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Analysis of prostatic fluid in prostatic disease.

The current studies of expressed prostatic fluid tend to confirm our previous reported pilot observations of a shift in lactic dehydrogenase (LDH) isoenzymes to a predominance of LDHV in patients with prostatic malignancy. They also suggest a decrease in concentration of acid phosphatase and an increase in concentration of protein in the presence of carcinoma of the prostate. These observations suggest a diffuse metabolic alteration of the prostate in the presence of prostatic carcinoma.

Acid Phosphatase

Subclonal Complete Loss of CDKN1B as a Common Genomic Alteration in Prostate Cancer: Associations With Race and Prostate Cancer Outcomes.

Homozygous biallelic inactivation of CDKN1B is thought to be rare in cancer, including prostate cancer. In the present study, we report that the prevalence of subclonal genomic loss of CDKN1B, especially among self-reported African-American or Black (AA) individuals, has likely been underestimated in primary prostate cancer. Using immunohistochemistry (IHC) for p27 protein and a large cohort of whole tissue sections from radical prostatectomy (N = 412) from AA and European American (EA) individuals, we discovered an unexpectedly high frequency of regions of intratumoral complete p27 protein loss (IPPL) within larger tumor nodules that otherwise showed intact p27 staining that was more prevalent among prostate cancer in AA individuals (18.1%) than EA individuals (12.2%). Regions of IPPL were tightly associated with loss of CDKN1B messenger RNA by in situ hybridization. Furthermore, these focal regions of IPPL were closely linked to CDKN1B genomic loss as detected by next-generation sequencing panel sequencing of laser-captured regions. The detection of IPPL by IHC was associated with ≥pT3 pathologic stage (extraprostatic extension and seminal vesicle involvement) and pN1 (local lymph node involvement) disease; however, when stratified by race, these associations were only significant among AA participants. IPPL was further associated in both univariate and multivariate analyses with the development of biochemical recurrence and metastasis after primary treatment, specifically in AA individuals. The prevalence of p27 genomic alterations in metastatic disease is higher than that of primary prostate cancer in publicly available data sets as well as in our analysis of autopsy specimens via IHC. Overall, subclonal biallelic loss of CDKN1B resulting in complete p27 protein loss is one of the most commonly occurring biallelic tumor suppressor genomic alterations in primary prostate cancer and could contribute to worse prostate cancer outcomes, specifically in AA individuals. Our findings warrant further exploration into the clinical utility of using IHC for p27 loss as a prognostic biomarker.

CDKN1B cancer disparities

Prostatic binding protein. A steriod-binding protein secreted by rat prostate.

Rat prostatic cytosol contains a high concentration of a prostatic binding protein with peculiar steroid-binding properties. Indeed, in spite of a relatively low affinity, charcoal adsorption can be used for its measurement. Furthermore, the binding is not specific for particular steroids and increases very strongly after delipidation. In delipidated cytosol the concentration of the binding site is 3.1 micronmol/g protein and the apparent affinity for pregenolone 1.7 X 10(6) M-1. The high concentration of prostatic binding protein in prostatic fluid shows that this substance is secreted by the prostate. Prostatic binding protein has the following physicochemical characteristics: it is precipitated by ammonium sulfate between 50 and 70% saturation; the elution position from a Sephadex G-100 column corresponds to a molecular weight of 51000; it sediments in sucrose density gradients at 3.7 S and is eluted from DEAE-cellulose columns at about 0.25 M KCl. On polyacrylamide gel electrophoresis the binding activity coincides with the major cytosolic protein band. This band has the same mobility as serum albumin in 7% gels, but a higher mobility in more concentrated gels.

Animals

[Significance of prostatic biopsy in the diagnosis of chronic prostatitis].

It is reported on the importance of the prostate biopsy for the limitation of the prostate neurosis and the real chronic prostatitis. In own patients the tentative diagnosis "chronic prostatitis" could be proved histologically in only 8 out of 30 cases. We think the biopsy necessary in cases of chronic recurrent prostatitis, because the therapy depends extremely on the exact diagnosis and the complicating quota is relatively small in the prostate biopsy.

Adult

A comparison of serum immunoglobulins from patients with non-neoplastic prostates and prostatic carcinoma.

The major immunoglobulin classes were surveyed among 23 patients with carcinoma of the prostate, 14 patients with clinically manifest benign prostatic hyperplasia and 23 healthy, elderly men without evidence of prostatic disease to determine if differences in immunoglobulin levels existed. Levels of IgG,IgA and IgM were determined by single radial immunodiffusion. Serum IgM levels were depressed in patients with all stages of carcinoma of the prostate as compared to levels in controls. These depressions were significant statistically for the tumor group considered as a whole and for patients with stages A and B tumors; the depression of IgM levels in patients with stages C and D tumors bordered on statistical significance. Serum IgG levels were depressed significantly in patients with stages A and B carcinoma of the prostate as compared to controls. Levels in patients with stages C and D lesions exceeded control levels but the difference was not statistically significant. Serum IgA levels in patients with stages A and B tumors were comparable to control levels but levels in patients with stages C and D lesions were significantly higher than controls.

Adult

Androgen levels in the plasma and prostatic tissues of patients with benign hypertrophy and carcinoma of the prostate.

Specific radioimmunoassays for testosterone, dihydrotestosterone (DHT) and androstenedione were carried out to measure the concentrations of the three hormones in the plasma and prostatic tissue of ten patients with benign prostatic hypertrophy (BPH) and ten patients with carcinoma of the prostate. The results indicate that there are no significant differences between the peripheral plasma concentrations of testosterone, DHT and androstenedione in BPH [19.7 +/- 2.6, 2.6 +/- 0.9 AND 5.5 +/- 1.7 (S.E.M.) nmol/l respectively] and in carcinoma [16.9 +/- 2.8, 2.4 +/- 0.5, 4.4 +/- 1.1 nmol/l respectively], (in all cases P greater than 0.1). In contrast, the prostate tissue rations DHT: testosterone (3.59 +/- 0.55 for BPH and 0.66 +/- 0.09 for carcinoma) and androstenedione: testosterone (2.83 +/- 0.38 for BPH and 1.07 +/- 0.16 for carcinoma) are significantly less in carcinoma than in benign hypertrophy ( in all cases P less than 0.01). The accumulation of testosterone in the carcinoma, relative to values found in BPH tissue is, therefore, not associated with changes in the concentrations of androgens in the plasma pool but may be related to local factors and metabolic changes within the prostate.

Aged

[Genes determining virulence factors of Escherichia coli strains isolated from prostate secretions patients with chronic bacterial prostatitis].

UNLABELLED: The aim of the work is to characterize virulence genes of E. coli strains isolated from prostate secretions patients with chronic bacterial prostatitis. MATERIALS AND METHODS: Escherichia coli were isolated from the prostate secretions of men of reproductive age (20-45 years) with chronic bacterial prostatitis using a generally accepted bacteriological method, the type was determined using MALDI-TOF mass spectrometry, virulence genes were PCR and sequencing. RESULTS: The genomes of the studied strains contain genes encoding groups of virulence factors: adhesins, toxins, capsule antigens, siderophores, invasins, and anti-immunity of the macroorganism. Itwas shown that the genes of adhesins, siderophores, and immune system counteraction factors prevailed in E. coli. CONCLUSION: Further studies of E. coli strains using genome-wide sequencing and proteomics technologies are needed. The accumulation of the obtained data will make it possible to use virulence genes as diagnostic markers in patients with chronic prostatitis, indicating the presence of infection.

Humans

Steroid receptors in the human prostate. Detection of tissue-specific androgen binding in prostate cancer.

We have searched for tissue-specific binding of 5alpha-androstan-17beta-ol-3-one (5alpha-dihydrotestosterone; 5alpha-DHT) in cytosols prepared from 25 surgically obtained benign prostatic hypertrophy (BPH) samples and in 3 tissue specimens containing prostate cancer cells. The distinction between steroid-receptor complexes and ligand binding to serum sex hormone-binding globulin (SHBG) was facilitated by combination experiments involving both sucrose gradient ultracentrifugation and agar gel electrophoresis. Gradient analysis of a cytosol prepared from a cervical lymph node (CLN) containing metastatic prostate tissue, revealed both 8-S and 4-S forms of high affinity (charcoal stable) 5alpha-[3H]DHT binding. When electrophoresis was performed on gradient fractions from these zones, anodally migrating steroid-receptor complexes were found only in the 8-S peak, the 4-S region containing radioligand bound to cathodally directed SHBG. In similar experiments with two BPH samples heavily invaded with prostate cancer cells only a single 4-S peak of radioligand binding was detected. Its multicomponent nature was uncovered electrophoretically when, in addition to SHBG, saturable, androgen binding molecules appeared anodally. Their incomplete resolution from SHBG on a gradient might have prevented their identification had this been the only method used. In contrast to the cancer-containing tissues, no saturable 5alpha-[3H]-DHT binding, other than that to SHBG, was detected in any of the BPH samples analysed. It is considered that, of the methods currently available, agar gel electrophoresis may be particularly useful for further investigations into the possible multicomponent nature of androgen binding of tissue origin in the human prostate.

Adenocarcinoma

Comparison of androgen metabolites in benign prostatic hypertrophy (BPH) and normal prostate.

5 alpha-Dihydrotestosterone (DHT) and androstanediols (diols) have been measured in human prostate tissue. DHT levels in surgical specimens of prostate from 8 patients with BPH averaged 5.6 +/- 0.93 S.E. ng/g and were significantly greater than (P less than 0.01) values of 2.1 +/- 0.32 S.E. ng/g in 6 normal prostates obtained post-mortem from males less than 50 yrs old. Androstanediols averaged 2.3 +/- 0.35 S.E. ng/g in the BPH specimens compared to values of 10.2 +/- 2.4 S.E. ng/g in the normal prostates (P less than 0.01). This significantly higher (P less than 0.001) ratio of diols/DHT in the normal (5.1 +/- 0.93 S.E.) compared to the BPH prostate (0.45 +/- 0.08 S.E.) suggests that a decrease in 3-hydroxysteroid oxido-reductase, which converts DHT to diol, may be an important clue to the pathogenesis of BPH.

Androstane-3,17-diol

Studies on carcinogenesis of human prostate. IV. Comparison of normal and neoplastic prostate during long-term explant culture.

Morphologic responses of neoplastic human prostate to long-term explant culture were monitored at serial intervals by LM, TEM and SEM, and compared to normal prostate. Explants were cultured at 37 degrees C in CMRL-1066 supplemented with fetal calf serum and antibiotics. At 0-time culture, normal prostate of young adult males obtained at immediate autopsy, consisted of glandular spaces and ducts lined by columnar to cuboidal secretory epithelial cells and basal cells embedded in fibromuscular stroma. Neoplastic tissue was obtained surgically by transurethral resection (TUR), and consisted of stroma widely infiltrated by well-to moderately-differentiated tumor cells arranged in variable sized, gland-like structures. Secretory activity was evident; basal cells were absent in these glands. During early periods of culture up to several weeks, secretory cells of normal prostate became necrotic. Basal cells remained viable, repopulated acinar structures and epithelialized explant surfaces. At these sites, basal cells, or their derivatives, formed a multicellular epithelium. Exaggerated intercellular spaces separated cells, and synthesis of mucus-like material was seen. Epithelial characteristics included microvilli, junctional complexes, and basal lamina. In marked contrast, tumor cells covered explant surfaces forming an irregular, disorganized layer of squamous-like cells with elongated nuclei and prominent nucleoli. Microvilli, junctional complexes, and basal lamina were poorly developed or absent. Intercellular attachments appeared tenous. Some tumor cells accumulated lipid; synthesis of mucus-like material was not seen. At later intervals of culture up to 10 weeks, synthesis of mucus-like material by basal cells, or their derivatives, declined. Surface cells of neoplastic prostate gradually became more anaplastic in appearance; cells contacted neighboring cells with pseudopodia and filopodia.

Adenocarcinoma

Scanning electron microscopy of human prostatic corpora amylacea and corpora calculi, and prostatic calculi.

Ultrastructural studies of human prostatic corpora amylacea and corpora calculi, and prostatic calculi were conducted in order to delineate their etiology and pathogenesis. Scanning electron microscopy was employed in conjunction with histology and transmission electron microscopy in the study of prostatic tissues and concretions obtained from 21 individuals. Results confirmed that desquamated acinar cells contribute to the formation and growth of corpora amylacea. A variation in density of the matrix of the matrix of the corpora produces a laminated structure. The deposition of hydroxyapatite crystallites in corpora amylacea leads to the formation of corpora calculi. Further growth and mineralization of corpora calculi lead to the development of the more clinically significant prostatic calculi. Small spherical aggregates (from 0.5 to 5 micron in diameter) of hydroxyapatite crystallites are a prevalent constituent of the corpora and prostatic calculi. Similar spherical aggregates of hydroxyapatite crystallites have also been identified in urinary calculi and other pathologic tissues suggesting similar mechanisms of mineral precipitation.

Calculi

Androgens and estrogens in the plasma and prostatic tissue of normal dogs and dogs with benign prostatic hypertrophy.

The endogenous concentrations of certain androgens and estrogens have been quantified in the plasma and prostatic tissue from normal dogs and dogs with benign prostatic hypertrophy (BPH). In the tissue and plasma from both dog populations, the level of estrone was higher than that of estradiol. The concentration of testosterone in the tissue and plasma of both normal dogs and dogs exceeded the concentration of either estrogen. Prostatic levels of dihydrotestosterone greatly exceeded that of testosterone. A comparison of normal dogs and dogs with BPH revealed that in both the plasma and prostatic tissue the concentrations of estradiol and estrone were significantly elevated (P less tha 0.05) in the BPH dogs. Plasma and prostatic levels of testosterone did not differ between the two groups; however, the concentration of dihydrotestosterone in hyperplastic glands was approximately 4 times greater than normal.

Androgens

Optimizing prostate biopsy decision making - (MUSIC-screen): A 1:1 randomized controlled trial comparing micro-ultrasound versus multiparametric magnetic resonance imaging for prostate cancer diagnosis.

BACKGROUND: Micro-ultrasound (microUS) represents a potential alternative to multiparametric magnetic resonance (mpMRI) in guiding prostate biopsy, with level 1 evidence demonstrating non-inferiority to detect Grade Group &#x2265;2 (GG&#xa0;&#x2265;&#xa0;2) prostate cancer in biopsy-na&#xef;ve men. However, a critical gap remains in the screening pathway, in which imaging is needed to identify men at risk and determine whether biopsy is warranted. METHODS: MUSIC-Screen is a phase 3, open-label, noninferiority 1:1 randomized controlled trial evaluating microUS as an alternative imaging compared to mpMRI for determining the need for prostate biopsy in biopsy- and imaging- na&#xef;ve men at risk for GG&#xa0;&#x2265;&#xa0;2. A total of 1284 men will be randomized to undergo either microUS or mpMRI. Men with PRI-MUS 3-5 or PI-RADS 3-5 lesion will undergo targeted and systematic biopsy. Men with negative imaging and PSA density&#xa0;&#x2265;&#xa0;0.15 will undergo systematic biopsy, while those with PSA density&#xa0;<&#xa0;0.15 will defer biopsy. RESULTS: The primary outcome is GG&#xa0;&#x2265;&#xa0;2 detection in each study arm. The primary hypothesis is that microUS is non-inferior to mpMRI for screening and detection of GG&#xa0;&#x2265;&#xa0;2. Secondary objectives include comparison of GG&#xa0;&#x2265;&#xa0;2 detection rates in targeted cores among patients with PRI-MUS or PI-RADS scores of 3-5, proportion of men who defer biopsy but are diagnosed with GG&#xa0;&#x2265;&#xa0;2 within 8&#xa0;years, assessment of the negative predictive value of each imaging modality, and health economic analyses. CONCLUSION: MUSIC-Screen will determine whether microUS can be used as an imaging modality to inform biopsy decision making that is non-inferior to mpMRI for GG&#xa0;&#x2265;&#xa0;2 prostate cancer detection. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06626022.

Humans

Inhibition of leukocyte migration by extracts of malignant prostatic tissue and correlation of degree of in vitro sensitization to clinical responsiveness in prostatic cancer patients.

In an attempt to evaluate the degree of in vitro cellular sensitization to tumor and its relationship to clinical responsiveness, direct leukocyte migration tests were carried out in patients with varying degrees of adenocarcinoma of the prostate employing pooled allogeneic extracts of normal, benign, and malignant prostatic tissue as a source of antigen. Cell-mediated immunity to presumably common prostatic tumor associated antigens was observed. The degree of sensitization of clinically significant specific reactivity of the patients' leukocytes to malignant prostatic tissue was greatest in patients with localized disease, low-grade tumor, and clinically inactive disease than in patients with advanced disease, high-grade tumor, and clinically active disease. Evaluation of the possible correlation of specific reactivity to malignant prostatic tissue as a prognostic index of clinical responsiveness revealed a positive correlation with the degree of sensitization in 3 (43 per cent) of 7 patients. Correlation in 4 patients was questionable because of observations of "stimulation" of migration rather than inhibition, suggested by some to be reflective of weak sensitization to tumor. Evaluation of a larger patient population as well as a prospective study of the relationship of the degree of sensitization and clinical responsiveness will be necessary before any definitive conclusions may be drawn regarding the present observations.

Adenocarcinoma

3-Alpha-androstanediol and prostatic growth: comparison of 3-alpha-androstanediol formation in prostates from 8 species including man and dog.

To determine whether the formation of 3-alpha-androstanediol is critical for androgen-mediated growth of the prostate the conversion of dihydrotestosterone to 3-alpha-androstanediol was assessed in homogenates of 60 normal prostates from 8 species. Rates (nmol. times gm. tissue(-1) times hour(-1)) in the presence of reduced nicotinamide adenine dinucleotide phosphate as cofactor were as follows: dog 271, mouse 200, rat 160, opossum 109, rabbit 24, guinea pig 13, man 11 and cat 9. There was no correlation between prostate size and 3-alpha-androstanediol formation in the entire group. Therefore, either differences in the response to 3-alpha-androstanediol within the prostate or variations in the metabolism of 3-alpha-androstanediol must be more important than the rate of its formation for the development of prostatic hypertrophy in the dog.

Androstane-3,17-diol

The androgenic regulation of prostate proteins with a high affinity for deoxyribonucleic acid. Evidence for a prostate deoxyribonucleic acid-unwinding protein.

1. When testosterone is injected into castrated rats in vivo, a significant increase in the incorporation of [35S]methionine into prostate proteins may be detected under conditions in vitro. 2. Studies based on DNA-cellulose chromatography show that the synthesis of prostate proteins with a high affinity for DNA is particularly enhanced by androgenic stimulation. 3. These changes in protein synthesis are negated when the anti-androgen, cyproterone acetate, is administered concomitantly with testosterone in vivo. 4. Two assays were developed for measuring the strand separation of prostate DNA; first, the retention of 3H-labelled native DNA on nitrocellulose membranes, and second, the activation of native DNA as a template for 9S prostate DNA polymerase. On the basis of these criteria, DNA-unwinding activity is present in the prostate gland and it is regulated by androgens in a steroid-and tissue-specific manner. 5. The results are discussed in the context of the mechanism of action of androgens, particularly since the changes provoked in DNA-unwinding activity by androgens precede the onset of DNA replication and mitosis.

Animals

Carcinoma of the prostate. II. Serum activity of acid phosphatase, prostatic acid phosphatase, LDH and its isoenzymes.

In 25 patients with carcinoma of the prostate (CaP) T3 and in a comparative group of 18 patients with BPH the serum enzymes of AP, tartrate labile AP, LDH, and iso-LDH were investigated simultaneously in basal conditions and after standardized transrectal prostatic biopsy. AP, PAP as well as LDH were shown to be of small diagnostic aid. The reaction of serum enzyme levels following the standardized prostatic biopsy was the same in both CaP and BPH patients. In studying LDH-isoenzymes, we found that the third fraction was elevated in almost all patients. This change is apparently not of prostatic origin, and we could not attribute it to the concomitant diseases found in some patients.

Acid Phosphatase

Prostatic secretion leukocyte studies in non-bacterial prostatitis (prostatosis).

Non-bacterial prostatitis is a common affliction among men and lacks objective criteria for clear identification. We studied 43 consecutive patients and 20 normal controls for the presence of bacteria and quantitation of prostatic secretion leukocytes. Significantly greater numbers of macrophages per volume of prostatic secretion were found in the patients. Multiple observations of such increased leukocyte proliferation could be used to establish true prostatic inflammation.

Adolescent