Identification of metastatic cell nucleus in human prostate cancer by electron microscopy.

Aim: Metastatic prostate cancer is responsible for a large proportion of deaths worldwide. The aim of this study was to identify metastatic cells and determine if stromal invasion by cancer cells differs from those during metastasis.

Methods & Results: Tissue biopsy/prostatectomy samples, visualized by transmission electron microscopy, identified that metastatic cells are a lineage of stem cells, which have dedifferentiated into cancerous columnar/cuboidal cells.

Electron Microscopic Analysis of Stem Cells in Human Prostate Cancer, Including Inverted Capsule Embedding Methods for Archival Sections and Falcon Films for Prostate Cancer Cell Lines.

Background/aim: Identification of prostatic stem cells in primary prostate tissue sections, organ cultures of prostate and cell lines requires a range of techniques that allows characterization of stem cells for their potential use in the treatment of patients. Isolated cells usually round-up and develop changes in shape, size and cellular characteristics. The aim of this study was to provide a range of methods for identifying prostatic stem cells and characterizing them with regard to ultrastructure, nuclear morphology, cytoplasmic organelles, and/or expression stem cell marker CD133.

Identification of Two Types of Stem Cells in Methylene Blue-stained Sections of Untreated and Diethylstilbestrol-treated Human Prostate Cancer and Their Characterization by Immunogold Localization of CD133.

Background: The basal compartment of the prostatic acinus harbors stem and basal cells, whereas the luminal compartment contains cuboidal and columnar cells. Mutation in the genes of stem cells is required for benign (normal) prostate to develop into prostatic adenocarcinoma. Stem/basal cells survive androgen deprivation therapy in humans and castrated mice to repopulate glandular cells by proliferation when stimulated by androgen.

Matrix metalloproteinase and heparin-stimulated serine proteinase activities in post-prostate massage urine of men with prostate cancer.

Proteinases secreted by the prostate gland have a reproductive function in cleaving proteins in the ejaculate and in the female reproductive tract, but some may have a fundamental role in disease and pathological processes including cancer. The purpose of this study was to determine if there were differences in proteinase activities in urine samples collected following prostate massage of men positive (CaP) or negative (no evidence of malignancy, NEM) for biopsy determined prostate cancer. Matrix metalloproteinase (MMP) and serine proteinase activities were detected using protein substrate zymography.

Concurrent Androgen and Estrogen Ablation and Inhibition of Steroid Biosynthetic Enzyme Treatment for Castration-resistant Prostate Cancer.

Background/aim: About 80 to 90% of prostate cancer (PCa) is androgen-dependent at diagnosis, but patients ultimately develop castration-resistant prostate cancer (CRPC), which is usually not amenable to androgen deprivation (ablation) therapy (ADT). Patients with CRPC usually succumb to death in less than 5 years and there is no cure. Here, we investigated reasons for ADT failure.

Induction of a heparin-stimulated serine proteinase in sex accessory gland tumors of the Lobund-Wistar rat.

Induction of new proteinase activities that may process growth factors, modify cell surface receptors, cleave extracellular matrix proteins, etc. is considered fundamental in carcinogenesis. The purpose of this study was to characterize a novel proteinase activity induced in sex accessory gland cancers (about 70% in seminal vesicles) of adult male Lobund-Wistar rats by a single injection of N-nitroso-N-methylurea (NMU; 25mg/kg) followed by implanted testosterone propionate (45mg in silastic tubing every 2months) treatment for 10-14months.

Prediction of immune surveillance responsive metastatic prostate cancer in pelvic lymph node and emergence of surveillance unresponsive/resistant metastatic cells.

Background: Immune cells (lymphocytes and macrophages) provide the microenvironment for immune surveillance of metastatic prostate cancer (PCa) cells in pelvic lymph nodes. We have hypothesized that degeneration and/or apoptosis of metastatic PCa cells in pelvic lymph nodes can distinguish between aggressive and non-aggressive metastatic disease in patients. Our objective was to define the relationship between metastatic cell lysis and the presence of immune cells.

Characterization of prostate cancer in needle biopsy by cathepsin B, cell proliferation and DNA ploidy.

Background: Our objective was to determine localization patterns of three distinct groups of biomarkers (cathepsin B, MIB-1 and DNA ploidy) in prostate needle biopsy sections to establish localization similarities (or differences) in biopsy and retropubic prostatectomy specimens (RPs).

Materials And Methods: Prostate needle biopsy specimens and matched RPs from 47 patients with cancer were evaluated. Biopsy and RP sections were stained with anti-cathepsin B (CB) and anti-stefin (cystatin) A (SA) and for cell proliferation and DNA ploidy.

Patterns, art, and context: Donald Floyd Gleason and the development of the Gleason grading system.

The Gleason grading system is a standard method of assessing prostate cancer. Very little is known, however, about the person behind the system, Donald Floyd Gleason, MD, PhD. Our objective was to construct a biography of Gleason and show how his work advanced prostate cancer diagnosis.

Increased aggressiveness of human prostate PC-3 tumor cells expressing cell surface localized membrane type-1 matrix metalloproteinase (MT1-MMP).

Membrane type-1 matrix metalloproteinase (MT1-MMP) is a multidomain transmembrane endopeptidase with a major role in physiological and pathological processes through proteolysis of extracellular matrix and other pericellular proteins. We examined cell surface function of MT1-MMP in PC-3 human prostate tumor cells selected for metastasis in nude mice (PC-3-LN4), or transfected with the full-length wild-type (WT) MT1-MMP or with the mutant form lacking the cytoplasmic tail (Delta C-MT1-MMP). Enhanced cell surface MT1-MMP was determined by fluorescence-activated cell sorting analysis and evidenced mechanistically by increased activation of proMMP-2 and invasion into type-I collagen gels.

Cathepsin B expression in prostate cancer of native Japanese and Japanese-American patients: an immunohistochemical study.

Background: Japanese-American (J-A) men who have immigrated to the U.S.A.

The effect of dietary supplementation with limonene or myo-inositol on the induction of neoplasia and matrix metalloproteinase and plasminogen activator activities in accessory sex organs of male Lobund-Wistar rats.

Prostate cancer, the most prevalent non-cutaneous cancer in men, is associated with increased age. This suggests that dietary chemopreventive measures could be effective in delaying the onset or decreasing the severity of the disease. We utilized the Lobund-Wistar rat nitrosomethylurea induced, testosterone promoted (NMU-T) model of male sex accessory gland cancer to test the potential chemopreventive effects of myo-inositol and limonene on tumor incidence and associated protease activities.

Cathepsin B expression is similar in African-American and Caucasian prostate cancer patients.

Background: Increased incidence and mortality of prostate cancer (PCa) suggest that U.S. African-American men have more invasive cancer than Caucasian men.

Heterogeneity of cathepsin B and stefin A expression in Gleason pattern 3+3 (score 6) prostate cancer needle biopsies.

Background: There is a significant positive association of increased ratios of cathepsin B to its endogenous inhibitor stefin (cystatin) A in prostatectomy tumors with pelvic lymph node metastases. Needle biopsy diagnosis of prostate cancer is critical in initial treatment selection. The objective was to characterize cathepsin B and stefin A immunostaining patterns in needle biopsies of histologically similar Gleason pattern 3+3 (score 6) foci in relation to pretreatment clinical data.

Elevation of dipeptidylpeptidase iv activities in the prostate peripheral zone and prostatic secretions of men with prostate cancer: possible prostate cancer disease marker.

Purpose: Dipeptidylpeptidase IV (DPIV) is a multifunctional type II plasma membrane glycoprotein with serine-type exopeptidase activity that is secreted by the prostate and increased in prostate cancer. We determined whether changes in DPIV activities in prostatic tissue zones and expressed secretions were associated with the presence of cancer.

Materials And Methods: Expressed prostatic secretion (EPS), and biopsy of the transition (TZ) and peripheral (PZ) zones were collected from men undergoing ultrasound guided prostate biopsy.

Microvessel density as a molecular marker for identifying high-grade prostatic intraepithelial neoplasia precursors to prostate cancer.

Background: Existing clinical data have shown that high-grade prostatic intraepithelial neoplasia (HGPIN) is the most likely precursor to prostate cancer (CaP). Criteria to distinguish HGPIN that progress to CaP from those that do not remain poorly defined. Our objective was to evaluate microvessel density as a molecular marker for distinguishing HGPINs that have the potential of progressing to cancer.

Matrix metalloproteinases in the pathogenesis of estradiol-induced nonbacterial prostatitis in the lateral prostate lobe of the Wistar rat.

Chronic nonbacterial prostatitis develops spontaneously with age in the lateral lobe of the prostate in some strains of rat. Our objective was to examine the role of matrix metalloproteinases (MMP) in the pathogenesis of chronic nonbacterial prostatitis using a chronic estrogen treatment, Wistar rat model (Prostate 12 (1988) 271). Male Wistar rats, 90 days of age (8 rats/group), were castrated and groups were implanted 8 days later with 1 cm silastic tubings containing estradiol 17 beta (E2).

Limited processing of pro-matrix metalloprotease-2 (gelatinase A) overexpressed by transfection in PC-3 human prostate tumor cells: association with restricted cell surface localization of membrane-type matrix metalloproteinase-1.

The expression and activation of matrix metalloproteinases (MMPs) by tumor cells is correlated with progression to invasive and metastatic status. The purpose of this study was to examine the role of increased MMP-2 (gelatinase A) expression in prostate cancer progression utilizing human prostate PC-3 cancer cells that overexpress MMP-2 using gene transfection. PC-3 cells were transfected with pCR-3 vector only and pCR-3 MMP-2 plasmids employing the LipofectAMINE method, and stable transfectants were selected with G418.

Effect of vitamin E deficiency on the growth and secretory function of the rat prostatic complex.

Increased intake of vitamin E has been suggested to be protective against prostate cancer in men, but the effects of vitamin E on prostate growth and function remain poorly defined. The purpose of this study was to determine the effects of vitamin E deficiency on pubertal growth and maturation of the prostate in the rat. Animals were placed on a vitamin E deficient diet at 28 days of age and were followed for 15 and 26 weeks.

Prediction of pelvic lymph node metastasis by the ratio of cathepsin B to stefin A in patients with prostate carcinoma.

Background: Pathologic grade and/or histologic score, extraprostatic extension indicated by invasion of the prostatic capsule, margin, and/or seminal vesicles by prostate cancer cells, serum total prostate-specific antigen (PSA), free PSA, complexed PSA levels and/or their ratios, regional pelvic lymph node metastases, and clinical staging have been used to diagnose and monitor the treatment of prostate carcinoma (PC) patients. The Gleason grading system is also used to grade/score a patient's stage of disease, with lower to higher scores indicating progression of PC. However, Gleason's system cannot be used to distinguish biologically aggressive PCs within a single Gleason score.