
Critical Reviews in Oncology/hematology Sep 2019Liquid biopsy can quantify and qualify cell-free (cfDNA) and tumour-derived (ctDNA) DNA fragments in the bloodstream. CfDNA quantification and mutation analysis can be... (Review)
Review
Liquid biopsy can quantify and qualify cell-free (cfDNA) and tumour-derived (ctDNA) DNA fragments in the bloodstream. CfDNA quantification and mutation analysis can be applied to diagnosis, follow-up and therapeutic management as novel oncologic biomarkers. However, some tumor-types release a low amount of DNA into the bloodstream, hampering diagnosis through standard liquid biopsy procedures. Several tumors, as such as brain, kidney, prostate, and thyroid cancer, are in direct contact with other body fluids and may be alternative sources for cfDNA and ctDNA. Non-blood sources of cfDNA/ctDNA useful as novel oncologic biomarkers include cerebrospinal fluids, urine, sputum, saliva, pleural effusion, stool and seminal fluid. Seminal plasma cfDNA, which can be analyzed with cost-effective procedures, may provide powerful information capable to revolutionize prostate cancer (PCa) patient diagnosis and management. In the near future, cfDNA analysis from non-blood biological liquids will become routine clinical practice for cancer patient diagnosis and management.
Topics: Biomarkers, Tumor; Cell-Free Nucleic Acids; Circulating Tumor DNA; DNA Mutational Analysis; Feces; Female; Gene Expression Profiling; Humans; Liquid Biopsy; Male; Medical Oncology; Neoplasms; Pathology, Clinical; Prostatic Neoplasms; Urinalysis
PubMed: 31212145
DOI: 10.1016/j.critrevonc.2019.06.005 -
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 -
Lower Urinary Tract Symptoms May 2019The aim of this study was to investigate the relationship between obstructive sleep apnea syndrome (OSAS) and lower urinary tract symptoms (LUTS) in patients with benign...
OBJECTIVE
The aim of this study was to investigate the relationship between obstructive sleep apnea syndrome (OSAS) and lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia (BPH).
METHODS
This multicenter study was performed on 122 male patients with dyspnea and/or sleep disorder. Patient characteristics were recorded. All patients underwent full-night polysomnography, and the apnea-hypopnea index (AHI) was calculated. LUTS were evaluated using the International Prostate Symptom Score (IPSS) and prostate volume was calculated by transabdominal ultrasonography. Based on the AHI, patients were classified as normal or as having mild, moderate, or severe OSAS. Regression analyses were performed to identify independent predictive factors associated with nocturia.
RESULTS
Severe, moderate, and mild OSAS was present in 53, nine, and 46 patients, respectively, where 14 patients with dyspnea and sleep disorder were classified as normal. There were no significant differences between the severe and mild OSAS groups with regard to age, body mass index, systolic and diastolic blood pressure, smoking history, fluid intake, and serum creatinine and glucose concentrations. However, there was a significant difference between two groups in AHI (P < 0.001), nocturia (P < 0.001), and nocturnal voided volume (P = 0.011). Univariate and multivariate analyses revealed that age, smoking history, and an AHI >15 were independent predictors of nocturia.
CONCLUSIONS
Sleep disorders are thought to be one reason for nocturia and nocturnal polyuria. Thus, OSAS must be considered in BPH patients who predominantly have storage symptoms.
Topics: Adult; Age Factors; Dyspnea; Humans; Male; Middle Aged; Nocturia; Polysomnography; Prostatic Hyperplasia; Prostatism; Retrospective Studies; Risk Factors; Severity of Illness Index; Sleep Apnea, Obstructive; Smoking; Urine
PubMed: 30548821
DOI: 10.1111/luts.12250 -
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