Seminal epithelium in prostate biopsy can mimic malignant and premalignant prostatic lesions.

PubMed

Arista-Nasr, J; Trolle-Silva, A; Aguilar-Ayala, E; Martínez-Benítez, B

2016-01-01

In most prostate biopsies, the seminal epithelium is easily recognised because it meets characteristic histological criteria. However, some biopsies can mimic malignant or premalignant prostatic lesions. The aims of this study were to analyse the histological appearance of the biopsies that mimic adenocarcinomas or preneoplastic prostatic lesions, discuss the differential diagnosis and determine the frequency of seminal epithelia in prostate biopsies. We consecutively reviewed 500 prostate puncture biopsies obtained using the sextant method and selected those cases in which we observed seminal vesicle or ejaculatory duct epithelium. In the biopsies in which the seminal epithelium resembled malignant or premalignant lesions, immunohistochemical studies were conducted that included prostate-specific antigen and MUC6. The most important clinical data were recorded. Thirty-six (7.2%) biopsies showed seminal epithelium, and 7 of them (1.4%) resembled various prostate lesions, including high-grade prostatic intraepithelial neoplasia, atypical acinar proliferations, adenocarcinomas with papillary patterns and poorly differentiated carcinoma. The seminal epithelium resembled prostate lesions when the lipofuscin deposit, the perinuclear vacuoles or the nuclear pseudoinclusions were inconspicuous or missing. Five of the 7 biopsies showed mild to moderate cellular atypia with small and hyperchromatic nuclei, and only 2 showed cellular pleomorphism. The patients were alive and asymptomatic after an average of 6 years of progression. The seminal epithelium resembles prostatic intraepithelial neoplasia, atypical acinar proliferations and various types of prostatic adenocarcinomas in approximately 1.4% of prostate biopsies. Copyright © 2015 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Magnetic resonance imaging in the new paradigm for the diagnosis of prostate cancer.

PubMed

Vilanova, J C; Catalá, V

For various reasons, prostate cancer is a major public health problem. It is a very common cancer, but has a very low mortality rate because it comprises two types of disease: one insignificant, indolent, and much more common, and the other aggressive, significant, and much less common. The routine diagnostic approach to prostate cancer has been systematic blind biopsies, which has low detection rates and might detect low risk, insignificant prostate cancer, leading to overdiagnosis and overtreatment of indolent cancers. The possibility of including multiparametric magnetic resonance imaging in the diagnostic management to improve the detection of aggressive cancer while reducing the overdiagnosis of indolent cancer represents a change in the diagnostic management. This article updates knowledge about the diagnostic management of prostate cancer including multiparametric magnetic resonance imaging. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

Genetic and Epigenetic Biomarkers for Recurrent Prostate Cancer After Radiotherapy

DTIC Science & Technology

2014-05-01

complications from surgery as well as risks associated with anesthesia. Moreover, this therapy includes a low risk of urinary incontinence . Major...another type of RT, involves placing radioactive sources into the prostate tissue. Disadvantages of this treatment include the risk of acute urinary ...Molecular mechanisms and clinical applications of angiogenesis. Nature, 2011. 473(7347): p. 298-307. 6. Yao, J.L., et al., Tissue factor and VEGF

The Association between Phosphodiesterase Type 5 Inhibitors and Prostate Cancer: Results from the REDUCE Study.

PubMed

Jamnagerwalla, Juzar; Howard, Lauren E; Vidal, Adriana C; Moreira, Daniel M; Castro-Santamaria, Ramiro; Andriole, Gerald L; Freedland, Stephen J

2016-09-01

Despite routine use of phosphodiesterase type 5 inhibitor to treat erectile dysfunction the role in prostate cancer chemoprevention remains unclear. Only a few studies have explored the link between phosphodiesterase type 5 inhibitor use and prostate cancer. We tested the association between phosphodiesterase type 5 inhibitor and prostate cancer risk in the REDUCE (Reduction by Dutasteride of Prostate Cancer Events) trial. REDUCE was a 4-year multicenter study testing the effect of daily dutasteride on prostate cancer risk in men with prostate specific antigen 2.5 to 10.0 ng/ml and negative biopsy who underwent study mandated biopsies at 2 and 4 years. The association of phosphodiesterase type 5 inhibitor with overall prostate cancer risk and disease grade (Gleason 2-6 and 7-10) was examined using adjusted logistic and multinomial regression analysis. Secondary analysis was performed to explore the association between phosphodiesterase type 5 inhibitor and prostate cancer risk in North American men, given the significantly higher use of phosphodiesterase type 5 inhibitor in these subjects. Phosphodiesterase type 5 inhibitor was not associated with prostate cancer diagnosis (OR 0.90, 95% CI 0.68-1.20, p = 0.476), low grade disease (OR 0.93, 95% CI 0.67-1.27, p = 0.632) or high grade disease (OR 0.85, 95% CI 0.51-1.39, p = 0.508). An inverse trend was seen between phosphodiesterase type 5 inhibitor and prostate cancer diagnosis in North American men but this was not statistically significant (OR 0.67, 95% CI 0.42-1.07, p = 0.091). Phosphodiesterase type 5 inhibitor use was not associated with decreased prostate cancer diagnoses on post-hoc analysis of REDUCE. In North American men, who had much higher baseline use of phosphodiesterase type 5 inhibitor, this treatment was associated with an inverse trend of prostate cancer diagnosis that approached but did not reach statistical significance. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Increasing Early Detection of Prostate Cancer in African American Men through a Culturally Targeted Print Intervention

DTIC Science & Technology

2008-06-01

and brittle bones . 8 INFORM YOUR DOCTOR Certain activities, conditions, and substances can also affect PSA levels, including: • medicines (such as...Growth rates for this type of cancer can vary. Studies have shown that prostate tumors grow at different rates in different people . While some...This is one reason why early detection may be important. • When the cancer spreads beyond the prostate, it becomes more difficult to manage and the

Extraglandular and intraglandular vascularization of canine prostate.

PubMed

Stefanov, Miroslav

2004-03-01

The literature on the vascularization of the canine prostate is reviewed and the clinical significance of prostate morphology is described. Scanning Electron Microscopy (SEM), combined with improved corrosion casting methods, reveal new morphological details that promise better diagnostics and treatment but also require expansion of clinical nomenclature. A proposal is made for including two previously unnamed veins in Nomina Anatomica Veterinaria (NAV). The canine prostate has two lobes with independent vascularization. Each lobe is supplied through the left and right a. prostatica, respectively. The a. prostatica sprouts three small vessels (cranial, middle, and caudal) towards the prostate gland. A. prostatica is a small-size artery whose wall structure is similar to the arteries of the muscular type. V. prostatica is a small-size valved vein. The canine prostate has capsular, parenchymal, and urethral vascular zones. The surface vessels of the capsule are predominantly veins and the diameter of arterial vessels is larger than that of the veins. The trabecular vessels are of two types: direct and branched. The prostate parenchyma is supplied by branches of the trabecular vessels. The periacinary capillaries are fenestrated and form a net in a circular pattern. The processes of the myoepithelial cells embrace both the acins and the periacinar capillaries. In the prostate ductal system. there are spermatozoa. The prostatic part of the urethra is supplied by an independent branch of a. prostatica. The prostatic urethral part is drained by v. prostatica, the vein of the urethral bulb and the ventral prostate veins. M. urethralis begins as early as the urethral prostatic part. The greater part of the white muscle fibers in m. urethralis suggest an enhanced anaerobic metabolism. Copyright 2004 Wiley-Liss, Inc.

A subset of high Gleason grade prostate carcinomas contain a large burden of prostate cancer syndecan-1 positive stromal cells.

PubMed

Sharpe, Benjamin; Alghezi, Dhafer A; Cattermole, Claire; Beresford, Mark; Bowen, Rebecca; Mitchard, John; Chalmers, Andrew D

2017-05-01

There is a pressing need to identify prognostic and predictive biomarkers for prostate cancer to aid treatment decisions in both early and advanced disease settings. Syndecan-1, a heparan sulfate proteoglycan, has been previously identified as a potential prognostic biomarker by multiple studies at the tissue and serum level. However, other studies have questioned its utility. Anti-Syndecan-1 immunohistochemistry was carried out on 157 prostate tissue samples (including cancerous, adjacent normal tissue, and non-diseased prostate) from three independent cohorts of patients. A population of Syndecan-1 positive stromal cells was identified and the number and morphological parameters of these cells quantified. The identity of the Syndecan-1-positive stromal cells was assessed by multiplex immunofluorescence using a range of common cell lineage markers. Finally, the burden of Syndecan-1 positive stromal cells was tested for association with clinical parameters. We identified a previously unreported cell type which is marked by Syndecan-1 expression and is found in the stroma of prostate tumors and adjacent normal tissue but not in non-diseased prostate. We call these cells Prostate Cancer Syndecan-1 Positive (PCSP) cells. Immunofluorescence analysis revealed that the PCSP cell population did not co-stain with markers of common prostate epithelial, stromal, or immune cell populations. However, morphological analysis revealed that PCSP cells are often elongated and displayed prominent lamellipodia, suggesting they are an unidentified migratory cell population. Analysis of clinical parameters showed that PCSP cells were found with a frequency of 20-35% of all tumors evaluated, but were not present in non-diseased normal tissue. Interestingly, a subset of primary Gleason 5 prostate tumors had a high burden of PCSP cells. The current study identifies PCSP cells as a novel, potentially migratory cell type, which is marked by Syndecan-1 expression and is found in the stroma of prostate carcinomas, adjacent normal tissue, but not in non-diseased prostate. A subset of poor prognosis high Gleason grade 5 tumors had a particularly high PCSP cell burden, suggesting an association between this unidentified cell type and tumor aggressiveness. © 2017 Wiley Periodicals, Inc.

Analysis of the Human Prostate-Specific Proteome Defined by Transcriptomics and Antibody-Based Profiling Identifies TMEM79 and ACOXL as Two Putative, Diagnostic Markers in Prostate Cancer

PubMed Central

O'Hurley, Gillian; Busch, Christer; Fagerberg, Linn; Hallström, Björn M.; Stadler, Charlotte; Tolf, Anna; Lundberg, Emma; Schwenk, Jochen M.; Jirström, Karin; Bjartell, Anders; Gallagher, William M.; Uhlén, Mathias; Pontén, Fredrik

2015-01-01

To better understand prostate function and disease, it is important to define and explore the molecular constituents that signify the prostate gland. The aim of this study was to define the prostate specific transcriptome and proteome, in comparison to 26 other human tissues. Deep sequencing of mRNA (RNA-seq) and immunohistochemistry-based protein profiling were combined to identify prostate specific gene expression patterns and to explore tissue biomarkers for potential clinical use in prostate cancer diagnostics. We identified 203 genes with elevated expression in the prostate, 22 of which showed more than five-fold higher expression levels compared to all other tissue types. In addition to previously well-known proteins we identified two poorly characterized proteins, TMEM79 and ACOXL, with potential to differentiate between benign and cancerous prostatic glands in tissue biopsies. In conclusion, we have applied a genome-wide analysis to identify the prostate specific proteome using transcriptomics and antibody-based protein profiling to identify genes with elevated expression in the prostate. Our data provides a starting point for further functional studies to explore the molecular repertoire of normal and diseased prostate including potential prostate cancer markers such as TMEM79 and ACOXL. PMID:26237329

Lower urinary tract symptoms in benign prostatic hyperplasia patients: orchestrated by chronic prostatic inflammation and prostatic calculi?.

PubMed

Kim, Sang Hoon; Jung, Kyu In; Koh, Jun Sung; Min, Ki Ouk; Cho, Su Yeon; Kim, Hyun Woo

2013-01-01

This study aims to examine the relationship between chronic prostatic inflammation and prostatic calculi, and clinical parameters of benign prostatic hyperplasia (BPH). This study was based on 225 patients who underwent transurethral resection of the prostate for BPH. Chronic inflammation was graded as 0 (n = 44), I (n = 54), II (n = 88) or III (n = 39) according to severity. Prostatic calculi were classified into types A (n = 66), B (n = 44), M (n = 77) and N (n = 38). The relationship between inflammation and calculus type was analyzed, and clinical parameters of BPH were compared for each group. There was no correlation between severity of inflammation and calculus type. Prostatic volume increased with the severity of inflammation and showed significant differences between G2, G3 and G0. The International Prostate Symptom Score also increased with increasing inflammation. There was no significant difference between each clinical parameter according to calculus type. Prostatic calculi had no significant association with chronic inflammation and clinical parameters of BPH. Chronic inflammation was associated with the volume of the prostate and storage symptoms; thus, it is not only presumed to be related to the progression of BPH, but may also be one of the causes of lower urinary tract symptoms. Copyright © 2012 S. Karger AG, Basel.

Hedgehog Signaling in Prostate Cancer and Its Therapeutic Implication

PubMed Central

Gonnissen, Annelies; Isebaert, Sofie; Haustermans, Karin

2013-01-01

Activation of Hedgehog (Hh) signaling is implicated in the development and progression of several tumor types, including prostate cancer, which is still the most common non-skin malignancy and the third leading cause of cancer-related mortality in men in industrialized countries worldwide. Several studies have indicated that the Hh pathway plays a crucial role in the development as well as in the progression of this disease to more aggressive and even therapy-resistant disease states. Moreover, preclinical data have shown that inhibition of Hh signaling has the potential to reduce prostate cancer invasiveness and metastatic potential. Clinical trials investigating the benefit of Hh inhibitors in patients with prostate cancer have recently been initiated. However, acquired drug resistance has already been observed in other tumor types after long-term Hh inhibition. Therefore, combining Hh inhibitors with ionizing radiation, chemotherapy or other molecular targeted agents could represent an alternative therapeutic strategy. In this review, we will highlight the role of Hh signaling in the development and progression of prostate cancer and summarize the different therapeutic applications of Hedgehog inhibition. PMID:23880852

Differentiation of prostatitis and prostate cancer using the Prostate Imaging-Reporting and Data System (PI-RADS).

PubMed

Meier-Schroers, Michael; Kukuk, Guido; Wolter, Karsten; Decker, Georges; Fischer, Stefan; Marx, Christian; Traeber, Frank; Sprinkart, Alois Martin; Block, Wolfgang; Schild, Hans Heinz; Willinek, Winfried

2016-07-01

To determine if prostate cancer (PCa) and prostatitis can be differentiated by using PI-RADS. 3T MR images of 68 patients with 85 cancer suspicious lesions were analyzed. The findings were correlated with histopathology. T2w imaging (T2WI), diffusion weighted imaging (DWI), dynamic contrast enhancement (DCE), and MR-Spectroscopy (MRS) were acquired. Every lesion was given a single PI-RADS score for each parameter, as well as a sum score and a PI-RADS v2 score. Furthermore, T2-morphology, ADC-value, perfusion type, citrate/choline-level, and localization were evaluated. 44 of 85 lesions showed PCa (51.8%), 21 chronic prostatitis (24.7%), and 20 other benign tissue such as hyperplasia or fibromuscular tissue (23.5%). The single PI-RADS score for T2WI, DWI, DCE, as well as the aggregated score including and not including MRS, and the PI-RADS v2-score were all significantly higher for PCa than for prostatitis or other tissue (p<0.001). The single PI-RADS score for MRS and the PI-RADS sum score including MRS were significantly higher for prostatitis than for other tissue (p=0.029 and p=0.020), whereas the other parameters were not different. Prostatitis usually presented borderline pathological PI-RADS scores, showed restricted diffusion with ADC≥900mm(2)/s in 100% of cases, was more often indistinctly hypointense on T2WI (66.7%), and localized in the transitional zone (57.1%). An ADC≥900mm(2)/s achieved the highest predictive value for prostatitis (AUC=0.859). Prostatitis can be differentiated from PCa using PI-RADS, since all available parameters are more distinct in cases of cancer. However, there is significant overlap between prostatitis and other benign findings, thus PI-RADS is only suitable to a limited extent for the primary assessment of prostatitis. Restricted diffusion with ADC≥900mm(2)/s is believed to be a good indicator for prostatitis. MRS can help to distinguish between prostatitis and other tissue. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Novel Nine-Exon AR Transcripts (Exon 1/Exon 1b/Exons 2-8) in Normal and Cancerous Breast and Prostate Cells.

PubMed

Hu, Dong Gui; McKinnon, Ross A; Hulin, Julie-Ann; Mackenzie, Peter I; Meech, Robyn

2016-12-27

Nearly 20 different transcripts of the human androgen receptor (AR) are reported with two currently listed as Refseq isoforms in the NCBI database. Isoform 1 encodes wild-type AR (type 1 AR) and isoform 2 encodes the variant AR45 (type 2 AR). Both variants contain eight exons: they share common exons 2-8 but differ in exon 1 with the canonical exon 1 in isoform 1 and the variant exon 1b in isoform 2. Splicing of exon 1 or exon 1b is reported to be mutually exclusive. In this study, we identified a novel exon 1b (1b/TAG) that contains an additional TAG trinucleotide upstream of exon 1b. Moreover, we identified AR transcripts in both normal and cancerous breast and prostate cells that contained either exon 1b or 1b/TAG spliced between the canonical exon 1 and exon 2, generating nine-exon AR transcripts that we have named isoforms 3a and 3b. The proteins encoded by these new AR variants could regulate androgen-responsive reporters in breast and prostate cancer cells under androgen-depleted conditions. Analysis of type 3 AR-GFP fusion proteins showed partial nuclear localization in PC3 cells under androgen-depleted conditions, supporting androgen-independent activation of the AR. Type 3 AR proteins inhibited androgen-induced growth of LNCaP cells. Microarray analysis identified a small set of type 3a AR target genes in LNCaP cells, including genes known to modulate growth and proliferation of prostate cancer ( PCGEM1 , PEG3 , EPHA3 , and EFNB2 ) or other types of human cancers ( TOX3 , ST8SIA4 , and SLITRK3 ), and genes that are diagnostic/prognostic biomarkers of prostate cancer ( GRINA3 , and BCHE ).

Phase I/II prospective trial of cancer-specific imaging using ultrasound spectrum analysis tissue-type imaging to guide dose-painting prostate brachytherapy.

PubMed

Ennis, Ronald D; Quinn, S Aidan; Trichter, Frieda; Ryemon, Shannon; Jain, Anudh; Saigal, Kunal; Chandrashekhar, Sarayu; Romas, Nicholas A; Feleppa, Ernest J

2015-01-01

To assess the technical feasibility, toxicity, dosimetry, and preliminary efficacy of dose-painting brachytherapy guided by ultrasound spectrum analysis tissue-type imaging (TTI) in low-risk, localized prostate cancer. Fourteen men with prostate cancer who were candidates for brachytherapy as sole treatment were prospectively enrolled. Treatment planning goal was to escalate the tumor dose to 200% with a modest de-escalation of dose to remaining prostate compared with our standard. Primary end points included technical feasibility of TTI-guided brachytherapy and equivalent or better toxicity compared with standard brachytherapy. Secondary end points included dose escalation to tumor regions and de-escalated dose to nontumor regions on the preimplant plan, negative prostate biopsy at 2 years, and freedom from biochemical failure. Thirteen of fourteen men successfully completed the TTI-guided brachytherapy procedure for a feasibility rate of 93%. A software malfunction resulted in switching one patient from TTI-guided to standard brachytherapy. An average of 2.7 foci per patient was demonstrated and treated with an escalated dose. Dosimetric goals on preplan were achieved. One patient expired from unrelated causes 65 days after brachytherapy. Toxicity was at least as low as standard brachytherapy. Two-year prostate biopsies were obtained from six men; five (83%) were definitively negative, one showed evidence of disease with treatment effect, and none were positive. No patients experienced biochemical recurrence after a median followup of 31.5 (24-52) months. We have demonstrated that TTI-guided dose-painting prostate brachytherapy is technically feasible and results in clinical outcomes that are encouraging in terms of low toxicity and successful biochemical disease control. Copyright © 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Characterization of adenoviral transduction profile in prostate cancer cells and normal prostate tissue.

PubMed

Ai, Jianzhong; Tai, Phillip W L; Lu, Yi; Li, Jia; Ma, Hong; Su, Qin; Wei, Qiang; Li, Hong; Gao, Guangping

2017-09-01

Prostate diseases are common in males worldwide with high morbidity. Gene therapy is an attractive therapeutic strategy for prostate diseases, however, it is currently underdeveloped. As well known, adeno virus (Ad) is the most widely used gene therapy vector. The aims of this study are to explore transduction efficiency of Ad in prostate cancer cells and normal prostate tissue, thus further providing guidance for future prostate pathophysiological studies and therapeutic development of prostate diseases. We produced Ad expressing enhanced green fluorescence protein (EGFP), and characterized the transduction efficiency of Ad in both human and mouse prostate cancer cell lines in vitro, as well as prostate tumor xenograft, and wild-type mouse prostate tissue in vivo. Ad transduction efficiency was determined by EGFP fluorescence using microscopy and flow cytometry. Cell type-specific transduction was examined by immunofluorescence staining of cell markers. Our data showed that Ad efficiently transduced human and mouse prostate cancer cells in vitro in a dose dependent manner. Following intratumoral and intraprostate injection, Ad could efficiently transduce prostate tumor xenograft and the major prostatic cell types in vivo, respectively. Our findings suggest that Ad can efficiently transduce prostate tumor cells in vitro as well as xenograft and normal prostate tissue in vivo, and further indicate that Ad could be a potentially powerful toolbox for future gene therapy of prostate diseases. © 2017 Wiley Periodicals, Inc.

Canine prostate models in preclinical studies of minimally invasive interventions: part II, benign prostatic hyperplasia models

PubMed Central

Báez-Díaz, Claudia; Sánchez-Margallo, Francisco Miguel

2017-01-01

Canine prostate is widely used as animal model in the preclinical evaluation of emerging therapeutic interventions. Spontaneous benign prostatic hyperplasia (BPH) is common in adult intact male dogs with two distinct pathological types: glandular and complex form of prostatic hyperplasia. The complex form of prostatic hyperplasia, usually occurring in older dogs, represents an ideal model because of its unique pathologic feature, including not only glandular hyperplasia but also an increase in prostate stromal components. The limited commercial availability of adult dogs with spontaneous BPH motivates experimentally induced BPH in young dogs. Hormone-induced canine BPH model has been well established with various hormonal treatment regimens and administration approaches. The goal of this review is to provide the veterinary background in spontaneous BPH in dogs, summarize the techniques in hormonal induction of canine BPH, and highlight the pathological and clinical limitations of the canine models that may lead to distinct therapeutic responses compared to clinical trials in humans. PMID:28725598

Health-related quality of life, satisfaction, and economic outcome measures in studies of prostate cancer screening and treatment, 1990-2000.

PubMed

McNaughton-Collins, Mary; Walker-Corkery, Elizabeth; Barry, Michael J

2004-01-01

Prostate cancer outcomes research incorporates a broad spectrum of endpoints, from clinical or intermediate endpoints, such as tumor shrinkage or patient compliance, to final endpoints, such as survival or disease-free survival. Three types of nontraditional endpoints that are of growing interest-health-related quality of life (QOL), satisfaction with care, and economic cost impact-hold the promise of improving our ability to understand the full burden of prostate cancer screening and treatment. In this article we review the last decade's published literature regarding the health-related QOL, satisfaction, and economic outcomes of prostate cancer screening and treatment to determine the "state of the science" of outcomes measurement. The focus is the enumeration of the types of outcome measurement used in the studies not the determination of the results of the studies. Studies were identified by searching Medline (1990-2000). Articles were included if they presented original data on any patient-centered outcome (including costs or survival alone) for men screened and treated for prostate cancer. Review papers were excluded unless they were quantitative syntheses of the results of other primary studies. Economic and decision analytic papers were included if they presented information on outcomes of real or hypothetical patient cohorts. Each retrieved article was reviewed by one of the authors. Included papers were assigned one primary, mutually exclusive study design. For the "primary data" studies, information was abstracted on care setting, dates of the study, sample size, racial distribution, age, tumor differentiation, tumor stage, survival, statistical power, and types of outcomes measures (QOL-generic, QOL-cancer specific, QOL-prostate cancer specific, satisfaction, costs, utilities, and other). For the "economic and decision analytic" papers, information was abstracted on stage of disease, age range, outcomes, costs, and whether utilities were measured. Of the 198 included papers, there were 161 primary data papers categorized as follows: randomized trial (n = 28), nonrandomized trial (n = 13), prospective or retrospective cohort study (n = 55), case-control study (n = 0), cross-sectional study (n = 63), and meta-analysis (n = 2). The remaining 37 papers were economic and decision analytic papers. Among the 149 primary data papers that contained patient outcome data, there were 42 standard instruments used, accounting for 44% (179 of 410) of the measures overall. Almost three-quarters (71%) of papers included one, two, or three outcomes measures of all types (standard and nonstandard); three papers included seven outcomes measures, and one paper included nine. Over the 11-year time period, there was a nonstatistically significant trend toward more frequent use of standardized QOL instruments and a statistically significant trend toward increased reporting of race (P = .003). Standardization of measurement of health-related QOL, satisfaction with care, and economic cost effect among men screened and treated for prostate cancer is needed. A core set of similar questions, both generic and disease-specific, should ideally be asked in every study, although investigators should be encouraged to include additional question sets as appropriate to individual studies to get a more complete picture of how patients screened and treated for this condition are doing over time.

Did You Know? Video Series - SEER Cancer Statistics

Cancer.gov

Videos that explain cancer statistics. Choose from topics including survival, statistics overview, survivorship, disparities, and specific cancer types including breast, lung, colorectal, prostate, melanoma of the skin, and others.

Current status of 5α-reductase inhibitors in prostate disease management.

PubMed

Kang, Dong Il; Chung, Jae Il

2013-04-01

The key enzyme in the androgen synthesis and androgen receptor pathways is 5α-reductase (5-AR), which occurs as three isoenzymes. Types I and II 5-ARs the most important clinically, and two different 5-AR inhibitors (5-ARIs), finasteride and dutasteride, have been developed. Several urology associations have recommended and upgraded the use of 5-ARIs for an enlarged prostate with lower urinary tract symptoms. In the Prostate Cancer Prevention Trial and the Reduction by Dutasteride of Prostate Cancer Events Trial, 5-ARIs reduced the incidence of low-grade prostate cancer. However, despite the documented reductions in the overall incidence of prostate cancer, 5-ARIs are at the center of a dispute. The American Society of Clinical Oncology (ASCO) and the American Urology Association (AUA) presented clinical guidelines for the use of 5-ARIs for chemoprevention of prostate cancer in 2008. However, ASCO/AUA has eliminated these from the main "Clinical Guidelines" in 2012, because the U.S. Food and Drug Administration denied a supplemental New Drug Application for the use of dutasteride for prostate cancer chemoprevention. The 5-ARIs can also be used to manage hemospermia and prostatic hematuria, and to prevent intraoperative bleeding, although there is insufficient evidence for a standard strategy. This review summarizes the current use of 5-ARIs for prostate disease, including benign prostate hyperplasia, prostate cancer, prostate-related bleeding, and hemospermia.

Differential receptor dependencies: expression and significance of muscarinic M1 receptors in the biology of prostate cancer.

PubMed

Mannan Baig, Abdul; Khan, Naveed A; Effendi, Vardah; Rana, Zohaib; Ahmad, H R; Abbas, Farhat

2017-01-01

Recent reports on acetylcholine muscarinic receptor subtype 3 (CHRM3) have shown its growth-promoting role in prostate cancer. Additional studies report the proliferative effect of the cholinergic agonist carbachol on prostate cancer by its agonistic action on CHRM3. This study shows that the type 1 acetylcholine muscarinic receptor (CHRM1) contributes toward the proliferation and growth of prostate cancer. We used growth and cytotoxic assays, the prostate cancer microarray database and CHRM downstream pathways' homology of CHRM subtypes to uncover multiple signals leading to the growth of prostate cancer. Growth assays showed that pilocarpine stimulates the proliferation of prostate cancer. Moreover, it shows that carbachol exerts an additional agonistic action on nicotinic cholinergic receptor of prostate cancer cells that can be blocked by tubocurarine. With the use of selective CHRM1 antagonists such as pirenzepine and dicyclomine, a considerable inhibition of proliferation of prostate cancer cell lines was observed in dose ranging from 15-60 µg/ml of dicyclomine. The microarray database of prostate cancer shows a dominant expression of CHRM1 in prostate cancer compared with other cholinergic subtypes. The bioinformatics of prostate cancer and CHRM pathways show that the downstream signalling include PIP3-AKT-CaM-mediated growth in LNCaP and PC3 cells. Our study suggests that antagonism of CHRM1 may be a potential therapeutic target against prostate cancer.

Molecular Validation of PACE4 as a Target in Prostate Cancer12

PubMed Central

D'Anjou, François; Routhier, Sophie; Perreault, Jean-Pierre; Latil, Alain; Bonnel, David; Fournier, Isabelle; Salzet, Michel; Day, Robert

2011-01-01

Prostate cancer remains the single most prevalent cancer in men. Standard therapies are still limited and include androgen ablation that initially causes tumor regression. However, tumor cells eventually relapse and develop into a hormone-refractory prostate cancer. One of the current challenges in this disease is to define new therapeutic targets, which have been virtually unchanged in the past 30 years. Recent studies have suggested that the family of enzymes known as the proprotein convertases (PCs) is involved in various types of cancers and their progression. The present study examined PC expression in prostate cancer and validates one PC, namely PACE4, as a target. The evidence includes the observed high expression of PACE4 in all different clinical stages of human prostate tumor tissues. Gene silencing studies targeting PACE4 in the DU145 prostate cancer cell line produced cells (cell line 4-2) with slower proliferation rates, reduced clonogenic activity, and inability to grow as xenografts in nude mice. Gene expression and proteomic profiling of the 4-2 cell line reveals an increased expression of known cancer-related genes (e.g., GJA1, CD44, IGFBP6) that are downregulated in prostate cancer. Similarly, cancer genes whose expression is decreased in the 4-2 cell line were upregulated in prostate cancer (e.g., MUC1, IL6). The direct role of PACE4 in prostate cancer is most likely through the upregulated processing of growth factors or through the aberrant processing of growth factors leading to sustained cancer progression, suggesting that PACE4 holds a central role in prostate cancer. PMID:21633671

The identification of incident cancers in UK primary care databases: a systematic review.

PubMed

Rañopa, Michael; Douglas, Ian; van Staa, Tjeerd; Smeeth, Liam; Klungel, Olaf; Reynolds, Robert; Bhaskaran, Krishnan

2015-01-01

UK primary care databases are frequently used in observational studies with cancer outcomes. We aimed to systematically review methods used by such studies to identify and validate incident cancers of the breast, colorectum, and prostate. Medline and Embase (1980-2013) were searched for UK primary care database studies with incident breast, colorectal, or prostate cancer outcomes. Data on the methods used for case ascertainment were extracted and summarised. Questionnaires were sent to corresponding authors to obtain details about case ascertainment. Eighty-four studies of breast (n = 51), colorectal (n = 54), and prostate cancer (n = 31) were identified; 30 examined >1 cancer type. Among the 84 studies, 57 defined cancers using only diagnosis codes, while 27 required further evidence such as chemotherapy. Few studies described methods used to create cancer code lists (n = 5); or made lists available directly (n = 5). Twenty-eight code lists were received on request from study authors. All included malignant neoplasm diagnosis codes, but there was considerable variation in the specific codes included which was not explained by coding dictionary changes. Code lists also varied in terms of other types of codes included, such as in-situ, cancer morphology, history of cancer, and secondary/suspected/borderline cancer codes. In UK primary care database studies, methods for identifying breast, colorectal, and prostate cancers were often unclear. Code lists were often unavailable, and where provided, we observed variation in the individual codes and types of codes included. Clearer reporting of methods and publication of code lists would improve transparency and reproducibility of studies. Copyright © 2014 John Wiley & Sons, Ltd.

Precision medicine for advanced prostate cancer

PubMed Central

Mullane, Stephanie A.; Van Allen, Eliezer M.

2016-01-01

Purpose of review Precision cancer medicine, the use of genomic profiling of patient tumors at the point-of-care to inform treatment decisions, is rapidly changing treatment strategies across cancer types. Precision medicine for advanced prostate cancer may identify new treatment strategies and change clinical practice. In this review, we discuss the potential and challenges of precision medicine in advanced prostate cancer. Recent findings Although primary prostate cancers do not harbor highly recurrent targetable genomic alterations, recent reports on the genomics of metastatic castration-resistant prostate cancer has shown multiple targetable alterations in castration-resistant prostate cancer metastatic biopsies. Therapeutic implications include targeting prevalent DNA repair pathway alterations with PARP-1 inhibition in genomically defined subsets of patients, among other genomically stratified targets. In addition, multiple recent efforts have demonstrated the promise of liquid tumor profiling (e.g., profiling circulating tumor cells or cell-free tumor DNA) and highlighted the necessary steps to scale these approaches in prostate cancer. Summary Although still in the initial phase of precision medicine for prostate cancer, there is extraordinary potential for clinical impact. Efforts to overcome current scientific and clinical barriers will enable widespread use of precision medicine approaches for advanced prostate cancer patients. PMID:26909474

Precision medicine for advanced prostate cancer.

PubMed

Mullane, Stephanie A; Van Allen, Eliezer M

2016-05-01

Precision cancer medicine, the use of genomic profiling of patient tumors at the point-of-care to inform treatment decisions, is rapidly changing treatment strategies across cancer types. Precision medicine for advanced prostate cancer may identify new treatment strategies and change clinical practice. In this review, we discuss the potential and challenges of precision medicine in advanced prostate cancer. Although primary prostate cancers do not harbor highly recurrent targetable genomic alterations, recent reports on the genomics of metastatic castration-resistant prostate cancer has shown multiple targetable alterations in castration-resistant prostate cancer metastatic biopsies. Therapeutic implications include targeting prevalent DNA repair pathway alterations with PARP-1 inhibition in genomically defined subsets of patients, among other genomically stratified targets. In addition, multiple recent efforts have demonstrated the promise of liquid tumor profiling (e.g., profiling circulating tumor cells or cell-free tumor DNA) and highlighted the necessary steps to scale these approaches in prostate cancer. Although still in the initial phase of precision medicine for prostate cancer, there is extraordinary potential for clinical impact. Efforts to overcome current scientific and clinical barriers will enable widespread use of precision medicine approaches for advanced prostate cancer patients.

PTEN Loss and Reactive Microenvironments in Prostate Cancer Progression

DTIC Science & Technology

2011-07-01

obesity, and dyslipidemia in prostate disease, thin layer chromatography was performed on the mPrEPPARgKO and rescue cells to determine the fatty acid...review retrospective clinical studies that have drawn associations between BPH/LUTS and type II diabetes, inflammation and dyslipidemia . PPARg signaling...profile of findings including impaired glucose metabolism, obesity, altered fat dis- tribution, hypertension, dyslipidemia , markers of systemic inflam

Biothermal modeling of transurethral ultrasound applicators for MR-guided prostate thermal therapy (Invited Paper)

NASA Astrophysics Data System (ADS)

Ross, Anthony B.; Diederich, Chris J.; Nau, William H.; Tyreus, Per D.; Gill, Harcharan; Bouley, Donna; Butts, R. K.; Rieke, Viola; Daniel, Bruce; Sommer, Graham

2005-04-01

Thermal ablation is a minimally-invasive treatment option for benign prostatic hyperplasia (BPH) and localized prostate cancer. Accurate spatial control of thermal dose delivery is paramount to improving thermal therapy efficacy and avoiding post-treatment complications. We have recently developed three types of transurethral ultrasound applicators, each with different degrees of heating selectivity. These applicators have been evaluated in vivo in coordination with magnetic resonance temperature imaging, and demonstrated to accurately ablate specific regions of the canine prostate. A finite difference biothermal model of the three types of transurethral ultrasound applicators (sectored tubular, planar, and curvilinear transducer sections) was developed and used to further study the performance and heating capabilities of each these devices. The biothermal model is based on the Pennes bioheat equation. The acoustic power deposition pattern corresponding to each applicator type was calculated using the rectangular radiator approximation to the Raleigh Sommerfield diffraction integral. In this study, temperature and thermal dose profiles were calculated for different treatment schemes and target volumes, including single shot and angular scanning procedures. This study also demonstrated the ability of the applicators to conform the cytotoxic thermal dose distribution to a predefined target area. Simulated thermal profiles corresponded well with MR temperature images from previous in vivo experiments. Biothermal simulations presented in this study reinforce the potential of improved efficacy of transurethral ultrasound thermal therapy of prostatic disease.

Desquamation takes center stage at the origin of proliferative inflammatory atrophy, epithelial-mesenchymal transition, and stromal growth in benign prostate hyperplasia.

PubMed

Ferrucci, Danilo; Biancardi, Manoel F; Nishan, Umar; Rosa-Ribeiro, Rafaela; Carvalho, Hernandes F

2017-11-01

In this commentary, we propose a relationship between desquamation, initially described as the collective detachment and deletion of epithelial cell in the prostate gland after castration, and proliferative inflammatory atrophy (PIA) and stromal growth in benign prostate hyperplasia (BPH). First, in response to diverse stimuli, including inflammatory mediators, epithelial cells desquamate and leave a large surface of the luminal side of the basement membrane (BM) exposed. Basal cells are activated into intermediate-type cells, which change morphology to cover and remodel the exposed BM (simple atrophy) to a new physiological demand (such as in the hypoandrogen environment, simulated by surgical and/or chemical castration) and/or to support re-epithelialization (under normal androgen levels). In the presence of inflammation (that might be the cause of desquamation), the intermediate-type cells proliferate and characterize PIA. Second, in other circumstances, desquamation is an early step of epithelial-to-mesenchymal transition (EMT), which contributes to stromal growth, as suggested by some experimental models of BPH. The proposed associations correlate unexplored cell behaviors and reveal the remarkable plasticity of the prostate epithelium that might be at the origin of prostate diseases. © 2017 International Federation for Cell Biology.

Metformin Has a Positive Therapeutic Effect on Prostate Cancer in Diabetes Mellitus 2 Patients

PubMed Central

Chong, R. William; Vasudevan, Vijaya; Zuber, Jeffrey; Solomon, Solomon S.

2016-01-01

Objective Prostate cancer and type 2 diabetes mellitus are both common diseases found in the elderly male population. The diabetic drug, metformin, has been shown to have anti-neoplastic properties and demonstrated better treatment outcomes when used as adjuvant therapy in breast cancer patients. The hormonally-sensitive cancer analogous to breast in men is prostate. We investigated improved survival, lower risks of recurrences, and lower, more stable levels of prostate specific antigen (PSA) in DM2 patients with prostate cancer on metformin. Methods Prostate cancer patients with type 2 diabetes that remained on metformin were compared to controls not on metformin matched by age, weight, race, and Gleason score cancer staging. The endpoints of our study included final PSA values, number of recurrences, metastases and number living for each group. Results There were significantly fewer deaths (23% vs 10%), fewer recurrences (15% vs 8%), and fewer metastases (5% vs 0%), and fewer secondary cancers (17% vs 6%) in the metformin group (p<0.004). The final PSA value was lower in the metformin-treated group with a result approaching significance (p=0.067). The primary treatments for prostate cancer (i.e. surgery, radiation, androgen depletion) were found to be comparable in both groups. Conclusions Our retrospective study shows that adjuvant metformin therapy leads to a better prognosis in prostate cancer. Not only are PSA levels controlled for several years, but there are significantly fewer cancer recurrences in metformin treated patients. Overall, these results are promising and should be followed up with a prospective study to assess long-term survival. PMID:27079349

[Longjintonglin Capsules for type IIIA prostatitis accompanied by abnormal semen liquefaction: A clinical observation].

PubMed

Cai, Hong-cai; Wan, Chang-chun; Geng, Qiang; Liu, Wei; Zhang, Guo-wei; Shang, Xue-jun; Huang, Yu-feng

2016-01-01

To evaluate the therapeutic effect of Longjintonglin Capsules on type IIIA prostatitis accompanied by abnormal semen liquefaction. We selected 140 patients with type IIIA prostatitis accompanied by abnormal semen liquefaction according to the diagnostic standards of the American Institutes of Health (NIH) and treated them with Longjintonglin Capsules orally 3 capsules once tid for 12 weeks. We obtained the NIH Chronic Prostatitis Symptom Indexes (NIH-CPSI), traditional Chinese medicine (TCM) syndrome scores, leukocyte count in the expressed prostatic secretion (EPS), semen liquefaction time, and the results of semen analysis and compared these indicators before and after the treatment. Of the 140 cases, 132 were included in this study, excluding 8 due to their incomplete case histories. Before and after 4, 8 and 12 weeks of medication, the total NIH-CPSI scores were 24.52 ± 5.43, 21.28 ± 4.85, 18.01 ± 4.28, and 14.49 ± 3.65 (P < 0.01), the TCM syndrome scores were 35.63 ± 6.07, 26.66 ± 5.03, 17.37 ± 4.18, and 11.11 ± 3.96 (P < 0.01), and the leukocyte counts (/HP) were 27.50 ± 7.01, 22.38 ± 5.22, 16:76 ± 4.10, and 11.40 ± 4.74 (P < 0.01), respectively. After 12 weeks of treatment, 31 of the patients with type IIIA prostatitis were cured and another 72 well responded, with an overall response rate of 78.0%. Of those with abnormal semen liquefaction, 61 were cured, 39 well responded, and 32 failed to respond, with an overall effectiveness rate of 75.8%. Semen analysis showed significantly increased percentage of progressively motile sperm after 4, 8 and 12 weeks of medication as compared with the baseline (P < 0.01). No abnormal liver or renal function or other adverse reactions were observed during the treatment. Longjintonglin Capsules, with its advantages of safety, effectiveness and no obvious adverse effects, deserve to be recommended for the treatment of type IIIA prostatitis accompanied by abnormal semen liquefaction.

Incidental Detection of Type B2 Thymoma on 68Ga-Labeled Prostate-Specific Membrane Antigen PET/CT Imaging.

PubMed

Krishnaraju, Venkata Subramanian; Basher, Rajender Kumar; Singh, Harmandeep; Singh, Shrawan Kumar; Bal, Amanjit; Mittal, Bhagwant Rai

2018-05-01

Ga-labeled prostate-specific membrane antigen is a novel radiotracer for imaging of prostate cancer. We report a hormonally treated patient with prostate carcinoma, presenting with lower urinary tract symptoms and rising prostate-specific antigen levels, who underwent Ga-labeled prostate-specific membrane antigen PET/CT for suspected recurrence. No tracer avid lesion was noted in the prostate gland and locoregional area. However, intense tracer avid heterogeneously enhancing soft tissue lesion with cystic areas and coarse calcifications was seen in the anterior mediastinum. PET/CT-guided biopsy from the mediastenal lesion revealed type B2 thymoma.

Novel Nine-Exon AR Transcripts (Exon 1/Exon 1b/Exons 2–8) in Normal and Cancerous Breast and Prostate Cells

PubMed Central

Hu, Dong Gui; McKinnon, Ross A.; Hulin, Julie-Ann; Mackenzie, Peter I.; Meech, Robyn

2016-01-01

Nearly 20 different transcripts of the human androgen receptor (AR) are reported with two currently listed as Refseq isoforms in the NCBI database. Isoform 1 encodes wild-type AR (type 1 AR) and isoform 2 encodes the variant AR45 (type 2 AR). Both variants contain eight exons: they share common exons 2–8 but differ in exon 1 with the canonical exon 1 in isoform 1 and the variant exon 1b in isoform 2. Splicing of exon 1 or exon 1b is reported to be mutually exclusive. In this study, we identified a novel exon 1b (1b/TAG) that contains an additional TAG trinucleotide upstream of exon 1b. Moreover, we identified AR transcripts in both normal and cancerous breast and prostate cells that contained either exon 1b or 1b/TAG spliced between the canonical exon 1 and exon 2, generating nine-exon AR transcripts that we have named isoforms 3a and 3b. The proteins encoded by these new AR variants could regulate androgen-responsive reporters in breast and prostate cancer cells under androgen-depleted conditions. Analysis of type 3 AR-GFP fusion proteins showed partial nuclear localization in PC3 cells under androgen-depleted conditions, supporting androgen-independent activation of the AR. Type 3 AR proteins inhibited androgen-induced growth of LNCaP cells. Microarray analysis identified a small set of type 3a AR target genes in LNCaP cells, including genes known to modulate growth and proliferation of prostate cancer (PCGEM1, PEG3, EPHA3, and EFNB2) or other types of human cancers (TOX3, ST8SIA4, and SLITRK3), and genes that are diagnostic/prognostic biomarkers of prostate cancer (GRINA3, and BCHE). PMID:28035996

Notch signaling dynamics in the adult healthy prostate and in prostatic tumor development.

PubMed

Pedrosa, Ana-Rita; Graça, José L; Carvalho, Sandra; Peleteiro, Maria C; Duarte, António; Trindade, Alexandre

2016-01-01

The Notch signaling pathway has been implicated in prostate development, maintenance and tumorigenesis by its key role in cell-fate determination, differentiation and proliferation. Therefore, we proposed to analyze Notch family members transcription and expression, including ligands (Dll1, 3, 4 and Jagged1 and 2), receptors (Notch1-4) and effectors (Hes1, 2, 5 and Hey1, 2, L), in both normal and tumor bearing mouse prostates to better understand the dynamics of Notch signaling in prostate tumorigenesis. Wild type mice and transgenic adenocarcinoma of the mouse prostate model (TRAMP) mice were sacrificed at 18, 24 or 30 weeks of age and the prostates collected and processed for either whole prostate or prostate cell specific populations mRNA analysis and for protein expression analysis by immunohistochemistry and immunofluorescence. We observed that Dll1 and Dll4 are expressed in the luminal compartment of the mouse healthy prostate, whereas Jagged2 expression is restricted to the basal and stromal compartment. Additionally, Notch2 and Notch4 are normally expressed in the prostate luminal compartment while Notch2 and Notch3 are also expressed in the stromal layer of the healthy prostate. As prostate tumor development takes place, there is up-regulation of Notch components. Particularly, the prostate tumor lesions have increased expression of Jagged1 and 2, of Notch3 and of Hey1. We have also detected the presence of activated Notch3 in prostatic tumors that co-express Jagged1 and ultimately the Hey1 effector. Taken together our results point out the Notch axis Jagged1-2/Notch3/Hey1 to be important for prostate tumor development and worthy of additional functional studies and validation in human clinical disease. © 2015 Wiley Periodicals, Inc.

The economic effect of using magnetic resonance imaging and magnetic resonance ultrasound fusion biopsy for prostate cancer diagnosis.

PubMed

Hutchinson, Ryan C; Costa, Daniel N; Lotan, Yair

2016-07-01

Prostate magnetic resonance imaging (MRI) is a maturing imaging modality that has been used to improve detection and staging of prostate cancer. The goal of this review is to evaluate the economic effect of the use of MRI and MRI fusion in the diagnosis of prostate cancer. A literature review was used to identify articles regarding efficacy and cost of MRI and MRI-guided biopsies. There are currently a limited number of studies evaluating cost of incorporating MRI into clinical practice. These studies are primarily models projecting cost estimates based on meta-analyses of the literature. There is considerable variance in the effectiveness of MRI-guided biopsies, both cognitive and fusion, based on user experience, type of MRI (3T vs. 1.5T), use of endorectal coil and type of scoring system for abnormalities such that there is still potential for improvement in accuracy. There is also variability in assumed costs of incorporating MRI into clinical practice. The addition of MRI to the diagnostic algorithm for prostate cancer has caused a shift in how we understand the disease and in what tumors are found on initial and repeat biopsies. Further risk stratification may allow more men to pursue noncurative therapy, which in and of itself is cost-effective in properly selected men. As prostate cancer care comes under increasing scrutiny on a national level, there is pressure on providers to be more accurate in their diagnoses. This in turn can lead to additional testing including Multiparametric MRI, which adds upfront cost. Whether the additional cost of prostate MRI is warranted in detection of prostate cancer is an area of intense research. Copyright © 2016 Elsevier Inc. All rights reserved.

Role of the ARF Tumor Suppressor in Prostate Cancer

DTIC Science & Technology

2005-10-01

found that ARF expression is absence from highly proliferative prostate adenocarcinomas and this correlates with the increased expression of the p53...prostate is unknown. The preliminary data for my orginal proposal indicated that prostate adenocarcinomas typically maintain wild type p53 (97%), but...independent mechanisms to regulate prostate cell proliferation. Table 1. Protein Expression in Prostate Adenocarcinomas Human prostate tissue samples

Prostate Diseases

MedlinePlus

... Home › Aging & Health A to Z › Prostate Diseases Font size A A A Print Share Glossary Basic ... body. Approximately 3 million American men have some type of prostate disease. The most common prostate diseases ...

Inflammation on Prostate Needle Biopsy is Associated with Lower Prostate Cancer Risk: A Meta-Analysis.

PubMed

Vasavada, Shaleen R; Dobbs, Ryan W; Kajdacsy-Balla, André A; Abern, Michael R; Moreira, Daniel M

2018-05-01

We performed a comprehensive literature review and meta-analysis to evaluate the association of inflammation on prostate needle biopsies and prostate cancer risk. We searched Embase®, PubMed® and Web of Science™ from January 1, 1990 to October 1, 2016 for abstracts containing the key words prostate cancer, inflammation and biopsy. Study inclusion criteria were original research, adult human subjects, cohort or case-control study design, histological inflammation on prostate needle biopsy and prostate cancer on histology. Two independent teams reviewed abstracts and extracted data from the selected manuscripts. Combined ORs and 95% CIs of any, acute and chronic inflammation were calculated using the random effects method. Of the 1,030 retrieved abstracts 46 underwent full text review and 25 were included in the final analysis, comprising a total of 20,585 subjects and 6,641 patients with prostate cancer. There was significant heterogeneity among studies (I 2 = 84.4%, p <0.001). The presence of any inflammation was significantly associated with a lower prostate cancer risk in 25 studies (OR 0.455, 95% CI 0.337-0.573). There was no evidence of publication bias (p >0.05). When subanalyzed by inflammation type, acute inflammation in 4 studies and chronic inflammation in 15 were each associated with a lower prostate cancer risk (OR 0.681, 95% CI 0.450-0.913 and OR 0.499, 95% CI 0.334-0.665, respectively). In a meta-analysis of 25 studies inflammation on prostate needle biopsy was associated with a lower prostate cancer risk. Clinically the presence of inflammation on prostate needle biopsy may lower the risk of a subsequent prostate cancer diagnosis. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Recurrent Prostate Infection: What Are the Treatment Options?

MedlinePlus

... recurring prostate infection, also known as chronic bacterial prostatitis, is typically treated with antibiotics. This type of ... Erik P. Castle, M.D. Pontari M. Chronic prostatitis/chronic pelvic pain syndrome. https://www.uptodate.com/ ...

Current status of cryotherapy for prostate and kidney cancer.

PubMed

Cho, Seok; Kang, Seok Ho

2014-12-01

In terms of treating diseases, minimally invasive treatment has become a key element in reducing perioperative complications. Among the various minimally invasive treatments, cryotherapy is often used in urology to treat various types of cancers, especially prostate cancer and renal cancer. In prostate cancer, the increased incidence of low-risk, localized prostate cancer has made minimally invasive treatment modalities an attractive option. Focal cryotherapy for localized unilateral disease offers the added benefit of minimal morbidities. In renal cancer, owing to the increasing utilization of cross-sectional imaging, nearly 70% of newly detected renal masses are stage T1a, making them more susceptible to minimally invasive nephron-sparing therapies including laparoscopic and robotic partial nephrectomy and ablative therapies. This article reviews the various outcomes of cryotherapy compared with other treatments and the possible uses of cryotherapy in surgery.

Current Status of Cryotherapy for Prostate and Kidney Cancer

PubMed Central

Cho, Seok

2014-01-01

In terms of treating diseases, minimally invasive treatment has become a key element in reducing perioperative complications. Among the various minimally invasive treatments, cryotherapy is often used in urology to treat various types of cancers, especially prostate cancer and renal cancer. In prostate cancer, the increased incidence of low-risk, localized prostate cancer has made minimally invasive treatment modalities an attractive option. Focal cryotherapy for localized unilateral disease offers the added benefit of minimal morbidities. In renal cancer, owing to the increasing utilization of cross-sectional imaging, nearly 70% of newly detected renal masses are stage T1a, making them more susceptible to minimally invasive nephron-sparing therapies including laparoscopic and robotic partial nephrectomy and ablative therapies. This article reviews the various outcomes of cryotherapy compared with other treatments and the possible uses of cryotherapy in surgery. PMID:25512811

Management of severe urethral complications of prostate cancer therapy.

PubMed

Elliott, Sean P; McAninch, Jack W; Chi, Thomas; Doyle, Sean M; Master, Viraj A

2006-12-01

We present our management of urethral stenosis and rectourinary fistula resulting from prostate cancer therapy. We concentrated on cases refractory to minimally invasive treatment, such as dilation, urethrotomy, and urinary and/or fecal diversion. In our prospectively collected urethral reconstruction database we identified patients who underwent reconstruction of urethral stenosis or rectourinary fistula who also received prior treatment for prostate cancer. We documented demographics, prostate cancer pretreatment characteristics, prostate cancer therapy type, urethral reconstruction type and success. A total of 48 patients met the inclusion criteria, including 16 with rectourinary fistula and 32 with urethral stenosis. Urethral complications followed prior radical prostatectomy, brachytherapy, external beam radiotherapy, cryotherapy, thermal ablation and any combination of these procedures. Stenosis repair was successful in 23 of 32 cases (73%) and it differed little between anterior and posterior urethral stenosis. Repair was accomplished by anastomotic urethroplasty in 19 cases, flap urethroplasty in 2, perineal urethrostomy in 2 and a urethral stent in 9. Prior external beam radiotherapy was a risk factor for urethral reconstruction failure. Fistula repair was successful in 14 of 15 patients (93%), excluding 1 who died postoperatively. The complexity of fistula management was dictated by fistula size and the presence or absence of coincident urethral stenosis. Urethral stenosis or rectourethral fistula following prostate cancer therapy can be managed by urethral reconstruction, such that normal voiding via the urethra is maintained, rather than abandoning the urethral outlet and performing heterotopic diversion. This can be accomplished with an acceptable rate of failure, given the complexity of the cases.

No Effect of Music on Anxiety and Pain During Transrectal Prostate Biopsies: A Randomized Trial.

PubMed

Packiam, Vignesh T; Nottingham, Charles U; Cohen, Andrew J; Eggener, Scott E; Gerber, Glenn S

2018-07-01

To investigate the effect of ambient music on anxiety and pain in men undergoing prostate biopsies. Between September 2015 and June 2016, men undergoing office transrectal prostate biopsy at our institution were randomly assigned to music (n = 85) or control (n = 97) groups. We examined clinical characteristics, pathologic variables, and baseline anxiety using the Trait Instrument of State-Trait Anxiety Inventory. Primary outcomes included anxiety assessed by State Instrument of STAI (STAI-S) and pain using a visual analog scale. There were no significant differences in baseline characteristics between the music and control groups, including median age, prostate-specific antigen, use of magnetic resonance imaging-guided biopsies, or Trait Instrument of State-Trait Anxiety Inventory. The majority (93%) of patients indicated they desired music in their prebiopsy survey. There were no significant differences in STAI-S (33.7 ± 8.9 vs 34.4 ± 9.9, P = .6), pain score (2.3 ± 2.1 vs 2.0 ± 2.1, P = .3), or vital signs between the music and control groups, respectively. There were also no differences in STAI-S, visual analog scale, or vital signs between groups when stratified by age, prostate-specific antigen, or number of previous biopsies. Men who received music were more likely to request music for future prostate biopsy, compared to men who did not (93% vs 83%, P = .07, respectively). This randomized study showed no difference in anxiety or pain scores for patients who had ambient music during transrectal prostate biopsy. Future studies are needed to discern the influence of details including method of music delivery, music type, and utilization of adjunct relaxation tools. Copyright © 2018 Elsevier Inc. All rights reserved.

Urethroplasty After Radiation Therapy for Prostate Cancer

PubMed Central

Glass, Allison S.; McAninch, Jack W.; Zaid, Uwais B.; Cinman, Nadya M.; Breyer, Benjamin N.

2013-01-01

OBJECTIVE To report urethroplasty outcomes in men who developed urethral stricture after undergoing radiation therapy for prostate cancer. METHODS Our urethroplasty database was reviewed for cases of urethral stricture after radiation therapy for prostate cancer between June 2004 and May 2010. Patient demographics, prostate cancer therapy type, stricture length and location, and type of urethroplasty were obtained. All patients received clinical evaluation, including imaging studies post procedure. Treatment success was defined as no need for repeat surgical intervention. RESULTS Twenty-nine patients underwent urethroplasty for radiation-induced stricture. Previous radiation therapy included external beam radiotherapy (EBRT), radical prostatectomy (RP)/EBRT, EBRT/brachytherapy (BT) and BT alone in 11 (38%), 7 (24%), 7 (24%), and 4 (14%) patients, respectively. Mean age was 69 (±6.9) years. Mean stricture length was 2.6 (±1.6) cm. Anastomotic urethroplasty was performed in 76% patients, buccal mucosal graft in 17%, and perineal flap repair in 7%. Stricture was localized to bulbar urethra in 12 (41%), membranous in 12 (41%), vesicourethra in 3 (10%), and pan-urethral in 2 (7%) patients. Overall success rate was 90%. Median follow-up was 40 months (range 12-83). Time to recurrence ranged from 6-16 months. CONCLUSION Multiple forms of urethroplasty appear to be viable options in treating radiation-induced urethral stricture. Future studies are needed to examine the durability of repairs. PMID:22521189

Pairing Physician Education With Patient Activation to Improve Shared Decisions in Prostate Cancer Screening: A Cluster Randomized Controlled Trial

PubMed Central

Wilkes, Michael S.; Day, Frank C.; Srinivasan, Malathi; Griffin, Erin; Tancredi, Daniel J.; Rainwater, Julie A.; Kravitz, Richard L.; Bell, Douglas S.; Hoffman, Jerome R.

2013-01-01

BACKGROUND Most expert groups recommend shared decision making for prostate cancer screening. Most primary care physicians, however, routinely order a prostate-specific antigen (PSA) test with little or no discussion about whether they believe the potential benefits justify the risk of harm. We sought to assess whether educating primary care physicians and activating their patients to ask about prostate cancer screening had a synergistic effect on shared decision making, rates and types of discussions about prostate cancer screening, and the physician’s final recommendations. METHODS Our study was a cluster randomized controlled trial among primary care physicians and their patients, comparing usual education (control), with physician education alone (MD-Ed), and with physician education and patient activation (MD-Ed+A). Participants included 120 physicians in 5 group practices, and 712 male patients aged 50 to 75 years. The interventions comprised a Web-based educational program for all intervention physicians and MD-Ed+A patients compared with usual education (brochures from the Centers for Disease Control and Prevention). The primary outcome measure was patients’ reported postvisit shared decision making regarding prostate cancer screening; secondary measures included unannounced standardized patients’ reported shared decision making and the physician’s recommendation for prostate cancer screening. RESULTS Patients’ ratings of shared decision making were moderate and did not differ between groups. MD-Ed+A patients reported that physicians had higher prostate cancer screening discussion rates (MD-Ed+A = 65%, MD-Ed = 41%, control=38%; P <.01). Standardized patients reported that physicians seeing MD-Ed+A patients were more neutral during prostate cancer screening recommendations (MD-Ed+A=50%, MD-Ed=33%, control=15%; P <.05). Of the male patients, 80% had had previous PSA tests. CONCLUSIONS Although activating physicians and patients did not lead to significant changes in all aspects of physician attitudes and behaviors that we studied, interventions that involved physicians did have a large effect on their attitudes toward screening and in the discussions they had with patients, including their being more likely than control physicians to engage in prostate cancer screening discussions and more likely to be neutral in their final recommendations. PMID:23835818

Fluorescence in situ hybridization evaluation of chromosome deletion patterns in prostate cancer.

PubMed

Huang, S F; Xiao, S; Renshaw, A A; Loughlin, K R; Hudson, T J; Fletcher, J A

1996-11-01

Various nonrandom chromosomal aberrations have been identified in prostate carcinoma. These aberrations include deletions of several chromosome regions, particularly the chromosome 8 short arm. Large-scale numerical aberrations, reflected in aberrant DNA ploidy, are also found in a minority of cases. However, it is unclear whether prostate carcinomas contain aberrations of certain chromosome regions that are deleted frequently in other common types of cancer. In this study, we performed dual-color fluorescence in situ hybridization on intact nuclei from touch preparations of 16 prostate cancers. Chromosome copy number was determined using pericentromeric probes, whereas potential chromosome arm deletions were evaluated using yeast artificial chromosome (YAC) and P1 probes. Two YAC probes targeted chromosome 8 short arm regions known to be deleted frequently in prostate cancer. Other YACs and P1s were for chromosome regions, including 1p22, 3p14, 6q21, 9p21, and 22q12, that are deletion targets in a variety of cancers although not extensively studied in prostate cancer. Hybridization efficiencies and signal intensities were excellent for both repeat sequence (alpha-satellite) and single, copy (YAC and P1) fluorescence in situ hybridization probes. Of 16 prostate cancers, 11 had clonal aberrations of 1 or more of the 13 chromosome regions evaluated, and 10 cases (62.5%) had 8p deletions, including 4 cases with 8p deletion in virtually all cells and aneuploidy in only a subset of those deleted cells. Deletions at 3p14, 6q21, and 22q12 were identified in 2, 1, and 1 case, respectively, and each of those cases had a similarly sized cell population with 8p deletion. These studies confirm 8p deletion in the majority of prostate carcinomas. 8p deletions appear to be early events in prostate tumorigenesis, often antedating aneuploidy. Fluorescence in situ hybridization strategies incorporating pericentromeric and single-copy regional chromosome probes offer a powerful and efficient means for determining frequency and progression of oncogenetic events in prostate cancer.

The adaptive immune system promotes initiation of prostate carcinogenesis in a human c-Myc transgenic mouse model.

PubMed

Melis, Monique H M; Nevedomskaya, Ekaterina; van Burgsteden, Johan; Cioni, Bianca; van Zeeburg, Hester J T; Song, Ji-Ying; Zevenhoven, John; Hawinkels, Lukas J A C; de Visser, Karin E; Bergman, Andries M

2017-11-07

Increasing evidence from epidemiological and pathological studies suggests a role of the immune system in the initiation and progression of multiple cancers, including prostate cancer. Reports on the contribution of the adaptive immune system are contradictive, since both suppression and acceleration of disease development have been reported. This study addresses the functional role of lymphocytes in prostate cancer development using a genetically engineered mouse model (GEMM) of human c-Myc driven prostate cancer (Hi-Myc mice) combined with B and T cell deficiency (RAG1 -/- mice). From a pre-cancerous stage on, Hi-Myc mice showed higher accumulation of immune cells in their prostates then wild-type mice, of which macrophages were the most abundant. The onset of invasive adenocarcinoma was delayed in Hi-MycRAG1 -/- compared to Hi-Myc mice and associated with decreased infiltration of leukocytes into the prostate. In addition, lower levels of the cytokines CXCL2, CCL5 and TGF-β1 were detected in Hi-MycRAG1 -/- compared to Hi-Myc mouse prostates. These results from a GEMM of prostate cancer provide new insights into the promoting role of the adaptive immune system in prostate cancer development. Our findings indicate that the endogenous adaptive immune system does not protect against de novo prostate carcinogenesis in Hi-Myc transgenic mice, but rather accelerates the formation of invasive adenocarcinomas. This may have implications for the development of novel treatment strategies.

Radioligand therapy of metastatic castration-resistant prostate cancer: current approaches.

PubMed

Awang, Zool Hilmi; Essler, Markus; Ahmadzadehfar, Hojjat

2018-05-23

Prostate Cancer is the forth most common type of cancer. Prostate-specific membrane antigen (PSMA) is anchored in the cell membrane of prostate epithelial cells. PSMA is highly expressed on prostate epithelial cells and strongly up-regulated in prostate cancer. Therefore it is an appropriate target for diagnostic and therapy of prostate cancer and its metastases. This article discusses several articles on radionuclide treatments in prostate cancer and the results on PSMA therapy with either beta or alpha emitters as a salvage therapy.

Altered mitochondrial genome content signals worse pathology and prognosis in prostate cancer.

PubMed

Kalsbeek, Anton M F; Chan, Eva K F; Grogan, Judith; Petersen, Desiree C; Jaratlerdsiri, Weerachai; Gupta, Ruta; Lyons, Ruth J; Haynes, Anne-Maree; Horvath, Lisa G; Kench, James G; Stricker, Phillip D; Hayes, Vanessa M

2018-01-01

Mitochondrial genome (mtDNA) content is depleted in many cancers. In prostate cancer, there is intra-glandular as well as inter-patient mtDNA copy number variation. In this study, we determine if mtDNA content can be used as a predictor for prostate cancer staging and outcomes. Fresh prostate cancer biopsies from 115 patients were obtained at time of surgery. All cores underwent pathological review, followed by isolation of cancer and normal tissue. DNA was extracted and qPCR performed to quantify the total amount of mtDNA as a ratio to genomic DNA. Differences in mtDNA content were compared for prostate cancer pathology features and disease outcomes. We showed a significantly reduced mtDNA content in prostate cancer compared with normal adjacent prostate tissue (mean difference 1.73-fold, P-value <0.001). Prostate cancer with increased mtDNA content showed unfavorable pathologic characteristics including, higher disease stage (PT2 vs PT3 P-value = 0.018), extracapsular extension (P-value = 0.02) and a trend toward an increased Gleason score (P-value = 0.064). No significant association was observed between changes in mtDNA content and biochemical recurrence (median follow up of 107 months). Contrary to other cancer types, prostate cancer tissue shows no universally depleted mtDNA content. Rather, the change in mtDNA content is highly variable, mirroring known prostate cancer genome heterogeneity. Patients with high mtDNA content have an unfavorable pathology, while a high mtDNA content in normal adjacent prostate tissue is associated with worse prognosis. © 2017 Wiley Periodicals, Inc.

SRD5A1 and SRD5A2 are associated with treatment for benign prostatic hyperplasia with the combination of 5α-reductase inhibitors and α-adrenergic receptor antagonists.

PubMed

Gu, Xin; Na, Rong; Huang, Tao; Wang, Li; Tao, Sha; Tian, Lu; Chen, Zhuo; Jiao, Yang; Kang, Jian; Zheng, Siqun; Xu, Jianfeng; Sun, Jielin; Qi, Jun

2013-08-01

Common treatments for benign prostatic hyperplasia include 5α-reductase inhibitors and α-adrenergic receptor antagonists. However, these treatments can only partially decrease the risk of benign prostatic hyperplasia progression. SRD5A1 and SRD5A2 are 5α-reductase inhibitor targets. We investigated the association between drug efficacy and single nucleotide polymorphisms in the SRD5A1 and SRD5A2 genes in a Chinese population. We genotyped 11 tagging single nucleotide polymorphisms in the SRD5A1 and SRD5A2 genes in a total of 426 benign prostatic hyperplasia cases and 1,008 controls from Xinhua Hospital, Shanghai, People's Republic of China. Cases were treated with type II 5α-reductase inhibitors and α-adrenergic receptor antagonists. We tested the association of tagging single nucleotide polymorphisms with benign prostatic hyperplasia risk/progression, clinical characteristics at baseline, including the I-PSS (International Prostate Symptom Score) and total prostate volume, and changes in clinical characteristics after treatment. The 11 tagging single nucleotide polymorphisms were not significantly associated with benign prostatic hyperplasia risk or progression (each p >0.05). In the SRD5A1 gene rs6884552 and rs3797177 were significantly associated with baseline I-PSS (p = 0.04 and 0.003, respectively). In the SRD5A2 gene rs523349 (V89L) and rs9332975 were significantly associated with baseline total prostate volume (p = 0.01 and 0.001, respectively). In SRD5A1 rs166050 was significantly associated with the posttreatment change in total prostate volume (p = 0.04). In SRD5A2 rs523349 and rs612224 were significantly associated with the posttreatment I-PSS change (p = 0.03 and 0.009, respectively). SRD5A1 and SRD5A2 single nucleotide polymorphisms are significantly associated with the clinical characteristics of benign prostatic hyperplasia and the efficacy of benign prostatic hyperplasia treatment. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

[Role of angiotensin II receptor type 2 in predicting biochemical recurrence in the treatment of prostate cancer].

PubMed

Chibichyan, M B; Kogan, M I; Chernogubova, E A; Pavlenko, I A; Matishov, D G

2016-12-01

To identify markers for predicting aggressive forms of prostate cancer. The study retrospectively evaluated expression of angiotensin II type 2 receptors (AT2-R) in prostate needle biopsy tissue from patients with and without biochemical recurrence after combined hormone and radiation therapy. The study findings showed that low expression of AT2-R in prostate tissue was associated with a high risk of biochemical recurrence. The data on the nature of AT2-R expression in prostate tissue of prostate cancer patients may be considered as a tool for predicting biochemical recurrence after combined hormone and radiation therapy. The test has a sensitivity of 87.5% and specificity of 85.71%.

High milk consumption does not affect prostate tumor progression in two mouse models of benign and neoplastic lesions.

PubMed

Bernichtein, Sophie; Pigat, Natascha; Capiod, Thierry; Boutillon, Florence; Verkarre, Virginie; Camparo, Philippe; Viltard, Mélanie; Méjean, Arnaud; Oudard, Stéphane; Souberbielle, Jean-Claude; Friedlander, Gérard; Goffin, Vincent

2015-01-01

Epidemiological studies that have investigated whether dairy (mainly milk) diets are associated with prostate cancer risk have led to controversial conclusions. In addition, no existing study clearly evaluated the effects of dairy/milk diets on prostate tumor progression, which is clinically highly relevant in view of the millions of men presenting with prostate pathologies worldwide, including benign prostate hyperplasia (BPH) or high-grade prostatic intraepithelial neoplasia (HGPIN). We report here a unique interventional animal study to address this issue. We used two mouse models of fully penetrant genetically-induced prostate tumorigenesis that were investigated at the stages of benign hyperplasia (probasin-Prl mice, Pb-Prl) or pre-cancerous PIN lesions (KIMAP mice). Mice were fed high milk diets (skim or whole) for 15 to 27 weeks of time depending on the kinetics of prostate tumor development in each model. Prostate tumor progression was assessed by tissue histopathology examination, epithelial proliferation, stromal inflammation and fibrosis, tumor invasiveness potency and expression of various tumor markers relevant for each model (c-Fes, Gprc6a, activated Stat5 and p63). Our results show that high milk consumption (either skim or whole) did not promote progression of existing prostate tumors when assessed at early stages of tumorigenesis (hyperplasia and neoplasia). For some parameters, and depending on milk type, milk regimen could even exhibit slight protective effects towards prostate tumor progression by decreasing the expression of tumor-related markers like Ki-67 and Gprc6a. In conclusion, our study suggests that regular milk consumption should not be considered detrimental for patients presenting with early-stage prostate tumors.

Virus Delivery of CRISPR Guides to the Murine Prostate for Gene Alteration.

PubMed

Riedel, Maria; Berthelsen, Martin F; Bakiri, Latifa; Wagner, Erwin F; Thomsen, Martin K

2018-04-27

With an increasing incidence of prostate cancer, identification of new tumor drivers or modulators is crucial. Genetically engineered mouse models (GEMM) for prostate cancer are hampered by tumor heterogeneity and its complex microevolution dynamics. Traditional prostate cancer mouse models include, amongst others, germline and conditional knockouts, transgenic expression of oncogenes, and xenograft models. Generation of de novo mutations in these models is complex, time-consuming, and costly. In addition, most of traditional models target the majority of the prostate epithelium, whereas human prostate cancer is well known to evolve as an isolated event in only a small subset of cells. Valuable models need to simulate not only prostate cancer initiation, but also progression to advanced disease. Here we describe a method to target a few cells in the prostate epithelium by transducing cells by viral particles. The delivery of an engineered virus to the murine prostate allows alteration of gene expression in the prostate epithelia. Virus type and quantity will hereby define the number of targeted cells for gene alteration by transducing a few cells for cancer initiation and many cells for gene therapy. Through surgery-based injection in the anterior lobe, distal from the urinary track, the tumor in this model can expand without impairing the urinary function of the animal. Furthermore, by targeting only a subset of prostate epithelial cells the technique enables clonal expansion of the tumor, and therefore mimics human tumor initiation, progression, as well as invasion through the basal membrane. This novel technique provides a powerful prostate cancer model with improved physiological relevance. Animal suffering is limited, and since no additional breeding is required, overall animal count is reduced. At the same time, analysis of new candidate genes and pathways is accelerated, which in turn is more cost efficient.

Identification of activated enhancers and linked transcription factors in breast, prostate, and kidney tumors by tracing enhancer networks using epigenetic traits.

PubMed

Rhie, Suhn Kyong; Guo, Yu; Tak, Yu Gyoung; Yao, Lijing; Shen, Hui; Coetzee, Gerhard A; Laird, Peter W; Farnham, Peggy J

2016-01-01

Although technological advances now allow increased tumor profiling, a detailed understanding of the mechanisms leading to the development of different cancers remains elusive. Our approach toward understanding the molecular events that lead to cancer is to characterize changes in transcriptional regulatory networks between normal and tumor tissue. Because enhancer activity is thought to be critical in regulating cell fate decisions, we have focused our studies on distal regulatory elements and transcription factors that bind to these elements. Using DNA methylation data, we identified more than 25,000 enhancers that are differentially activated in breast, prostate, and kidney tumor tissues, as compared to normal tissues. We then developed an analytical approach called Tracing Enhancer Networks using Epigenetic Traits that correlates DNA methylation levels at enhancers with gene expression to identify more than 800,000 genome-wide links from enhancers to genes and from genes to enhancers. We found more than 1200 transcription factors to be involved in these tumor-specific enhancer networks. We further characterized several transcription factors linked to a large number of enhancers in each tumor type, including GATA3 in non-basal breast tumors, HOXC6 and DLX1 in prostate tumors, and ZNF395 in kidney tumors. We showed that HOXC6 and DLX1 are associated with different clusters of prostate tumor-specific enhancers and confer distinct transcriptomic changes upon knockdown in C42B prostate cancer cells. We also discovered de novo motifs enriched in enhancers linked to ZNF395 in kidney tumors. Our studies characterized tumor-specific enhancers and revealed key transcription factors involved in enhancer networks for specific tumor types and subgroups. Our findings, which include a large set of identified enhancers and transcription factors linked to those enhancers in breast, prostate, and kidney cancers, will facilitate understanding of enhancer networks and mechanisms leading to the development of these cancers.

Is effective a prior multiparametric magnetic resonance scan in patients candidates to prostate biopsy? CAT Study.

PubMed

Ramos Rodríguez, J R; Molinero Pérez, M; Herrera Imbroda, B; Domínguez Pinos, M D

2016-01-01

We carried out a critically appraised topic (CAT)-type study to determine whether the relevant scientific evidence supports the recommendation of doing a multiparametric magnetic resonance imaging study of the prostate in all patients who are candidates for prostate biopsy with the aim of improving the detection of clinically significant prostate cancer and stratifying patients to receive active surveillance or treatment. After a formal literature search and an analysis of the two most relevant articles it found, we reached the conclusion that, despite promising results that point to the potential usefulness of this approach, there is still not enough clear scientific evidence to endorse it categorically. Before this approach can be endorsed, we need evidence from well-designed prospective randomized trials using widely agreed upon criteria and including large numbers of patients at multiple centers. Copyright © 2016 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

An ESIPT fluorescent probe sensitive to protein α-helix structures.

PubMed

Jiang, Nan; Yang, Chanli; Dong, Xiongwei; Sun, Xianglang; Zhang, Dan; Liu, Changlin

2014-07-28

A large majority of membrane proteins have one or more transmembrane regions consisting of α-helices. Membrane protein levels differ from one type of cell to another, and the expression of membrane proteins also changes from normal to diseased cells. For example, prostate cancer cells have been reported to have downregulated expression of membrane proteins, including zinc transporters, compared with normal prostate cells. These reports inspired us to design a fluorescence probe sensitive to protein α-helical structures to discriminate individual prostate cancer cells from normal ones. A benzazole derivative ( in this study) was observed to emit strong fluorescence resulting from an excited-state intramolecular proton transfer (ESIPT) in protein α-helical environments. The intensity of ESIPT fluorescence of was observed to be positively correlated with the α-helix content of proteins. The molecular docking simulation suggested that it had low energy for the binding of to proteins when the binding sites were localized within the α-helical regions of protein via H-bonds. Furthermore, was found to be localized in cell membranes through binding to transmembrane α-helical regions of membrane proteins, and was capable of probing differences in the α-helix contents of membrane proteins between normal and cancerous prostate cells through changes in the ESIPT emission intensity. These results indicated that could distinguish individual prostate cancer cells from normal ones, as the changes in the ESIPT fluorescence intensity of could reflect the regulation in expression of the membrane proteins including zinc transporters. This recognition strategy of individual prostate cancer cells might contribute to early diagnosis techniques for prostate cancer.

Neuroendocrine-type prostatic adenocarcinoma with microsatellite instability in a patient with lynch syndrome.

PubMed

Wagner, David G; Gatalica, Zoran; Lynch, Henry T; Kohl, Shane; Johansson, Sonny L; Lele, Subodh M

2010-12-01

Lynch syndrome is an autosomal-dominant cancer syndrome that can be identified with microsatellite instability molecular tests or immunohistochemical stains on pathologic material from patients who meet the Amsterdam Criteria II. The development of prostatic carcinoma in situ or invasive small cell carcinoma (SCC) of the prostate has not been previously reported in a patient with this syndrome. In this report, an 87-year-old White man with the Lynch syndrome had a prostate biopsy that revealed a mixed high-grade conventional adenocarcinoma and SCC of the prostate with high-grade prostatic intraepithelial neoplasia of the small cell neuroendocrine-type (HGPIN-NE), all showing MSH2 microsatellite instability and loss of MSH2 expression, a finding not previously published. These findings suggest that HGPIN-NE is a precursor of invasive SCC and also that prostatic SCC can develop in a patient with the Lynch syndrome.

[Application evaluation of multi-parametric MRI in the diagnosis and differential diagnosis of early prostate cancer and prostatitis].

PubMed

Li, P; Huang, Y; Li, Y; Cai, L; Ji, G H; Zheng, Y; Chen, Z Q

2016-10-11

Objective: To evaluate the value of multi-parametric MRI (Mp-MRI) in the diagnosis and differential diagnosis of early prostate cancer(PCa) in the peripheral zone(PZ) and low T 2 WI signal intensity of prostatitis. Methods: A total of 40 patients with PZ early PCa and 37 with prostatitis of hypointense T 2 WI signal in PZ were retrospectively analyzed, which were collected from the General Hospital of Ningxia Medical University from Janurary 2009 to June 2015, who underwent T 2 WI, DWI, and DCE-MRI examination and all patients were confirmed by pathology. All the data was transferred to GE Advanced Workstation AW4.3, the indexes divided into cancerous and prostatitis regions were calculated by Functool2 of signal intensity-time(SI-T) curve and ADC value, to calcuate the time to minimum(T max ), the whole enhancment degree (SI max ). ROC cure was used to determine the cutoff value for PCa detection with the ADC value. Result: On T 2 WI, 57.5% of PCa (23/40) showed focal nodular homogeneous low signal intensity, 70.3% of prostatitis(26/37) showed diffuse inhomogeneous low signal intensity. DCE-MRI, the distribution of curve types for malignant tumors was type Ⅰ 2.5%(1/40), typeⅡ32.5%(13/40) and type Ⅲ 65.0% (26/40). While the numbers for prostatitis was type Ⅰ 16.2%(6/37) , type Ⅱ 56.8% (21/37) and type Ⅲ 27.0% (10/37)respectively.The patterns of curve types in malignant lesions were different from benign lesions significantly(χ 2 =12.32, P <0.01). The mean values of T max , SI max in cancerous and prostatitis regions were (17.96±2.91)s, 1.76%±0.23% and (21.19±3.59)s, 1.53%±0.18%, respectively ( t =5.37, 6.10; P <0.01). On DWI, The mean ADC values in cancerous and prostatitis regions were (0.95±0.13)×10 -3 mm 2 /s and (1.12±0.13)×10 -3 mm 2 /s, respectively ( t =7.10, P <0.01). According to the ROC analysis, when the cutoff value was 1.01×10 -3 mm 2 /s, the early PCa of diagnostic sensitivity, specificity and accuracy was 79.1%, 72.7% and 76.1% respectively. Conclusion: Combined with morphology and signal characteristics of conventional T 2 WI, DWI and DCE-MRI improve the power of MR imaging in discriminating prostatitis from early PCa.

Fiducial marker guided prostate radiotherapy: a review

PubMed Central

Jain, Suneil; Hounsell, Alan R; O'Sullivan, Joe M

2016-01-01

Image-guided radiotherapy (IGRT) is an essential tool in the accurate delivery of modern radiotherapy techniques. Prostate radiotherapy positioned using skin marks or bony anatomy may be adequate for delivering a relatively homogeneous whole-pelvic radiotherapy dose, but these surrogates are not reliable when using reduced margins, dose escalation or hypofractionated stereotactic radiotherapy. Fiducial markers (FMs) for prostate IGRT have been in use since the 1990s. They require surgical implantation and provide a surrogate for the position of the prostate gland. A variety of FMs are available and they can be used in a number of ways. This review aimed to establish the evidence for using prostate FMs in terms of feasibility, implantation procedures, types of FMs used, FM migration, imaging modalities used and the clinical impact of FMs. A search strategy was defined and a literature search was carried out in Medline. Inclusion and exclusion criteria were applied, which resulted in 50 articles being included in this review. The evidence demonstrates that FMs provide a more accurate surrogate for the position of the prostate than either external skin marks or bony anatomy. A combination of FM alignment and soft-tissue analysis is currently the most effective and widely available approach to ensuring accuracy in prostate IGRT. FM implantation is safe and well tolerated. FM migration is possible but minimal. Standardization of all techniques and procedures in relation to the use of prostate FMs is required. Finally, a clinical trial investigating a non-surgical alternative to prostate FMs is introduced. PMID:27585736

Recent advances in prostate development and links to prostatic diseases

PubMed Central

Powers, Ginny L.

2013-01-01

The prostate is a branched ductal-acinar gland that is part of the male reproductive tract. Prostate development depends upon the integration of steroid hormone signals, paracrine interactions between the stromal and epithelial tissue layers, and the actions of cell autonomous factors. Several genes and signalling pathways are known to be required for one or more steps of prostate development including epithelial budding, duct elongation, branching morphogenesis, and/or cellular differentiation. Recent progress in the field of prostate development has included the application of genome-wide technologies including serial analysis of gene expression (SAGE), expression profiling microarrays, and other large scale approaches to identify new genes and pathways that are essential for prostate development. The aggregation of experimental results into online databases by organized multi-lab projects including the Genitourinary Developmental Molecular Atlas Project (GUDMAP) has also accelerated the understanding of molecular pathways that function during prostate development and identified links between prostate anatomy and molecular signaling. Rapid progress has also recently been made in understanding the nature and role of candidate stem cells in the developing and adult prostate. This has included the identification of putative prostate stem cell markers, lineage tracing, and organ reconstitution studies. However, several issues regarding their origin, precise nature, and possible role(s) in disease remain unresolved. Nevertheless, several links between prostatic developmental mechanisms and the pathogenesis of prostatic diseases including benign prostatic hyperplasia and prostate cancer have led to recent progress on targeting developmental pathways as therapeutic strategies for these diseases. PMID:23335485

Analysis of the MDM2 antagonist nutlin-3 in human prostate cancer cells.

PubMed

Logan, Ian R; McNeill, Hesta V; Cook, Susan; Lu, Xiaohong; Lunec, John; Robson, Craig N

2007-06-01

Small molecule MDM2 antagonists including nutlin-3 have been shown to be effective against a range of cancer cell types and nutlin-3 can inhibit growth of LNCaP xenografts. We compared the efficacy of nutlin-3 in three prostate cancer cell types and provide an insight into the mechanism of nutlin-3. Nutlin-3 efficacy was measured using proliferation assays, cell cycle analysis, apoptosis assays, quantitative RT-PCR, and immunoblotting. Chromatin immunoprecipitation (ChIP) assays were also performed. Nutlin-3 can specifically inhibit proliferation of LNCaP cells through cell cycle arrest and apoptosis. This coincides with increased levels of the p53-responsive transcripts p21, PUMA, gadd45, and Mdm2 and recruitment of p53 to chromatin. Nutlin-3 also reduces androgen receptor levels, resulting in altered receptor recruitment to chromatin. Our study demonstrates that small molecule MDM2 antagonists might be useful in the treatment of human prostate cancers that retain functional p53 and androgen receptor signaling. Copyright 2007 Wiley-Liss, Inc.

Familial transmission of prostate, breast and colorectal cancer in adoptees is related to cancer in biological but not in adoptive parents: a nationwide family study.

PubMed

Zöller, Bengt; Li, Xinjun; Sundquist, Jan; Sundquist, Kristina

2014-09-01

Familial clustering of prostate, breast and colorectal cancer is well established, but the familial risk of these cancers has not been determined among adoptees. The aim was to disentangle the contributions of genetic and environmental factors to the familial transmission of prostate, breast and colorectal cancer. The Swedish Multi-Generation Register was used to follow all adoptees born between 1932 and 1969 (n=70,965) for prostate, breast and colorectal cancer from January 1958 up to December 2010. The risk of prostate, breast and colorectal cancer was estimated in adoptees with at least one biological parent with the same cancer type compared with adoptees without a biological parent with the same cancer type. The risk of cancer was also determined in adoptees with at least one adoptive parent with cancer compared with adoptees with an adoptive parent without cancer. Adoptees with at least one biological parent with prostate, breast or colorectal cancer were more likely to have cancer of the same type than adoptees with biological parents not affected by these respective cancer types (standardised incidence ratio=SIR: 1.8 [95% confidence interval 1.2-2.7], 2.0 [1.6-2.5] and 1.9 [1.2-2.9], respectively). In contrast, adoptees with at least one adoptive parent with prostate, breast or colorectal cancer were not at an increased risk of these respective cancer types (SIR=1.2 [0.94-1.6], 0.97 [0.71-1.3], and 1.1 [0.71-1.5], respectively). The findings of the study support the importance of genetic/biological factors in the familial transmission of prostate, breast and colorectal cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

ONC201 Targets AR and AR-V7 Signaling, Reduces PSA, and Synergizes with Everolimus in Prostate Cancer.

PubMed

Lev, Avital; Lulla, Amriti R; Ross, Brian C; Ralff, Marie D; Makhov, Petr B; Dicker, David T; El-Deiry, Wafik S

2018-05-01

Androgen receptor (AR) signaling plays a key role in prostate cancer progression, and androgen deprivation therapy (ADT) is a mainstay clinical treatment regimen for patients with advanced disease. Unfortunately, most prostate cancers eventually become androgen-independent and resistant to ADT with patients progressing to metastatic castration-resistant prostate cancer (mCRPC). Constitutively activated AR variants (AR-V) have emerged as mediators of resistance to AR-targeted therapy and the progression of mCRPC, and they represent an important therapeutic target. Out of at least 15 AR-Vs described thus far, AR-V7 is the most abundant, and its expression correlates with ADT resistance. ONC201/TIC10 is the founding member of the imipridone class of small molecules and has shown anticancer activity in a broad range of tumor types. ONC201 is currently being tested in phase I/II clinical trials for advanced solid tumors, including mCRPC, and hematologic malignancies. There has been promising activity observed in patients in early clinical testing. This study demonstrates preclinical single-agent efficacy of ONC201 using in vitro and in vivo models of prostate cancer. ONC201 has potent antiproliferative and proapoptotic effects in both castration-resistant and -sensitive prostate cancer cells. Furthermore, the data demonstrate that ONC201 downregulates the expression of key drivers of prostate cancer such as AR-V7 and downstream target genes including the clinically used biomarker PSA (KLK3). Finally, the data also provide a preclinical rationale for combination of ONC201 with approved therapeutics for prostate cancer such as enzalutamide, everolimus (mTOR inhibitor), or docetaxel. Implications: The preclinical efficacy of ONC201 as a single agent or in combination, in hormone-sensitive or castration-resistant prostate cancer, suggests the potential for immediate clinical translation. Mol Cancer Res; 16(5); 754-66. ©2018 AACR . ©2018 American Association for Cancer Research.

The Utility of PET/CT in the Planning of External Radiation Therapy for Prostate Cancer.

PubMed

Calais, Jeremie; Cao, Minsong; Nickols, Nicholas G

2018-04-01

Radiotherapy and radical prostatectomy are the definitive treatment options for patients with localized prostate cancer. A rising level of prostate-specific antigen after radical prostatectomy indicates prostate cancer recurrence, and these patients may still be cured with salvage radiotherapy. To maximize chance for cure, the irradiated volumes should completely encompass the extent of disease. Therefore, accurate estimation of the location of disease is critical for radiotherapy planning in both the definitive and the salvage settings. Current first-line imaging for prostate cancer has limited sensitivity for detection of disease both at initial staging and at biochemical recurrence. Integration of PET into routine evaluation of prostate cancer patients may improve both staging accuracy and radiotherapy planning. 18 F-FDG PET/CT is now routinely used in radiation planning for several cancer types. However, 18 F-FDG PET/CT has low sensitivity for prostate cancer. Additional PET probes evaluated in prostate cancer include 18 F-sodium fluoride, 11 C-acetate, 11 C- or 18 F-choline, 18 F-fluciclovine, and 68 Ga- or 18 F-labeled ligands that bind prostate-specific membrane antigen (PSMA). PSMA ligands appear to be the most sensitive and specific but have not yet received Food and Drug Administration New Drug Application approval for use in the United States. Retrospective and prospective investigations suggest a potential major impact of PET/CT on prostate radiation treatment planning. Prospective trials randomizing patients to routine radiotherapy planning versus PET/CT-aided planning may show meaningful clinical outcomes. Prospective clinical trials evaluating the addition of 18 F-fluciclovine PET/CT for planning of salvage radiotherapy with clinical endpoints are under way. Prospective trials evaluating the clinical impact of PSMA PET/CT on prostate radiation planning are indicated. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

The molecular biology of prostate cancer: current understanding and clinical implications.

PubMed

Gandhi, Jason; Afridi, Adil; Vatsia, Sohrab; Joshi, Gargi; Joshi, Gunjan; Kaplan, Steven A; Smith, Noel L; Khan, Sardar Ali

2018-04-01

With continuous progress over the past few decades in understanding diagnosis, treatment, and genetics, much has been learned about the prostate cancer-diagnosed genome. A comprehensive MEDLINE® and Google scholar literature search was conducted using keyword variations relating to the genetics of prostate cancer such as chromosomal alterations, androgen receptor, castration-resistant, inheritance, polymorphisms, oncogenes, metastasis, biomarkers, and immunotherapy. Traditionally, androgen receptors (AR) have been the focus of research. Recently, identification of recurrent chromosomal alterations that lead to either multiplication of regions (gain-of-function) or deletion of regions (loss-of-function) has opened the door to greater genetic accessibility. These chromosomal aberrations lead to variation in copy number and gene expression. Some of these chromosomal alterations are inherited, while others undergo somatic mutations during disease progression. Inherited gene mutations that make one susceptible to prostate cancer have been identified with familial-linked studies. Somatic genes that progress tumorigenesis have also been identified. Research on the molecular biology of prostate cancer has characterized these genes into tumor suppressor genes or oncogenes. Additionally, genome-wide assay studies have identified many high-risk single-nucleotide polymorphisms recurrent throughout the prostate cancer-diagnosed genome. Castration-resistant prostate cancer is the most aggressive form of prostate cancer, and its research has elucidated many types of mutations associated with AR itself, including enhanced expression and amplification, point mutations, and alternative splicing. Understanding the molecular biology of prostate cancer has permitted more accurate identification using advanced biomarkers and therapy for aggressive forms using immunotherapy. An age-related disease, prostate cancer commands profound attention. With increasing life expectancy and the continuous pursuit of it, prostate cancer is a powerful obstacle best defeated using targeted therapies specifically designed for the unique molecular profile of the malignancy.

Prostate cancer in young adults-Seventeen-year clinical experience of a single center.

PubMed

Huang, Tzu-Hao; Kuo, Junne-Yih; Huang, Yi-Hsiu; Chung, Hsiao-Jen; Huang, William J S; Wu, Howard H H; Chang, Yen-Hwa; Lin, Alex T L; Chen, Kuang-Kuo

2017-01-01

In the general population, prostate adenocarcinoma affects predominately older men. If fact, most current guidelines suggest that males over the age of 50 years should undergo prostate cancer screening. However, the clinical behavior and prognosis of prostate cancer in young adults is not well defined. The aim of this study was to evaluate the clinical behavior, pathological characteristics, and prognosis of prostate cancer in young adults. We retrospectively reviewed the records of young patients (age, ≤50 years) in our hospital with prostate adenocarcinoma between 1997 and 2013. We compared data including initial presentation, cancer cell type, Gleason score, disease stage, prostate-specific antigen (PSA) level, prostate volume, treatment, and survival between patients both younger and older than 50 years. Data were analyzed using the Kaplan-Meier method to assess survival. Twenty-six patients were enrolled in our study, accounting for 0.55% of all patients with a diagnosis of prostate cancer at our facility. All 26 patients had a pathology diagnosis of adenocarcinoma, with a mean age on diagnosis of 46.8±2.8 years (range, 39-50 years). On initial presentation, patients older than 50 years more frequently displayed lower urinary tract symptoms (LUTS) than younger patients (62.3% vs. 30.4%, p=0.008). There was no statistical difference in histological grade, disease stage, PSA level, overall survival, and biochemical-free survival between the two groups. The result of our investigation indicated that prostate adenocarcinoma patients younger than 50 years had similar histological grade, disease stage, PSA level, overall survival, and biochemical-free survival as the older population. However, patients younger than 50 years with prostate cancer less frequently showed initial symptoms of LUTS. Copyright © 2016. Published by Elsevier Taiwan LLC.

Dynamic contrast enhanced MRI of the prostate: comparison of gadobutrol and Gd-DTPA.

PubMed

Durmus, T; Vollnberg, B; Schwenke, C; Kilic, E; Huppertz, A; Taupitz, M; Franiel, T

2013-09-01

To evaluate the enhancement profile of the macrocyclic contrast medium (CM) gadobutrol in comparison to linear CM Gd-DTPA in DCE-MRI of the prostate. In total 53 patients with prostata cancer (PCa) were included, who received a radical prostatectomy after multiparametric MRI of the prostate including DCE-MRI. Using circular regions of interests normal peripheral zone (PZ) and PCa foci > 5 mm in diameter (42 and 34 foci in Gd-DTPA and gadobutrol group, respectively) were analysed in DCE-MRI. Enhancement curves (Type I, II and III) and pharmacokinetic parameters were analyzed qualitatively and quantitatively and compared using mixed linear models (two sided p-values < 0.05 were regarded significant). There was no significant difference in frequencies of curve types I, II or III in the normal PZ (p = 0.63) or in PCa foci (p = 0.75). PCa with a Gleason score ≥ 7 had in comparison to Gleason ≤ 6 significantly more often a Wash-Out-curve (Type III) with both CM (p = 0.02). The relative peak enhancement was in the PZ (Gd-DTPA 1.4 a. u. [1.20; 1.59], gadobutrol 1.58 a. u. [1.37; 1.78]) and in PCa foci (Gd-DTPA 1.56 a. u. [1.41; 1.71], gadobutrol 1.76 a. u. [1.59; 1.94]) significantly higher with gadobutrol (p = 0.04). The pharmacokinetic parameters Ktrans und kep were higher in PCa foci than in PZ (p < 0.0001 and p = 0.002, respectively) without significant difference of the parameter values between both CM (p = 0.65). [corrected] This study is the first systematic comparison of gadobutrol and Gd-DTPA in DCE-MRI of the prostate. The relative peak enhancement is higher using gadobutrol compared to Gd-DTPA in DCE-MRI. There was no statistically significant difference in curve types or the pharmacokinetic parameters in PCa or normal PZ between both CM. © Georg Thieme Verlag KG Stuttgart · New York.

[Saw palmetto fruit extract improves LUTS in type ⅢA prostatitis patients].

PubMed

Shao, Yun-Peng; Xue, Hao-Liang; Shen, Bai-Xin; Ding, Liu-Cheng; Chen, Zheng-Seng; Wei, Zhong-Qing

2017-05-01

To assess the clinical efficacy of the saw palmetto fruit extract (SPFE) in the treatment of lower urinary tract symptoms (LUTS) in patients with type ⅢA prostatitis. This retrospective study included 54 cases of type ⅢA prostatitis treated in the Outpatient Department of our hospital from January to December 2015. The patients were aged 35.06 ± 5.85 years, with a mean disease course of 3.8 ± 2.1 years, and all received oral medication of SPFE Capsules at the dose of 320 mg qd for 12 weeks. We assessed the therapeutic effects by comparing the NIH-chronic prostatitis symptom indexes (NIH-CPSI), voiding diary, International Prostate Symptom Scores (IPSS), and results of urodynamic examination before and after treatment. Compared with the baseline, both NIH-CPSI and IPSS were significantly decreased after medication (27.61 ± 3.76 vs 18.6 ± 5.34, P <0.01; 20.44 ± 4.51 vs 10.96±4.62, P <0.01), and urodynamic examination and voiding diary showed dramatic post-medication improvement in the average urinary flow rate (［8.05±1.42］ vs ［12.05±2.60］ ml/s, P <0.01 ), maximum urinary flow rate (［14.22±1.74］ vs ［21.32±4.51］ ml/s, P <0.01), residual urine volume (［46.15±16.57］ vs ［14.55±10.21］ ml, P <0.01), maximum urethral closure pressure (［76.52±3.53］ vs ［65.32±4.75］ cm H2O, P <0.01), mean urinary volume (［124.63±40.55］ vs ［285.93±58.68］ ml, P <0.01), urination frequency (16.96±4.17 vs 8.96±2.50, P <0.01), and nocturia frequency (8.94±3.23 vs 3.15±1.90, P <0.01). No apparent adverse reactions were observed in any of the patients. SPFE Capsules can safely and effectively improve LUTS and thus the quality of life of patients with type ⅢA prostatitis.

Detection of human papillomavirus (HPV) DNA in human prostatic tissues by polymerase chain reaction (PCR).

PubMed

Sarkar, F H; Sakr, W A; Li, Y W; Sreepathi, P; Crissman, J D

1993-01-01

Human papillomavirus (HPV) infections are strongly linked to the pathogenesis of uterine cervical neoplasms, and have been implicated in other cancers of the female genital tract. In contrast, the association of HPV with the cancers of the male urogenital tract is less evident, except in anal and penile cancers. However, recent studies reporting the prevalence of HPV infections in human prostate cancers (60-100% HPV 16 positive vs. no infection of HPV) have raised controversies regarding the prevalence of HPV in benign and neoplastic human prostate. We investigated the prevalence of HPV infections in prostatic intraepithelial neoplasia (PIN) and prostatic adenocarcinomas in 23 surgically resected prostates. Polymerase chain reaction (PCR) was used to amplify HPV 6b/11, 16, and 18 specific DNA sequences, using type specific HPV primers selected from the transforming gene E6-E7. The areas of PIN and cancer in 6 microns H&E stained tissue sections were identified, and respective areas of PIN and cancer were isolated from the adjacent serial sections and used for DNA amplification and HPV detection (Fig. 1). Our results demonstrated the presence of HPV 16 in three carcinomas (13%), using type specific primers in PCR amplified samples. We were not able to demonstrate the presence of other HPV types (HPV 6b/11 or HPV 18) in any of the samples using specific primers. Two of these prostates showed relatively strong positive signals by dot blot analysis, when hybridized with a 32P-labeled HPV 16 type specific oligonucleotide probe. One more sample showed weak positivity, when hybridized with a 32P-labeled HPV 16 type specific oligonucleotide probe. Subsequently, we have confirmed these results by Southern hybridization of the samples transferred to nylon membrane after agarose gel electrophoresis and detected by HPV 16 type specific oligonucleotide probe, using chemiluminescent assay. We, therefore, conclude that HPV infections of the prostate in general are not as common as has been previously claimed by other investigators.

Tocotrienols and Prostate Cancer

DTIC Science & Technology

2005-09-01

W81XWH-04-1-0035 TITLE: Tocotrienols and Prostate Cancer PRINCIPAL INVESTIGATOR: William L. Stone, Ph.D...REPORT DATE (DD-MM-YYYY) September 2005 2. REPORT TYPE Final 3. DATES COVERED (From - To) 1 Mar 04 – 31 AUG 05 5a. CONTRACT NUMBER Tocotrienols ...tocopherols and tocotrienols , have variable growth inhibitory effects on both types of prostate cancer cell line models. The gamma isoforms are more

Exploiting a Molecular Gleason Grade for Prostate Cancer Therapy

DTIC Science & Technology

2009-03-01

P. (2008) The an- drogen-regulated type II serine protease TMPRSS2 is differentially expressed and mislocal- ized in prostate adenocarcinoma . J...program associated with key points of murine prostate organogenesis spanning the initial in utero induction of prostate budding through maturity. We...studies, we found no significant associations with stages of lung morphogenesis. Genes altered in murine prostate adenocarcinoma map to the branching

Comparison of prostate contours between conventional stepping transverse imaging and Twister-based sagittal imaging in permanent interstitial prostate brachytherapy.

PubMed

Kawakami, Shogo; Ishiyama, Hiromichi; Satoh, Takefumi; Tsumura, Hideyasu; Sekiguchi, Akane; Takenaka, Kouji; Tabata, Ken-Ichi; Iwamura, Masatsugu; Hayakawa, Kazushige

2017-08-01

To compare prostate contours on conventional stepping transverse image acquisitions with those on twister-based sagittal image acquisitions. Twenty prostate cancer patients who were planned to have permanent interstitial prostate brachytherapy were prospectively accrued. A transrectal ultrasonography probe was inserted, with the patient in lithotomy position. Transverse images were obtained with stepping movement of the transverse transducer. In the same patient, sagittal images were also obtained through rotation of the sagittal transducer using the "Twister" mode. The differences of prostate size among the two types of image acquisitions were compared. The relationships among the difference of the two types of image acquisitions, dose-volume histogram (DVH) parameters on the post-implant computed tomography (CT) analysis, as well as other factors were analyzed. The sagittal image acquisitions showed a larger prostate size compared to the transverse image acquisitions especially in the anterior-posterior (AP) direction ( p < 0.05). Interestingly, relative size of prostate apex in AP direction in sagittal image acquisitions compared to that in transverse image acquisitions was correlated to DVH parameters such as D 90 ( R = 0.518, p = 0.019), and V 100 ( R = 0.598, p = 0.005). There were small but significant differences in the prostate contours between the transverse and the sagittal planning image acquisitions. Furthermore, our study suggested that the differences between the two types of image acquisitions might correlated to dosimetric results on CT analysis.

An endocrine pathway in the prostate, ERbeta, AR, 5alpha-androstane-3beta,17beta-diol, and CYP7B1, regulates prostate growth.

PubMed

Weihua, Zhang; Lathe, Richard; Warner, Margaret; Gustafsson, Jan-Ake

2002-10-15

Epithelial proliferation of the ventral prostate in rodents peaks between 2 and 4 weeks of age, and by week 8, proliferating cells are rare. We have used ERbeta(-/-) and CYP7B1(-/-) mice to investigate the role of ERbeta and one of its ligands, 5alpha-androstane-3beta,17beta-diol (3betaAdiol), in growth of the ventral prostate. Before puberty, ERbeta was found in quiescent but not in proliferating cells, and proliferating cells occurred more frequently in ventral prostates of ERbeta(-/-) mice than in wild-type littermates. Treatment with 3betaAdiol decreased proliferation in wild-type but not in ERbeta(-/-) mice. In rats, treatment with 3betaAdiol from postnatal day 2 to 28 resulted in reduction in growth of ventral prostates. The prostates of CYP7B1(-/-) mice were hypoproliferative before puberty and smaller than those of their wild-type littermates after puberty. Because CYP7B1 represents the major pathway for inactivating 3betaAdiol in the prostate, we suggest that ERbeta, 3betaAdiol, and CYP7B1 are the components of a pathway that regulates growth of the rodent ventral prostate. In this pathway, ERbeta is an antiproliferative receptor, 3betaAdiol is an ERbeta ligand, and CYP7B1 is the enzyme that regulates ERbeta function by regulating the level of 3betaAdiol.

Transcriptional Activation by NFκB Increases Perlecan/HSPG2 Expression in the Desmoplastic Prostate Tumor Microenvironment

PubMed Central

Warren, Curtis R.; Grindel, Brian J.; Francis, Lewis; Carson, Daniel D.; Farach-Carson, Mary C.

2014-01-01

Perlecan/HSPG2, a heparan sulfate proteoglycan typically found at tissue borders including those separating epithelia and connective tissue, increases near sites of invasion of primary prostatic tumors as previously shown for other proteins involved in desmoplastic tissue reaction. Studies of prostate cancer cells and stromal cells from both prostate and bone, the major site for prostate cancer metastasis, showed that cancer cells and a subset of stromal cells increased production of perlecan in response to cytokines present in the tumor microenvironment. In silico analysis of the HSPG2 promoter revealed two conserved NFκB binding sites, in addition to the previously reported SMAD3 binding sites. By systematically transfecting cells with a variety of reporter constructs including sequences up to 2.6 kb from the start site of transcription, we identified an active cis element in the distal region of the HSPG2 promoter, and showed that it functions in regulating transcription of HSPG2. Treatment with TNF-α and/or TGFβ1 identified TNF-α as a major cytokine regulator of perlecan production. TNF-α treatment also triggered p65 nuclear translocation and binding to the HSPG2 regulatory region in stromal cells and cancer cells. In addition to stromal induction of perlecan production in the prostate, we identified a matrix-secreting bone marrow stromal cell type that may represent the source for increases in perlecan in the metastatic bone marrow environment. These studies implicate perlecan in cytokine-mediated, innate tissue responses to cancer cell invasion, a process we suggest reflects a modified wound healing tissue response co-opted by prostate cancer cells. PMID:24700612

Combination Therapy Improves Survival in Prostate Cancer Model | Center for Cancer Research

Cancer.gov

Surgery and radiotherapy are the recommended treatments for localized prostate cancer. Recurrent prostate cancer, however, is often treated with androgen-deprivation therapy. Most patients who undergo this type of therapy eventually develop castration-resistant prostate cancer (CRPC). Though initially androgen-related therapies for CRPC had been thought to be ineffective,

Sexual Health Concerns Among Cancer Survivors: Testing a Novel Information-Need Measure Among Breast and Prostate Cancer Patients.

PubMed

Crowley, Sheila A; Foley, Sallie M; Wittmann, Daniela; Jagielski, Christina H; Dunn, Rodney L; Clark, Patricia M; Griggs, Jennifer J; Peterson, Catherine; Leonard, Marcia; An, Lawrence C; Wei, John T; Montie, James E; Janz, Nancy K

2016-09-01

While it is recognized that cancer treatment can contribute to problems in sexual function, much less is currently known about the specific sexual health concerns and information needs of cancer survivors. This study tested a new instrument to measure cancer survivors' sexual health concerns and needs for sexual information after cancer treatment. The Information on Sexual Health: Your Needs after Cancer (InSYNC), developed by a multidisciplinary team of experts, is a novel 12-item questionnaire to measure sexual health concerns and information needs of cancer survivors. We tested the measure with a sample of breast and prostate cancer survivors. A convenience sample of 114 cancer survivors (58 breast, 56 prostate) was enrolled. Results of the InSYNC questionnaire showed high levels of sexual concern among cancer survivors. Areas of concern differed by cancer type. Prostate cancer survivors were most concerned about being able to satisfy their partners (57 %) while breast cancer survivors were most concerned with changes in how their bodies worked sexually (46 %). Approximately 35 % of all cancer survivors wanted more information about sexual health. Sexual health concerns and unmet information needs are common among breast and prostate cancer survivors, varying in some aspects by type of cancer. Routine screening for sexual health concerns should be included in comprehensive cancer survivorship care to appropriately address health care needs. The InSYNC questionnaire is one tool that may help clinicians identify concerns facing their patients.

Methodological aspects of the molecular and histological study of prostate cancer: focus on PTEN.

PubMed

Ugalde-Olano, Aitziber; Egia, Ainara; Fernández-Ruiz, Sonia; Loizaga-Iriarte, Ana; Zuñiga-García, Patricia; Garcia, Stephane; Royo, Félix; Lacasa-Viscasillas, Isabel; Castro, Erika; Cortazar, Ana R; Zabala-Letona, Amaia; Martín-Martín, Natalia; Arruabarrena-Aristorena, Amaia; Torrano-Moya, Verónica; Valcárcel-Jiménez, Lorea; Sánchez-Mosquera, Pilar; Caro-Maldonado, Alfredo; González-Tampan, Jorge; Cachi-Fuentes, Guido; Bilbao, Elena; Montero, Rocío; Fernández, Sara; Arrieta, Edurne; Zorroza, Kerman; Castillo-Martín, Mireia; Serra, Violeta; Salazar, Eider; Macías-Cámara, Nuria; Tabernero, Jose; Baselga, Jose; Cordón-Cardo, Carlos; Aransay, Ana M; Villar, Amaia Del; Iovanna, Juan L; Falcón-Pérez, Juan M; Unda, Miguel; Bilbao, Roberto; Carracedo, Arkaitz

2015-05-01

Prostate cancer is among the most frequent cancers in men, and despite its high rate of cure, the high number of cases results in an elevated mortality worldwide. Importantly, prostate cancer incidence is dramatically increasing in western societies in the past decades, suggesting that this type of tumor is exquisitely sensitive to lifestyle changes. Prostate cancer frequently exhibits alterations in the PTEN gene (inactivating mutations or gene deletions) or at the protein level (reduced protein expression or altered sub-cellular compartmentalization). The relevance of PTEN in this type of cancer is further supported by the fact that the sole deletion of PTEN in the murine prostate epithelium recapitulates many of the features of the human disease. In order to study the molecular alterations in prostate cancer, we need to overcome the methodological challenges that this tissue imposes. In this review we present protocols and methods, using PTEN as proof of concept, to study different molecular characteristics of prostate cancer. Copyright © 2015. Published by Elsevier Inc.

Beyond T and DHT - Novel Steroid Derivatives Capable of Wild Type Androgen Receptor Activation

PubMed Central

Mostaghel, Elahe A

2014-01-01

While androgen deprivation therapy (ADT) remains the primary treatment for metastatic prostate cancer (PCa), castration does not eliminate androgens from the prostate tumor microenvironment, and residual intratumoral androgens are implicated in nearly every mechanism by which androgen receptor (AR)-mediated signaling promotes castration-resistant disease. The uptake and intratumoral (intracrine) conversion of circulating adrenal androgens such as dehydroepiandrosterone sulfate (DHEA-S) to steroids capable of activating the wild type AR is a recognized driver of castration resistant prostate cancer (CRPC). However, less well-characterized adrenal steroids, including 11-deoxcorticosterone (DOC) and 11beta-hydroxyandrostenedione (11OH-AED) may also play a previously unrecognized role in promoting AR activation. In particular, recent data demonstrate that the 5α-reduced metabolites of DOC and 11OH-AED are activators of the wild type AR. Given the well-recognized presence of SRD5A activity in CRPC tissue, these observations suggest that in the low androgen environment of CRPC, alternative sources of 5α-reduced ligands may supplement AR activation normally mediated by the canonical 5α-reduced agonist, 5α-DHT. Herein we review the emerging data that suggests a role for these alternative steroids of adrenal origin in activating the AR, and discuss the enzymatic pathways and novel downstream metabolites mediating these effects. We conclude by discussing the potential implications of these findings for CRPC progression, particularly in context of new agents such as abiraterone and enzalutamide which target the AR-axis for prostate cancer therapy. PMID:24948873

IgG4-related prostatitis progressed from localized IgG4-related lymphadenopathy.

PubMed

Li, Dujuan; Kan, Yunzhen; Fu, Fangfang; Wang, Shuhuan; Shi, Ligang; Liu, Jie; Kong, Lingfei

2015-01-01

Immunoglobulin G4-related disease (IgG4-RD) is a recently described inflammatory disease involving multiple organs. Prostate involvement with IgG4-RD is very rare. In this report, we describe a case of IgG4-related prostatitis progressed from localized IgG4-related lymphadenopathy. This patient was present with urine retention symptoms. MRI and CT examination revealed the prostatic enlargement and the multiple lymphadenopathy. Serum IgG4 levels were elevated. Prostatic tissue samples resected both this time and less than 1 year earlier showed the same histological type of prostatitis with histopathologic and immunohistochemical findings characteristic of IgG4-RD. The right submandibular lymph nodes excised 2 years earlier were eventually proven to be follicular hyperplasia-type IgG4-related lymphadenopathy. This is the first case of IgG4-RD that began as localized IgG4-related lymphadenopathy and progressed into a systemic disease involving prostate and multiple lymph nodes. This patient showed a good response to steroid therapy. This leads us to advocate a novel pathogenesis of prostatitis, and a novel therapeutic approach against prostatitis. Pathologists and urologists should consider this disease entity in the patients with elevated serum IgG4 levels and the symptoms of prostatic hyperplasia to avoid ineffective medical or unnecessary surgical treatment.

A case report of prostate cancer metastasis to the stomach resembling undifferentiated-type early gastric cancer.

PubMed

Inagaki, Chiaki; Suzuki, Takuto; Kitagawa, Yoshiyasu; Hara, Taro; Yamaguchi, Taketo

2017-08-07

Occurrence of metastatic cancer to the stomach is rare, particularly in patients with prostate cancer. Gastric metastasis generally presents as a solitary and submucosal lesion with a central depression. We describe a case of gastric metastasis arising from prostate cancer, which is almost indistinguishable from the undifferentiated-type gastric cancer. A definitive diagnosis was not made until endoscopic resection. On performing both conventional and magnifying endoscopies, the lesion appeared to be slightly depressed and discolored area and it could not be distinguished from undifferentiated early gastric cancer. Biopsy from the lesion was negative for immunohistochemical staining of prostate-specific antigen, a sensitive and specific marker for prostate cancer. Thus, false initial diagnosis of an early primary gastric cancer was made and endoscopic submucosal dissection was performed. Pathological findings from the resected specimen aroused suspicion of a metastatic lesion. Consequently, immunostaining was performed. The lesion was positive for prostate-specific acid phosphatase and negative for prostate-specific antigen, cytokeratin 7, and cytokeratin 20. Accordingly, the final diagnosis was a metastatic gastric lesion originating from prostate cancer. In this patient, the definitive diagnosis as a metastatic lesion was difficult due to its unusual endoscopic appearance and the negative stain for prostate-specific antigen. We postulate that both of these are consequences of hormonal therapy against prostate cancer.

Benign Prostatic Hyperplasia: A New Metabolic Disease of the Aging Male and Its Correlation with Sexual Dysfunctions

PubMed Central

Corona, Giovanni; Vignozzi, Linda; Lotti, Francesco; Cipriani, Sarah

2014-01-01

Metabolic syndrome (MetS) is a well-recognized cluster of cardiovascular (CV) risk factors including obesity, hypertension, dyslipidemia, and hyperglycaemia, closely associated with an increased risk of forthcoming cardiovascular disease and type 2 diabetes mellitus. Emerging evidence indicates that benign prostate hyperplasia (BPH) and its related lower urinary tract symptoms (LUTS) represent other clinical conditions frequently observed in subjects with MetS. Several modifiable factors involved in MetS determinism, such as inadequate diet, lack of physical exercise, and smoking and drinking behaviours are emerging as main contributors to the development of BPH. The pathogenetic mechanisms underlying the connection between MetS and BPH have not been completely clarified. MetS and its components, hypogonadism, and prostate inflammation probably play an important role in inducing BPH/LUTS. Although historically considered as a “normal” consequence of the aging process, BPH/LUTS should now be faced proactively, as a preventable disorder of the elderly. Type of diet and level of physical activity are now considered important factors affecting prostate health in the aging male. However, whether physical exercise, weight loss, and modifications of dietary habit can really alter the natural history of BPH/LUTS remains to be determined. Further research is advisable to better clarify these points. PMID:24688539

Offline multiple adaptive planning strategy for concurrent irradiation of the prostate and pelvic lymph nodes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qi, Peng; Xia, Ping, E-mail: xiap@ccf.org; Pouliot, Jean

2014-02-15

Purpose: Concurrent irradiation of the prostate and pelvic lymph nodes (PLNs) can be challenging due to the independent motion of the two target volumes. To address this challenge, the authors have proposed a strategy referred to as Multiple Adaptive Planning (MAP). To minimize the number of MAP plans, the authors’ previous work only considered the prostate motion in one major direction. After analyzing the pattern of the prostate motion, the authors investigated a practical number of intensity-modulated radiotherapy (IMRT) plans needed to accommodate the prostate motion in two major directions simultaneously. Methods: Six patients, who received concurrent irradiation of themore » prostate and PLNs, were selected for this study. Nine MAP-IMRT plans were created for each patient with nine prostate contours that represented the prostate at nine locations with respect to the PLNs, including the original prostate contour and eight contours shifted either 5 mm in a single anterior-posterior (A-P), or superior-inferior (S-I) direction, or 5 mm in both A-P and S-I directions simultaneously. From archived megavoltage cone beam CT (MV-CBCT) and a dual imaging registration, 17 MV-CBCTs from 33 available MV-CBCT from these patients showed large prostate displacements (>3 mm in any direction) with respect to the pelvic bones. For each of these 17 fractions, one of nine MAP-IMRT plans was retrospectively selected and applied to the MV-CBCT for dose calculation. For comparison, a simulated isocenter-shifting plan and a reoptimized plan were also created for each of these 17 fractions. The doses to 95% (D95) of the prostate and PLNs, and the doses to 5% (D5) of the rectum and bladder were calculated and analyzed. Results: For the prostate, D95 > 97% of the prescription dose was observed in 16, 16, and 17 of 17 fractions for the MAP, isocenter-shifted, and reoptimized plans, respectively. For PLNs, D95 > 97% of the prescription doses was observed in 10, 3, and 17 of 17 fractions for the three types of verification plans, respectively. The D5 (mean ± SD) of the rectum was 45.78 ± 5.75, 45.44 ± 4.64, and 44.64 ± 2.71 Gy, and the D5 (mean ± SD) of the bladder was 45.18 ± 2.70, 46.91 ± 3.04, and 45.67 ± 3.61 Gy for three types of verification plans, respectively. Conclusions: The MAP strategy with nine IMRT plans to accommodate the prostate motions in two major directions achieved good dose coverage to the prostate and PLNs. The MAP approach can be immediately used in clinical practice without requiring extra hardware and software.« less

SU-E-J-221: A Novel Expansion Method for MRI Based Target Delineation in Prostate Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ruiz, B; East Carolina University, Greenville, NC; Feng, Y

Purpose: To compare a novel bladder/rectum carveout expansion method on MRI delineated prostate to standard CT and expansion based methods for maintaining prostate coverage while providing superior bladder and rectal sparing. Methods: Ten prostate cases were planned to include four trials: MRI vs CT delineated prostate/proximal seminal vesicles, and each image modality compared to both standard expansions (8mm 3D expansion and 5mm posterior, i.e. ∼8mm) and carveout method expansions (5mm 3D expansion, 4mm posterior for GTV-CTV excluding expansion into bladder/rectum followed by additional 5mm 3D expansion to PTV, i.e. ∼1cm). All trials were planned to total dose 7920 cGy viamore » IMRT. Evaluation and comparison was made using the following criteria: QUANTEC constraints for bladder/rectum including analysis of low dose regions, changes in PTV volume, total control points, and maximum hot spot. Results: ∼8mm MRI expansion consistently produced the most optimal plan with lowest total control points and best bladder/rectum sparing. However, this scheme had the smallest prostate (average 22.9% reduction) and subsequent PTV volume, consistent with prior literature. ∼1cm MRI had an average PTV volume comparable to ∼8mm CT at 3.79% difference. Bladder QUANTEC constraints were on average less for the ∼1cm MRI as compared to the ∼8mm CT and observed as statistically significant with 2.64% reduction in V65. Rectal constraints appeared to follow the same trend. Case-by-case analysis showed variation in rectal V30 with MRI delineated prostate being most favorable regardless of expansion type. ∼1cm MRI and ∼8mm CT had comparable plan quality. Conclusion: MRI delineated prostate with standard expansions had the smallest PTV leading to margins that may be too tight. Bladder/rectum carveout expansion method on MRI delineated prostate was found to be superior to standard CT based methods in terms of bladder and rectal sparing while maintaining prostate coverage. Continued investigation is warranted for further validation.« less

Comprehensive Evaluation of Programmed Death-Ligand 1 Expression in Primary and Metastatic Prostate Cancer.

PubMed

Haffner, Michael C; Guner, Gunes; Taheri, Diana; Netto, George J; Palsgrove, Doreen N; Zheng, Qizhi; Guedes, Liana Benevides; Kim, Kunhwa; Tsai, Harrison; Esopi, David M; Lotan, Tamara L; Sharma, Rajni; Meeker, Alan K; Chinnaiyan, Arul M; Nelson, William G; Yegnasubramanian, Srinivasan; Luo, Jun; Mehra, Rohit; Antonarakis, Emmanuel S; Drake, Charles G; De Marzo, Angelo M

2018-06-01

Antibodies targeting the programmed cell death protein 1/programmed death-ligand 1 (PD-L1) interaction have shown clinical activity in multiple cancer types. PD-L1 protein expression is a clinically validated predictive biomarker of response for such therapies. Prior studies evaluating the expression of PD-L1 in primary prostate cancers have reported highly variable rates of PD-L1 positivity. In addition, limited data exist on PD-L1 expression in metastatic castrate-resistant prostate cancer (mCRPC). Here, we determined PD-L1 protein expression by immunohistochemistry using a validated PD-L1-specific antibody (SP263) in a large and representative cohort of primary prostate cancers and prostate cancer metastases. The study included 539 primary prostate cancers comprising 508 acinar adenocarcinomas, 24 prostatic duct adenocarcinomas, 7 small-cell carcinomas, and a total of 57 cases of mCRPC. PD-L1 positivity was low in primary acinar adenocarcinoma, with only 7.7% of cases showing detectable PD-L1 staining. Increased levels of PD-L1 expression were noted in 42.9% of small-cell carcinomas. In mCRPC, 31.6% of cases showed PD-L1-specific immunoreactivity. In conclusion, in this comprehensive evaluation of PD-L1 expression in prostate cancer, PD-L1 expression is rare in primary prostate cancers, but increased rates of PD-L1 positivity were observed in mCRPC. These results will be important for the future clinical development of programmed cell death protein 1/PD-L1-targeting therapies in prostate cancer. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Are blood group isoantigens lost from malignant prostatic epithelium? Immunohistochemical support for the preservation of the H isoantigen.

PubMed Central

Vowden, P.; Lowe, A. D.; Lennox, E. S.; Bleehen, N. M.

1986-01-01

Previous studies while demonstrating the presence of blood group isoantigens on normal prostatic epithelium have failed to identify such antigens on malignant prostatic tissue. Using a series of blood group specific monoclonal antibodies directed towards the A, B, H and Y antigens we have reinvestigated blood group isoantigen expression in both benign prostatic hypertrophy and prostatic adenocarcinoma. Results obtained from areas of benign prostatic hypertrophy are in broad agreement with those published however though we were unable to detect either A or B blood group isoantigens Type 2H and Y isoantigens were identified in 10 of the 12 tumours. These findings, while differing from previously reported results, lend support to the suggested connection between ontogenesis, oncogenesis and blood group isoantigen expression and also support the proposed link between Type 2 structures and malignant transformation. Images Figure 1 Figure 2 PMID:2421753

An endocrine pathway in the prostate, ERβ, AR, 5α-androstane-3β,17β-diol, and CYP7B1, regulates prostate growth

PubMed Central

Weihua, Zhang; Lathe, Richard; Warner, Margaret; Gustafsson, Jan-Åke

2002-01-01

Epithelial proliferation of the ventral prostate in rodents peaks between 2 and 4 weeks of age, and by week 8, proliferating cells are rare. We have used ERβ−/− and CYP7B1−/− mice to investigate the role of ERβ and one of its ligands, 5α-androstane-3β,17β-diol (3βAdiol), in growth of the ventral prostate. Before puberty, ERβ was found in quiescent but not in proliferating cells, and proliferating cells occurred more frequently in ventral prostates of ERβ−/− mice than in wild-type littermates. Treatment with 3βAdiol decreased proliferation in wild-type but not in ERβ−/− mice. In rats, treatment with 3βAdiol from postnatal day 2 to 28 resulted in reduction in growth of ventral prostates. The prostates of CYP7B1−/− mice were hypoproliferative before puberty and smaller than those of their wild-type littermates after puberty. Because CYP7B1 represents the major pathway for inactivating 3βAdiol in the prostate, we suggest that ERβ, 3βAdiol, and CYP7B1 are the components of a pathway that regulates growth of the rodent ventral prostate. In this pathway, ERβ is an antiproliferative receptor, 3βAdiol is an ERβ ligand, and CYP7B1 is the enzyme that regulates ERβ function by regulating the level of 3βAdiol. PMID:12370428

Effects of the flavonoid drug quercetin on the response of human prostate tumours to hyperthermia in vitro and in vivo.

PubMed

Asea, A; Ara, G; Teicher, B A; Stevenson, M A; Calderwood, S K

2001-01-01

Tumour hyperthermia, although potentially a powerful therapeutic agent and radiation sensitizer, is hindered by a number of considerations including inhomogeneous heating of deep seated tumours due to energy deposition and perfusion issues. One solution is to design hyperthermia sensitizers to amplify the effects of hyperthermia, particularly at cold spots within the tumour undergoing treatment. This study examined the use of Quercetin, a flavonoid drug shown previously to antagonize the expression of HSP72 and induce apoptosis as a sensitizer of prostate cancer growth in vivo. Quercetin dose-dependently suppressed PC-3 tumour growth in vitro and in vivo. When combined in a treatment protocol with hyperthermia, quercetin drastically inhibited tumour growth and potently amplified the effects of hyperthermia on two prostate tumour types, PC-3 and DU-145 in vivo. These experiments, thus, suggest the use of Quercetin as a hyperthermia sensitizer in the treatment of prostate carcinoma.

A polymorphism in the glucokinase gene that raises plasma fasting glucose, rs1799884, is associated with diabetes mellitus and prostate cancer: findings from a population-based, case-control study (the ProtecT study)

PubMed Central

Murad, Ali S; Smith, George Davey; Lewis, Sarah J; Cox, Angela; Donovan, Jenny L; Neal, David E; Hamdy, Freddie C; Martin, Richard M

2010-01-01

Epidemiological studies have identified a positive association between prostate cancer and recent onset type 2 diabetes mellitus but an increasingly inverse association with greater duration of type 2 diabetes. The mecha- nisms underlying these paradoxical associations are not clear. A single nucleotide polymorphism in the glucokinase gene, rs1799884, is associated with higher circulating plasma fasting glucose and with an increased risk of type 2 diabetes. We report a case-control study nested within the population-based Prostate testing for cancer and Treatment (ProtecT) study ISRCTN20141297. Men aged 50-69 years based around 9 UK cities were invited for a prostate specific antigen (PSA) test between June 2002 and November 2006. 1,551 cases and 2,993 controls were geno-typed. We observed suggestive evidence for a positive association between the AA variant rs1799884 and PSA-detected prostate cancer (ORAA V GG= 1.40, 95% CI= 0.95 to 2.07). There was little evidence that this effect was greater for more advanced stage/ grade cancers (ORAA V GG= 1.78, 95% CI= 0.99 to 3.21) versus less advanced cancers (ORAA V GG= 1.23, 95% CI= 0.77 to 1.94) (p for interaction = 0.33). The rs1799884 genotype was not associated with PSA concentration, suggesting that any effect on prostate cancer risk is not attributable to PSA detection bias. Our results provide suggestive evidence for a link between a genotype associated with type 2 diabetes mellitus and PSA-detected prostate cancer. We hypothesize that hyperglycaemia may be important in mediating this relationship. PMID:21537389

MicroRNA-145 is regulated by DNA methylation and p53 gene mutation in prostate cancer

PubMed Central

Suh, Seong O.; Chen, Yi; Zaman, Mohd Saif; Hirata, Hiroshi; Yamamura, Soichiro; Shahryari, Varahram; Liu, Jan; Tabatabai, Z.Laura; Kakar, Sanjay; Deng, Guoren; Tanaka, Yuichiro; Dahiya, Rajvir

2011-01-01

MiR-145 is downregulated in various cancers including prostate cancer. However, the underlying mechanisms of miR-145 downregulation are not fully understood. Here, we reported that miR-145 was silenced through DNA hypermethylation and p53 mutation status in laser capture microdissected (LCM) prostate cancer and matched adjacent normal tissues. In 22 of 27 (81%) prostate tissues, miR-145 was significantly downregulated in the cancer compared with the normal tissues. Further studies on miR-145 downregulation mechanism showed that miR-145 is methylated at the promoter region in both prostate cancer tissues and 50 different types of cancer cell lines. In seven cancer cell lines with miR-145 hypermethylation, 5-aza-2′-deoxycytidine treatment dramatically induced miR-145 expression. Interestingly, we also found a significant correlation between miR-145 expression and the status of p53 gene in both LCM prostate tissues and 47 cancer cell lines. In 29 cell lines with mutant p53, miR-145 levels were downregulated in 28 lines (97%), whereas in 18 cell lines with wild-type p53 (WT p53), miR-145 levels were downregulated in only 6 lines (33%, P < 0.001). Electrophoretic mobility shift assay showed that p53 binds to the p53 response element upstream of miR-145, but the binding was inhibited by hypermethylation. To further confirm that p53 binding to miR-145 could regulate miR-145 expression, we transfected WT p53 and MUT p53 into PC-3 cells and found that miR-145 is upregulated by WT p53 but not with MUTp53. The apoptotic cells are increased after WT p53 transfection. In summary, this is the first report documenting that downregulation of miR-145 is through DNA methylation and p53 mutation pathways in prostate cancer. PMID:21349819

CHEK2 mutation and risk of prostate cancer: a systematic review and meta-analysis

PubMed Central

Wang, Yue; Dai, Bo; Ye, Dingwei

2015-01-01

Background: CHEK2 encodes for a G2 checkpoint kinase which plays a critical role in DNA repair. Its mutation confers an increased risk of breast cancer. It has also been suggested to increase risks of prostate cancer, but its involvement with this type of cancer has not been confirmed. Methods: We performed a systematic review and meta-analysis to clarify the association between CHEK2 1100delC, IVS2+1G>A, I157T mutation and risk of Prostate Cancer. A comprehensive, computerized literature search of PubMed until December 27, 2014 was carried out. Eligible studies were included according to specific inclusion criteria. Pooled hazard ratio was estimated using the fixed effects model or random effects model according to heterogeneity between studies. Results: Eight eligible studies were included in the analysis, all were retrospective studies. The overall meta-analysis demonstrated that the CHEK2 1100delC mutation (OR 3.29; 95% confidence interval: 1.85-5.85; P = 0.00) and I157T missense mutation (OR 1.80; 95% confidence interval: 1.51-2.14; P = 0.00) was associated with higher risk of Prostate Cancer, and CHEK2 1100delC mutation is irrelevant to familial aggregation phenomenon of prostate cancer (OR 1.59; 95% confidence interval: 0.79-3.20; P = 0.20). The IVS2+1G>A mutation is also irrelevant to Prostate Cancer (OR = 1.59, 95% CI = 0.93-2.71, P = 0.09). None of the single studies materially altered the original results and no evidence of publication bias was found. Conclusion: CHEK2 1100delC mutation and I157T missense mutation in males indicates higher risk of Prostate Cancer, but there’s no evidence to prove the CHEK2 1100delC mutation was associated with Familial prostate cancer. PMID:26629066

CHEK2 mutation and risk of prostate cancer: a systematic review and meta-analysis.

PubMed

Wang, Yue; Dai, Bo; Ye, Dingwei

2015-01-01

CHEK2 encodes for a G2 checkpoint kinase which plays a critical role in DNA repair. Its mutation confers an increased risk of breast cancer. It has also been suggested to increase risks of prostate cancer, but its involvement with this type of cancer has not been confirmed. We performed a systematic review and meta-analysis to clarify the association between CHEK2 1100delC, IVS2+1G>A, I157T mutation and risk of Prostate Cancer. A comprehensive, computerized literature search of PubMed until December 27, 2014 was carried out. Eligible studies were included according to specific inclusion criteria. Pooled hazard ratio was estimated using the fixed effects model or random effects model according to heterogeneity between studies. Eight eligible studies were included in the analysis, all were retrospective studies. The overall meta-analysis demonstrated that the CHEK2 1100delC mutation (OR 3.29; 95% confidence interval: 1.85-5.85; P = 0.00) and I157T missense mutation (OR 1.80; 95% confidence interval: 1.51-2.14; P = 0.00) was associated with higher risk of Prostate Cancer, and CHEK2 1100delC mutation is irrelevant to familial aggregation phenomenon of prostate cancer (OR 1.59; 95% confidence interval: 0.79-3.20; P = 0.20). The IVS2+1G>A mutation is also irrelevant to Prostate Cancer (OR = 1.59, 95% CI = 0.93-2.71, P = 0.09). None of the single studies materially altered the original results and no evidence of publication bias was found. CHEK2 1100delC mutation and I157T missense mutation in males indicates higher risk of Prostate Cancer, but there's no evidence to prove the CHEK2 1100delC mutation was associated with Familial prostate cancer.

Gap junctional communication in the male reproductive system.

PubMed

Pointis, Georges; Fiorini, Céline; Defamie, Norah; Segretain, Dominique

2005-12-20

Male fertility is a highly controlled process that allows proliferation, meiosis and differentiation of male germ cells in the testis, final maturation in the epididymis and also requires functional male accessory glands: seminal vesicles, prostate and corpus cavernosum. In addition to classical endocrine and paracrine controls, mainly by gonadotropins LH and FSH and steroids, there is now strong evidence that all these processes are dependent upon the presence of homocellular or heterocellular junctions, including gap junctions and their specific connexins (Cxs), between the different cell types that structure the male reproductive tract. The present review is focused on the identification of Cxs, their distribution in the testis and in different structures of the male genital tract (epididymis, seminal vesicle, prostate, corpus cavernosum), their crucial role in the control of spermatogenesis and their implication in the function of the male accessory glands, including functional smooth muscle tone. Their potential dysfunctions in some testis (spermatogenic arrest, seminoma) and prostate (benign hyperplasia, adenocarcinoma) diseases and in the physiopathology of the human erectile function are also discussed.

Correlation of mRNA and protein levels: Cell type-specific gene expression of cluster designation antigens in the prostate

PubMed Central

Pascal, Laura E; True, Lawrence D; Campbell, David S; Deutsch, Eric W; Risk, Michael; Coleman, Ilsa M; Eichner, Lillian J; Nelson, Peter S; Liu, Alvin Y

2008-01-01

Background: Expression levels of mRNA and protein by cell types exhibit a range of correlations for different genes. In this study, we compared levels of mRNA abundance for several cluster designation (CD) genes determined by gene arrays using magnetic sorted and laser-capture microdissected human prostate cells with levels of expression of the respective CD proteins determined by immunohistochemical staining in the major cell types of the prostate – basal epithelial, luminal epithelial, stromal fibromuscular, and endothelial – and for prostate precursor/stem cells and prostate carcinoma cells. Immunohistochemical stains of prostate tissues from more than 50 patients were scored for informative CD antigen expression and compared with cell-type specific transcriptomes. Results: Concordance between gene and protein expression findings based on 'present' vs. 'absent' calls ranged from 46 to 68%. Correlation of expression levels was poor to moderate (Pearson correlations ranged from 0 to 0.63). Divergence between the two data types was most frequently seen for genes whose array signals exceeded background (> 50) but lacked immunoreactivity by immunostaining. This could be due to multiple factors, e.g. low levels of protein expression, technological sensitivities, sample processing, probe set definition or anatomical origin of tissue and actual biological differences between transcript and protein abundance. Conclusion: Agreement between these two very different methodologies has great implications for their respective use in both molecular studies and clinical trials employing molecular biomarkers. PMID:18501003

Prostate organogenesis: tissue induction, hormonal regulation and cell type specification

PubMed Central

Toivanen, Roxanne

2017-01-01

Prostate organogenesis is a complex process that is primarily mediated by the presence of androgens and subsequent mesenchyme-epithelial interactions. The investigation of prostate development is partly driven by its potential relevance to prostate cancer, in particular the apparent re-awakening of key developmental programs that occur during tumorigenesis. However, our current knowledge of the mechanisms that drive prostate organogenesis is far from complete. Here, we provide a comprehensive overview of prostate development, focusing on recent findings regarding sexual dimorphism, bud induction, branching morphogenesis and cellular differentiation. PMID:28400434

Acute progressive paravascular placoid neuroretinopathy with negative-type electroretinography in paraneoplastic retinopathy.

PubMed

Chen, Fred K; Chew, Avenell L; Zhang, Dan; Chen, Shang-Chih; Chelva, Enid; Chandrasekera, Erandi; Koay, Eleanor M H; Forrester, John; McLenachan, Samuel

2017-06-01

Paraneoplastic retinopathy can be the first manifestation of systemic malignancy. A subset of paraneoplastic retinopathy is characterized by negative-type electroretinography (ERG) without fundus abnormality. Here we describe the multimodal imaging and clinico-pathological correlation of a unique case of acute progressive paravascular placoid neuroretinopathy with suspected retinal depolarizing bipolar cell dysfunction preceding the diagnosis of metastatic small cell carcinoma of the prostate. ERG was performed according to the International Society for Clinical Electrophysiology of Vision standards. Imaging modalities included near-infrared reflectance, blue-light autofluorescence, fluorescein and indocyanine green angiographies, spectral domain optical coherence tomography, ultra-widefield colour and green-light autofluorescence imaging, microperimetry and adaptive optics imaging. Patient serum was screened for anti-retinal antibodies using western blotting. Immunostaining and histological analyses were performed on sections from human retinal tissues and a patient prostate biopsy. Serial multimodal retinal imaging, microperimetry and adaptive optics photography demonstrated a paravascular distribution of placoid lesions characterized by hyper-reflectivity within the outer nuclear layer resembling type 2 acute macular neuroretinopathy. There was no visible lesion within the inner nuclear layer despite electronegative-type ERG. Six months later, the patient presented with metastatic small cell carcinoma of the prostate. Tumour cells were immunopositive for glyceraldehyde-3-phosphate dehydrogenase, enolase and recoverin as well as neuroendocrine markers. The patient's serum reacted to cytoplasmic and nuclear antigens in the prostate biopsy and in human retina. Anti-retinal antibodies against several antigens were detected by both commercial and in-house western blots. A spectrum of autoreactive anti-retinal antibodies is associated with a unique phenotype of acute progressive paravascular placoid neuroretinopathy resulting in degeneration of photoreceptor cells, inner retinal dysfunction and classic electronegative ERG in paraneoplastic retinopathy. Detailed clinical, functional and immunological phenotyping of paraneoplastic retinopathy illustrated the complex mechanism of paraneoplastic syndrome.

EAU guidelines on the treatment and follow-up of non-neurogenic male lower urinary tract symptoms including benign prostatic obstruction.

PubMed

Oelke, Matthias; Bachmann, Alexander; Descazeaud, Aurélien; Emberton, Mark; Gravas, Stavros; Michel, Martin C; N'dow, James; Nordling, Jørgen; de la Rosette, Jean J

2013-07-01

To present a summary of the 2013 version of the European Association of Urology guidelines on the treatment and follow-up of male lower urinary tract symptoms (LUTS). We conducted a literature search in computer databases for relevant articles published between 1966 and 31 October 2012. The Oxford classification system (2001) was used to determine the level of evidence for each article and to assign the grade of recommendation for each treatment modality. Men with mild symptoms are suitable for watchful waiting. All men with bothersome LUTS should be offered lifestyle advice prior to or concurrent with any treatment. Men with bothersome moderate-to-severe LUTS quickly benefit from α1-blockers. Men with enlarged prostates, especially those >40ml, profit from 5α-reductase inhibitors (5-ARIs) that slowly reduce LUTS and the probability of urinary retention or the need for surgery. Antimuscarinics might be considered for patients who have predominant bladder storage symptoms. The phosphodiesterase type 5 inhibitor tadalafil can quickly reduce LUTS to a similar extent as α1-blockers, and it also improves erectile dysfunction. Desmopressin can be used in men with nocturia due to nocturnal polyuria. Treatment with an α1-blocker and 5-ARI (in men with enlarged prostates) or antimuscarinics (with persistent storage symptoms) combines the positive effects of either drug class to achieve greater efficacy. Prostate surgery is indicated in men with absolute indications or drug treatment-resistant LUTS due to benign prostatic obstruction. Transurethral resection of the prostate (TURP) is the current standard operation for men with prostates 30-80ml, whereas open surgery or transurethral holmium laser enucleation is appropriate for men with prostates >80ml. Alternatives for monopolar TURP include bipolar TURP and transurethral incision of the prostate (for glands <30ml) and laser treatments. Transurethral microwave therapy and transurethral needle ablation are effective minimally invasive treatments with higher retreatment rates compared with TURP. Prostate stents are an alternative to catheterisation for men unfit for surgery. Ethanol or botulinum toxin injections into the prostate are still experimental. These symptom-oriented guidelines provide practical guidance for the management of men experiencing LUTS. The full version is available online (www.uroweb.org/gls/pdf/12_Male_LUTS.pdf). Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Evidence that insulin-like growth factor I and growth hormone are required for prostate gland development.

PubMed

Ruan, W; Powell-Braxton, L; Kopchick, J J; Kleinberg, D L

1999-05-01

Insulin-like growth factor I (IGF-I) has been implicated as a factor that may predispose one to prostate cancer. However, no specific relationship between IGF-I and prostate development or cancer in vivo has been established. To determine whether IGF-I was important in prostate development, we examined prostate architecture in IGF-I(-/-) null mice and wild-type littermates. Glands from 44-day-old IGF-I-deficient animals were not only smaller than those from wild-type mice, but also had fewer terminal duct tips and branch points and deficits in tertiary and quaternary branching (P < 0.0001), indicating a specific impairment in gland structure. Administration of des(1-3)-IGF-I for 7 days partially reversed the deficit by increasing those parameters of prostate development (P < 0.006). That IGF-I production probably mediates an effect of GH in this process was indicated by the observations that GH antagonist transgenic mice also had significantly impaired prostate development (P < 0.0002) and that bovine GH had no independent effect on stimulating prostate development in IGF-I null animals. The data indicate that IGF-I deficiency is the proximate cause of impaired prostate development and give credence to the idea that, like testosterone, GH and IGF-I may be involved in prostate cancer growth as an extension of a normal process.

Tuberculous prostatitis: mimicking a cancer.

PubMed

Aziz, El Majdoub; Abdelhak, Khallouk; Hassan, Farih Moulay

2016-01-01

Genitourinary tuberculosis is a common type of extra-pulmonary tuberculosis . The kidneys, ureter, bladder or genital organs are usually involved. Tuberculosis of the prostate has mainly been described in immune-compromised patients. However, it can exceptionally be found as an isolated lesion in immune-competent patients. Tuberculosis of the prostate may be difficult to differentiate from carcinoma of the prostate and the chronic prostatitis when the prostate is hard and nodular on digital rectal examination and the urine is negative for tuberculosis bacilli. In many cases, a diagnosis of tuberculous prostatitis is made by the pathologist, or the disease is found incidentally after transurethral resection. Therefore, suspicion of tuberculous prostatitis requires a confirmatory biopsy of the prostate. We report the case of 60-year-old man who presented a low urinary tract syndrome. After clinical and biological examination, and imaging, prostate cancer was highly suspected. Transrectal needle biopsy of the prostate was performed and histological examination showed tuberculosis lesions.

Bacterial prostatitis.

PubMed

Gill, Bradley C; Shoskes, Daniel A

2016-02-01

The review provides the infectious disease community with a urologic perspective on bacterial prostatitis. Specifically, the article briefly reviews the categorization of prostatitis by type and provides a distillation of new findings published on bacterial prostatitis over the past year. It also highlights key points from the established literature. Cross-sectional prostate imaging is becoming more common and may lead to more incidental diagnoses of acute bacterial prostatitis. As drug resistance remains problematic in this condition, the reemergence of older antibiotics such as fosfomycin, has proven beneficial. With regard to chronic bacterial prostatitis, no clear clinical risk factors emerged in a large epidemiological study. However, bacterial biofilm formation has been associated with more severe cases. Surgery has a limited role in bacterial prostatitis and should be reserved for draining of a prostatic abscess or the removal of infected prostatic stones. Prostatitis remains a common and bothersome clinical condition. Antibiotic therapy remains the basis of treatment for both acute and chronic bacterial prostatitis. Further research into improving prostatitis treatment is indicated.

Expression of membrane-type 1 matrix metalloproteinase (MT1-MMP) on prostate cancer cell lines.

PubMed

Nagakawa, O; Murakami, K; Yamaura, T; Fujiuchi, Y; Murata, J; Fuse, H; Saiki, I

2000-07-31

Membrane-type metalloproteinase-1 (MT1-MMP) is a transmembrane metalloproteinase, which activates proMMP-2 and expressed on the cell surface in many invasive cancer cells. We investigated the expression of MT1-MMP in prostate cancer cell lines. MT1-MMP protein and mRNA were expressed in PC-3, DU-145 and TSU-pr1 cells (androgen-independent prostate cancer cell lines), but in LNCaP cells (androgen-dependent prostate cancer cell line). MT1-MMP protein was negative and mRNA was low to detect by RT-PCR. Cell lysate of PC-3 cleaved proMMP-2 to the active form. In addition, both hepatocyte growth factor (HGF) and gastrin-releasing peptide (GRP) increased Matrigel invasion and induced the expression of MT1-MMP protein in DU-145 prostate cancer cells. These results suggest that MT1-MMP is indeed the tumor-specific activator of proMMP-2 in androgen-independent prostate cancer cells and plays an important role in the invasive properties of prostate cancer cells.

Cadherin Switching and Activation of β-Catenin Signaling Underlie Proinvasive Actions of Calcitonin-Calcitonin Receptor Axis in Prostate Cancer*S⃞

PubMed Central

Shah, Girish V.; Muralidharan, Anbalagan; Gokulgandhi, Mitan; Soan, Kamal; Thomas, Shibu

2009-01-01

Calcitonin, a neuroendocrine peptide, and its receptor are localized in the basal epithelium of benign prostate but in the secretory epithelium of malignant prostates. The abundance of calcitonin and calcitonin receptor mRNA displays positive correlation with the Gleason grade of primary prostate cancers. Moreover, calcitonin increases tumorigenicity and invasiveness of multiple prostate cancer cell lines by cyclic AMP-dependent protein kinase-mediated actions. These actions include increased secretion of matrix metalloproteinases and urokinase-type plasminogen activator and an increase in prostate cancer cell invasion. Activation of calcitonin-calcitonin receptor autocrine loop in prostate cancer cell lines led to the loss of cell-cell adhesion, destabilization of tight and adherens junctions, and internalization of key integral membrane proteins. In addition, the activation of calcitonin-calcitonin receptor axis induced epithelial-mesenchymal transition of prostate cancer cells as characterized by cadherin switch and the expression of the mesenchymal marker, vimentin. The activated calcitonin receptor phosphorylated glycogen synthase kinase-3, a key regulator of cytosolic β-catenin degradation within the WNT signaling pathway. This resulted in the accumulation of intracellular β-catenin, its translocation in the nucleus, and transactivation of β-catenin-responsive genes. These results for the first time identify actions of calcitonin-calcitonin receptor axis on prostate cancer cells that lead to the destabilization of cell-cell junctions, epithelial-to-mesenchymal transition, and activation of WNT/β-catenin signaling. The results also suggest that cyclic AMP-dependent protein kinase plays a key role in calcitonin receptor-induced destabilization of cell-cell junctions and activation of WNT-β-catenin signaling. PMID:19001380

Melatonin Decreases Glucose Metabolism in Prostate Cancer Cells: A 13C Stable Isotope-Resolved Metabolomic Study.

PubMed

Hevia, David; Gonzalez-Menendez, Pedro; Fernandez-Fernandez, Mario; Cueto, Sergio; Rodriguez-Gonzalez, Pablo; Garcia-Alonso, Jose I; Mayo, Juan C; Sainz, Rosa M

2017-07-26

The pineal neuroindole melatonin exerts an exceptional variety of systemic functions. Some of them are exerted through its specific membrane receptors type 1 and type 2 (MT1 and MT2) while others are mediated by receptor-independent mechanisms. A potential transport of melatonin through facilitative glucose transporters (GLUT/ SLC2A ) was proposed in prostate cancer cells. The prostate cells have a particular metabolism that changes during tumor progression. During the first steps of carcinogenesis, oxidative phosphorylation is reactivated while the switch to the "Warburg effect" only occurs in advanced tumors and in the metastatic stage. Here, we investigated whether melatonin might change prostate cancer cell metabolism. To do so, 13 C stable isotope-resolved metabolomics in androgen sensitive LNCaP and insensitive PC-3 prostate cancer cells were employed. In addition to metabolite 13 C-labeling, ATP/AMP levels, and lactate dehydrogenase or pentose phosphate pathway activity were measured. Melatonin reduces lactate labeling in androgen-sensitive cells and it also lowers 13 C-labeling of tricarboxylic acid cycle metabolites and ATP production. In addition, melatonin reduces lactate 13 C-labeling in androgen insensitive prostate cancer cells. Results demonstrated that melatonin limits glycolysis as well as the tricarboxylic acid cycle and pentose phosphate pathway in prostate cancer cells, suggesting that the reduction of glucose uptake is a major target of the indole in this tumor type.

How to Study Basement Membrane Stiffness as a Biophysical Trigger in Prostate Cancer and Other Age-related Pathologies or Metabolic Diseases

PubMed Central

Rodriguez-Teja, Mercedes; Breit, Claudia; Clarke, Mitchell; Talar, Kamil; Wang, Kai; Mohammad, Mohammad A.; Pickwell, Sage; Etchandy, Guillermina; Stasiuk, Graeme J.; Sturge, Justin

2016-01-01

Here we describe a protocol that can be used to study the biophysical microenvironment related to increased thickness and stiffness of the basement membrane (BM) during age-related pathologies and metabolic disorders (e.g. cancer, diabetes, microvascular disease, retinopathy, nephropathy and neuropathy). The premise of the model is non-enzymatic crosslinking of reconstituted BM (rBM) matrix by treatment with glycolaldehyde (GLA) to promote advanced glycation endproduct (AGE) generation via the Maillard reaction. Examples of laboratory techniques that can be used to confirm AGE generation, non-enzymatic crosslinking and increased stiffness in GLA treated rBM are outlined. These include preparation of native rBM (treated with phosphate-buffered saline, PBS) and stiff rBM (treated with GLA) for determination of: its AGE content by photometric analysis and immunofluorescent microscopy, its non-enzymatic crosslinking by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE) as well as confocal microscopy, and its increased stiffness using rheometry. The procedure described here can be used to increase the rigidity (elastic moduli, E) of rBM up to 3.2-fold, consistent with measurements made in healthy versus diseased human prostate tissue. To recreate the biophysical microenvironment associated with the aging and diseased prostate gland three prostate cell types were introduced on to native rBM and stiff rBM: RWPE-1, prostate epithelial cells (PECs) derived from a normal prostate gland; BPH-1, PECs derived from a prostate gland affected by benign prostatic hyperplasia (BPH); and PC3, metastatic cells derived from a secondary bone tumor originating from prostate cancer. Multiple parameters can be measured, including the size, shape and invasive characteristics of the 3D glandular acini formed by RWPE-1 and BPH-1 on native versus stiff rBM, and average cell length, migratory velocity and persistence of cell movement of 3D spheroids formed by PC3 cells under the same conditions. Cell signaling pathways and the subcellular localization of proteins can also be assessed. PMID:27684203

Alterations in gene expression profiles during prostate cancer progression: functional correlations to tumorigenicity and down-regulation of selenoprotein-P in mouse and human tumors.

PubMed

Calvo, Alfonso; Xiao, Nianqing; Kang, Jason; Best, Carolyn J M; Leiva, Isabel; Emmert-Buck, Michael R; Jorcyk, Cheryl; Green, Jeffrey E

2002-09-15

To identify molecular changes that occur during prostate tumor progression, we have characterized a series of prostate cancer cell lines isolated at different stages of tumorigenesis from C3(1)/Tag transgenic mice. Cell lines derived from low- and high-grade prostatic intraepithelial neoplasia, invasive carcinoma, and a lung metastasis exhibited significant differences in cell growth, tumorigenicity, invasiveness, and angiogenesis. cDNA microarray analysis of 8700 features revealed correlations between the tumorigenicity of the C3(1)/Tag-Pr cells and changes in the expression levels of genes regulating cell growth, angiogenesis, and invasion. Many changes observed in transcriptional regulation in this in vitro system are similar to those reported for human prostate cancer, as well as other types of human tumors. This analysis of expression patterns has also identified novel genes that may be involved in mechanisms of prostate oncogenesis or serve as potential biomarkers or therapeutic targets for prostate cancer. Examples include the L1-cell adhesion molecule, metastasis-associated gene (MTA-2), Rab-25, tumor-associated signal transducer-2 (Trop-2), and Selenoprotein-P, a gene that binds selenium and prevents oxidative stress. Many genes identified in the Pr-cell line model have been shown to be altered in human prostate cancer. The comprehensive microarray data provides a rational basis for using this model system for studies where alterations of specific genes or pathways are of particular interest. Quantitative real-time reverse transcription-PCR for Selenoprotein-P demonstrated a similar down-regulation of the transcript of this gene in a subset of human prostate tumors, mouse tumors, and prostate carcinoma cell lines. This work demonstrates that expression profiling in animal models may lead to the identification of novel genes involved in human prostate cancer biology.

Expression between African American and Caucasian Prostate Cancer Tissue Reveals that Stroma is the Site of Aggressive Changes

PubMed Central

Kinseth, Matthew A.; Jia, Zhenyu; Rahmatpanah, Farahnaz; Sawyers, Anne; Sutton, Manuel; Wang-Rodriguez, Jessica; Mercola, Dan; McGuire, Kathleen L.

2013-01-01

In prostate cancer, race/ethnicity is the highest risk factor after adjusting for age. African Americans have more aggressive tumors at every clinical stage of the disease, resulting in poorer prognosis and increased mortality. A major barrier to identifying crucial gene activity differences is heterogeneity, including tissue composition variation intrinsic to the histology of prostate cancer. We hypothesized differences in gene expression in specific tissue types would reveal mechanisms involved in the racial disparities of prostate cancer. We examined seventeen pairs of arrays for African Americans and Caucasians that were formed by closely matching the samples based on the known tissue type composition of the tumors. Using pair wise T-test we found significantly altered gene expression between African Americans and Caucasians. Independently, we performed multiple linear regression analyses to associate gene expression with race considering variation in percent tumor and stroma tissue. The majority of differentially expressed genes were associated with tumor-adjacent stroma rather than tumor tissue. Extracellular matrix, Integrin family and signaling mediators of the epithelial-to-mesenchymal transition pathways were all down regulated in stroma of African Americans. Using MetaCore (GeneGo Inc.) analysis, we observed that 35% of significant (p < 10-3) pathways identified EMT and 25% identified immune response pathways especially for Interleukins -2, -4, -5, -6, -7, -10, -13, -15 and -22 as the major changes. Our studies reveal that altered immune and EMT processes in tumor-adjacent stroma may be responsible for the aggressive nature of prostate cancer in African Americans. PMID:23754304

Senescence-Induced Alterations in the Laminin Component of Prostate Epithelial Extracellular Matrix Regulate Progression of Prostate Cancer

DTIC Science & Technology

2009-01-01

Sente B, Dombrowicz D , de Leval J, Closset J, Hennen G (1993) Benign prostatic hyperplasia and normal prostate aging: differences in types I and II 5...influence angiogenesis. J Biol Chem 278: 37849 – 37857 Stuelten CH , DaCosta Byfield S, Arany PR, Karpova TS , Stetler-Stevenson WG, Roberts AB (2005...cancer progression and angiogenesis, the results of these future studies may lead to potential new therapies for prostate cancer. REFERENCES: 1. McNeel D

A new serially transplantable human prostatic cancer (HONDA) in nude mice.

PubMed

Ito, Y Z; Nakazato, Y

1984-08-01

A new serially transplantable human prostatic cancer (HONDA) in nude mice was established from a patient with metastatic prostate carcinoma. The tumor grows well in male nude mice. Doubling time of the tumor weight at passage #13 was 9.5 +/- 0.87 days (mean +/- SD). The tumor retains the original histological features of adenocarcinoma even after 6 years of continuous passage. High levels of human prostatic acid phosphatase were detected by radioimmunoassay in sera from the tumor-bearing mice. The tumor cells contain human prostate specific antigen. Electron microscopy showed particles resembling type A retroviruses in cisterns of endoplasmic reticulum, and particles resembling type C retroviruses in the intercellular space of the tumor cells. The tumor grew well in female mice treated with testosterone, but not in untreated female mice or castrated male mice.

Immunological Mechanisms Underlying Chronic Pelvic Pain and Prostate Inflammation in Chronic Pelvic Pain Syndrome

PubMed Central

Breser, María L.; Salazar, Florencia C.; Rivero, Viginia E.; Motrich, Rubén D.

2017-01-01

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is the most common urologic morbidity in men younger than 50 years and is characterized by a diverse range of pain and inflammatory symptoms, both in type and severity, that involve the region of the pelvis, perineum, scrotum, rectum, testes, penis, and lower back. In most patients, pain is accompanied by inflammation in the absence of an invading infectious agent. Since CP/CPPS etiology is still not well established, available therapeutic options for patients are far from satisfactory for either physicians or patients. During the past two decades, chronic inflammation has been deeply explored as the cause of CP/CPPS. In this review article, we summarize the current knowledge regarding immunological mechanisms underlying chronic pelvic pain and prostate inflammation in CP/CPPS. Cumulative evidence obtained from both human disease and animal models indicate that several factors may trigger chronic inflammation in the form of autoimmunity against prostate, fostering chronic prostate recruitment of Th1 cells, and different other leukocytes, including mast cells, which might be the main actors in the consequent development of chronic pelvic pain. Thus, the local inflammatory milieu and the secretion of inflammatory mediators may induce neural sensitization leading to chronic pelvic pain development. Although scientific advances are encouraging, additional studies are urgently needed to establish the relationship between prostatitis development, mast cell recruitment to the prostate, and the precise mechanisms by which they would induce pelvic pain. PMID:28824626

High Spatiotemporal Resolution Prostate MRI

DTIC Science & Technology

2016-09-01

1 AD AWARD NUMBER: W81XWH-15-1-0341 TITLE: High Spatiotemporal Resolution Prostate MRI PRINCIPAL INVESTIGATOR: Stephen J. Riederer CONTRACTING...REPORT TYPE Annual 3. DATES COVERED 15 Aug 2015 - 14 Aug 2016 4. TITLE AND SUBTITLE High Spatiotemporal Resolution Prostate MRI 5a. CONTRACT NUMBER...improved means using MRI for detecting prostate cancer with the potential for differentiating disease aggressiveness. The hypothesis is that dynamic

Roswell Park Cancer Institute/ Howard University Prostate Cancer Scholars Program

DTIC Science & Technology

2016-10-01

INVESTIGATOR: Wendy Huss, PhD CONTRACTING ORGANIZATION : Health Research , Inc. Buffalo, NY 14263-0001 REPORT DATE: October 2016 TYPE OF REPORT: Annual...RHPCS Program to encourage interns to enter graduate training and careers in prostate cancer research . Completion dates for activities and progress on... interns to enter graduate training and careers in prostate cancer research . SOW-Major Task 4: Track Prostate Cancer Scholar professional activities

The Patient Burden of Bladder Outlet Obstruction after Prostate Cancer Treatment.

PubMed

Liberman, Daniel; Jarosek, Stephanie; Virnig, Beth A; Chu, Haitao; Elliott, Sean P

2016-05-01

Bladder outlet obstruction after prostate cancer therapy imposes a significant burden on health and quality of life in men. Our objective was to describe the burden of bladder outlet obstruction after prostate cancer therapy by detailing the type of procedures performed and how often those procedures were repeated in men with recurrent bladder outlet obstruction. Using SEER (Surveillance, Epidemiology and End Results)-Medicare linked data from 1992 to 2007 with followup through 2009 we identified 12,676 men who underwent at least 1 bladder outlet obstruction procedure after prostate cancer therapy, including external beam radiotherapy in 3,994, brachytherapy in 1,485, brachytherapy plus external beam radiotherapy in 1,847, radical prostatectomy in 4,736, radical prostatectomy plus external beam radiotherapy in 369 and cryotherapy in 245. Histogram, incidence rates and Cox proportional hazards models with repeat events analysis were done to describe the burden of repeat bladder outlet obstruction treatments stratified by prostate cancer therapy type. We describe the type of bladder outlet obstruction surgery grouped by level of invasiveness. At a median followup of 8.8 years 44.6% of men underwent 2 or more bladder outlet obstruction procedures. Compared to men who underwent radical prostatectomy those treated with brachytherapy and brachytherapy plus external beam radiotherapy were at increased adjusted risk for repeat bladder outlet obstruction treatment (HR 1.2 and 1.32, respectively, each p <0.05). After stricture incision the men treated with radical prostatectomy or radical prostatectomy plus external beam radiotherapy were most likely to undergo dilation at a rate of 34.7% to 35.0%. Stricture resection/ablation was more common after brachytherapy, external beam radiotherapy or brachytherapy plus external beam radiotherapy at a rate of 28.9% to 41.2%. Almost half of the men with bladder outlet obstruction after prostate cancer therapy undergo more than 1 procedure. Furthermore men with bladder outlet obstruction after radiotherapy undergo more invasive endoscopic therapies and are at higher risk for multiple treatments than men with bladder outlet obstruction after radical prostatectomy. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Multilocus sequence typing (MLST) analysis of Propionibacterium acnes isolates from radical prostatectomy specimens.

PubMed

Mak, Tim N; Yu, Shu-Han; De Marzo, Angelo M; Brüggemann, Holger; Sfanos, Karen S

2013-05-01

Inflammation is commonly observed in radical prostatectomy specimens, and evidence suggests that inflammation may contribute to prostate carcinogenesis. Multiple microorganisms have been implicated in serving as a stimulus for prostatic inflammation. The pro-inflammatory anaerobe, Propionibacterium acnes, is ubiquitously found on human skin and is associated with the skin disease acne vulgaris. Recent studies have shown that P. acnes can be detected in prostatectomy specimens by bacterial culture or by culture-independent molecular techniques. Radical prostatectomy tissue samples were obtained from 30 prostate cancer patients and subject to both aerobic and anaerobic culture. Cultured species were identified by 16S rDNA gene sequencing. Propionibacterium acnes isolates were typed using multilocus sequence typing (MLST). Our study confirmed that P. acnes can be readily cultured from prostatectomy tissues (7 of 30 cases, 23%). In some cases, multiple isolates of P. acnes were cultured as well as other Propionibacterium species, such as P. granulosum and P. avidum. Overall, 9 of 30 cases (30%) were positive for Propionibacterium spp. MLST analyses identified eight different sequence types (STs) among prostate-derived P. acnes isolates. These STs belong to two clonal complexes, namely CC36 (type I-2) and CC53/60 (type II), or are CC53/60-related singletons. MLST typing results indicated that prostate-derived P. acnes isolates do not fall within the typical skin/acne STs, but rather are characteristic of STs associated with opportunistic infections and/or urethral flora. The MLST typing results argue against the likelihood that prostatectomy-derived P. acnes isolates represent contamination from skin flora. Copyright © 2012 Wiley Periodicals, Inc.

Innovative and Community-Guided Evaluation and Dissemination of a Prostate Cancer Education Program for African-American Men and Women

PubMed Central

Jackson, Dawnyea D.; Owens, Otis L.; Friedman, Daniela B.; Dubose-Morris, Ragan

2014-01-01

African Americans (AA) are more likely to develop and die from cancer than any other racial or ethnic group. The aims of this research were to: (1) evaluate current education materials being implemented in a community-based prostate cancer education program for AA communities; (2) refine materials based on findings from Aim 1; (3) share updated materials with participants from Aim 1 for additional improvements; and (4) disseminate and evaluate the improved education program through a statewide videoconference with AA men and women. AA individuals evaluated the current education program through a mail survey (n=32) and community forum (n=38). Participants reported that the existing prostate cancer education program content could be understood by lay persons, but recommendations for improvement were identified. They included: defining unknown and/or scientific terminology, increasing readability by increasing font size and enlarging images, and including more recent and relevant statistics. Following refinement of the education materials based on survey and forum feedback, a statewide videoconference was implemented. Following the videoconference, participants (25 men; 3 women) reported that they would encourage others to learn more about prostate cancer, talk to their doctor about whether or not to get screened for prostate cancer, and would recommend the conference to others. There is great potential for using this type of iterative approach to education program development with community and clinical partners for others conducting similar work. PMID:25510370

Prostate cancer epigenetics and its clinical implications

PubMed Central

Yegnasubramanian, Srinivasan

2016-01-01

Normal cells have a level of epigenetic programming that is superimposed on the genetic code to establish and maintain their cell identity and phenotypes. This epigenetic programming can be thought as the architecture, a sort of cityscape, that is built upon the underlying genetic landscape. The epigenetic programming is encoded by a complex set of chemical marks on DNA, on histone proteins in nucleosomes, and by numerous context-specific DNA, RNA, protein interactions that all regulate the structure, organization, and function of the genome in a given cell. It is becoming increasingly evident that abnormalities in both the genetic landscape and epigenetic cityscape can cooperate to drive carcinogenesis and disease progression. Large-scale cancer genome sequencing studies have revealed that mutations in genes encoding the enzymatic machinery for shaping the epigenetic cityscape are among the most common mutations observed in human cancers, including prostate cancer. Interestingly, although the constellation of genetic mutations in a given cancer can be quite heterogeneous from person to person, there are numerous epigenetic alterations that appear to be highly recurrent, and nearly universal in a given cancer type, including in prostate cancer. The highly recurrent nature of these alterations can be exploited for development of biomarkers for cancer detection and risk stratification and as targets for therapeutic intervention. Here, we explore the basic principles of epigenetic processes in normal cells and prostate cancer cells and discuss the potential clinical implications with regards to prostate cancer biomarker development and therapy. PMID:27212125

Prostate cancer epigenetics and its clinical implications.

PubMed

Yegnasubramanian, Srinivasan

2016-01-01

Normal cells have a level of epigenetic programming that is superimposed on the genetic code to establish and maintain their cell identity and phenotypes. This epigenetic programming can be thought as the architecture, a sort of cityscape, that is built upon the underlying genetic landscape. The epigenetic programming is encoded by a complex set of chemical marks on DNA, on histone proteins in nucleosomes, and by numerous context-specific DNA, RNA, protein interactions that all regulate the structure, organization, and function of the genome in a given cell. It is becoming increasingly evident that abnormalities in both the genetic landscape and epigenetic cityscape can cooperate to drive carcinogenesis and disease progression. Large-scale cancer genome sequencing studies have revealed that mutations in genes encoding the enzymatic machinery for shaping the epigenetic cityscape are among the most common mutations observed in human cancers, including prostate cancer. Interestingly, although the constellation of genetic mutations in a given cancer can be quite heterogeneous from person to person, there are numerous epigenetic alterations that appear to be highly recurrent, and nearly universal in a given cancer type, including in prostate cancer. The highly recurrent nature of these alterations can be exploited for development of biomarkers for cancer detection and risk stratification and as targets for therapeutic intervention. Here, we explore the basic principles of epigenetic processes in normal cells and prostate cancer cells and discuss the potential clinical implications with regards to prostate cancer biomarker development and therapy.

Vitamin K and its analogs: Potential avenues for prostate cancer management.

PubMed

Dasari, Subramanyam; Ali, Syed M; Zheng, Guoxing; Chen, Aoshuang; Dontaraju, Venkata Satish; Bosland, Maarten C; Kajdacsy-Balla, Andre; Munirathinam, Gnanasekar

2017-08-22

Epidemiological studies have demonstrated a relationship between cancer incidence and dietary habits. Especially intake of certain essential nutrients like vitamins has been shown to be beneficial in experimental studies and some clinical trials. Vitamin K (VK) is an essential nutrient involved in the blood clotting cascade, and there are considerable experimental data demonstrating its potential anticancer activity in several cancer types including prostate cancer. Previous in vitro and in vivo studies have focused mainly on anti-oxidative effects as the underlying anticancer mechanism of VK. However, recent studies reveal that VK inhibits the growth of cancer cells through other mechanisms, including apoptosis, cell cycle arrest, autophagy, and modulation of various transcription factors such as Myc and Fos. In the present review, we focus on the anticancer effect of dietary VK and its analogs on prostate cancer, with an emphasis on the signaling pathways that are activated following exposure to these compounds. This review also highlights the potential of VK and its derivatives as an adjuvant treatment in combination with other vitamins or with chemotherapeutic drugs. Based on our recent results and a review of the existing literature, we present evidence that VK and its derivatives can potentially be explored as cancer therapy, especially for prostate cancer.

Vitamin K and its analogs: Potential avenues for prostate cancer management

PubMed Central

Dasari, Subramanyam; Ali, Syed M.; Zheng, Guoxing; Chen, Aoshuang; Dontaraju, Venkata Satish; Bosland, Maarten C.; Kajdacsy-Balla, Andre; Munirathinam, Gnanasekar

2017-01-01

Epidemiological studies have demonstrated a relationship between cancer incidence and dietary habits. Especially intake of certain essential nutrients like vitamins has been shown to be beneficial in experimental studies and some clinical trials. Vitamin K (VK) is an essential nutrient involved in the blood clotting cascade, and there are considerable experimental data demonstrating its potential anticancer activity in several cancer types including prostate cancer. Previous in vitro and in vivo studies have focused mainly on anti-oxidative effects as the underlying anticancer mechanism of VK. However, recent studies reveal that VK inhibits the growth of cancer cells through other mechanisms, including apoptosis, cell cycle arrest, autophagy, and modulation of various transcription factors such as Myc and Fos. In the present review, we focus on the anticancer effect of dietary VK and its analogs on prostate cancer, with an emphasis on the signaling pathways that are activated following exposure to these compounds. This review also highlights the potential of VK and its derivatives as an adjuvant treatment in combination with other vitamins or with chemotherapeutic drugs. Based on our recent results and a review of the existing literature, we present evidence that VK and its derivatives can potentially be explored as cancer therapy, especially for prostate cancer. PMID:28915711

Information Seeking and Satisfaction with Information Sources Among Spouses of Men with Newly Diagnosed Local-Stage Prostate Cancer.

PubMed

Bansal, Aasthaa; Koepl, Lisel M; Fedorenko, Catherine R; Li, Chunyu; Smith, Judith Lee; Hall, Ingrid J; Penson, David F; Ramsey, Scott D

2018-04-01

Information sources about prostate cancer treatment and outcomes are typically designed for patients. Little is known about the availability and utility of information for partners. The objectives of our study were to evaluate information sources used by partners to understand prostate cancer management options, their perceived usefulness, and the relationship between sources used and satisfaction with treatment experience. A longitudinal survey of female partners of men newly diagnosed with local-stage prostate cancer was conducted in three different geographic regions. Partners and associated patients were surveyed at baseline (after patient diagnosis but prior to receiving therapy) and at 12 months following diagnosis. Information sources included provider, literature, friends or family members, Internet websites, books, traditional media, and support groups. Utility of an information source was defined as whether the partner would recommend it to caregivers of other patients with local-stage prostate cancer. Our study cohort included 179 partner-patient pairs. At diagnosis, partners consulted an average of 4.6 information sources. Non-Hispanic white partners were more likely than others to use friends and family as an information source (OR = 2.44, 95% CI (1.04, 5.56)). More educated partners were less likely to use support groups (OR = 0.31, 95% CI (0.14, 0.71)). At 12-month follow-up, partners were less likely to recommend books (OR = 0.23, 95% CI (0.11, 0.49)) compared to baseline. Partners consulted a large number of information sources in researching treatment options for local-stage prostate cancer and the types of sources accessed varied by race/ethnicity and educational attainment. Additional resources to promote selection of high-quality non-provider information sources are warranted to enable partners to better aid patients in their treatment decision-making process.

Evaluation of primary androgen deprivation therapy in prostate cancer patients using the J-CAPRA risk score

PubMed Central

Akaza, Hideyuki; Hinotsu, Shiro; Usami, Michiyuki; Ogawa, Osamu; Kitamura, Tadaichi; Suzuki, Kazuhiro; Tsukamoto, Taiji; Naito, Seiji; Namiki, Mikio; Hirao, Yoshihiko; Murai, Masaru

2013-01-01

Purpose: To determine the influence of maximal androgen blockade (MAB) and non-MAB hormonal therapy with an luteinizing hormone releasing hormone (LHRH) analog on overall survival of prostate cancer patients in the Japan Study Group of Prostate Cancer (J-CaP) registry according to risk, as assessed using the novel J-CAPRA risk instrument. To undertake a multivariate analysis combining J-CAPRA risk score, type of hormonal therapy and comorbidities, in order to assess their impact on overall survival. Methods: The J-CaP database includes men in Japan diagnosed with any stage of prostate cancer between 2001 and 2003 and treated with primary androgen deprivation therapy (PADT), as monotherapy or in combination. A total of 26,272 men were enrolled and of these 19,265 were treated with PADT. This analysis was undertaken using the latest data set (30 April, 2010) including a total of 15,727 patients who received PADT and had follow-up data for periods ranging from 0 to 9.2 years. Results: MAB for prostate cancer patients with intermediate- or high-risk disease has a significant benefit in terms of overall survival compared with LHRH analog monotherapy or surgical castration alone. Better results may be achieved in older (≥75 years) patients. Patient comorbidities are an important factor in determining overall survival, notably in older patients, and should be considered when selecting therapy. Conclusions: Based on large-scale registry data, this report is the first to analyze the outcomes of MAB therapy in patients with prostate cancer at a wide range of disease stages. MAB therapy may provide significant survival benefits in intermediate- and high-risk patients. PMID:24223407

Information Seeking and Satisfaction with Information Sources Among Spouses of Men with Newly Diagnosed Local-Stage Prostate Cancer

PubMed Central

Bansal, Aasthaa; Koepl, Lisel M.; Fedorenko, Catherine R.; Li, Chunyu; Smith, Judith Lee; Hall, Ingrid J.; Penson, David F.; Ramsey, Scott D.

2017-01-01

Information sources about prostate cancer treatment and outcomes are typically designed for patients. Little is known about the availability and utility of information for partners. The objectives of our study were to evaluate information sources used by partners to understand prostate cancer management options, their perceived usefulness, and the relationship between sources used and satisfaction with treatment experience. A longitudinal survey of female partners of men newly diagnosed with local-stage prostate cancer was conducted in three different geographic regions. Partners and associated patients were surveyed at baseline (after patient diagnosis but prior to receiving therapy) and at 12 months following diagnosis. Information sources included provider, literature, friends or family members, Internet websites, books, traditional media, and support groups. Utility of an information source was defined as whether the partner would recommend it to caregivers of other patients with local-stage prostate cancer. Our study cohort included 179 partner-patient pairs. At diagnosis, partners consulted an average of 4.6 information sources. Non-Hispanic white partners were more likely than others to use friends and family as an information source (OR = 2.44, 95% CI (1.04, 5.56)). More educated partners were less likely to use support groups (OR = 0.31, 95% CI (0.14, 0.71)). At 12-month follow-up, partners were less likely to recommend books (OR = 0.23, 95% CI (0.11, 0.49)) compared to baseline. Partners consulted a large number of information sources in researching treatment options for local-stage prostate cancer and the types of sources accessed varied by race/ethnicity and educational attainment. Additional resources to promote selection of high-quality non-provider information sources are warranted to enable partners to better aid patients in their treatment decision-making process. PMID:28238032

Expression and Function of the Progesterone Receptor in Human Prostate Stroma Provide Novel Insights to Cell Proliferation Control

PubMed Central

Yu, Yue; Liu, Liangliang; Xie, Ning; Xue, Hui; Fazli, Ladan; Buttyan, Ralph; Wang, Yuzhuo; Gleave, Martin

2013-01-01

Context: Like other tissues, the prostate is an admixture of many different cell types that can be segregated into components of the epithelium or stroma. Reciprocal interactions between these 2 types of cells are critical for maintaining prostate homeostasis, whereas aberrant stromal cell proliferation can disrupt this balance and result in diseases such as benign prostatic hyperplasia. Although the androgen and estrogen receptors are relatively well studied for their functions in controlling stromal cell proliferation and differentiation, the role of the progesterone receptor (PR) remains unclear. Objective: The aim of the study was to investigate the expression and function of the PR in the prostate. Design and Setting: Human prostate biopsies, renal capsule xenografts, and prostate stromal cells were used. Immunohistochemistry, Western blotting, real-time quantitative PCR, cell proliferation, flow cytometry, and gene microarray analyses were performed. Results: Two PR isoforms, PRA and PRB, are expressed in prostate stromal fibroblasts and smooth muscle cells, but not in epithelial cells. Both PR isoforms suppress prostate stromal cell proliferation through inhibition of the expression of cyclinA, cyclinB, and cdc25c, thus delaying cell cycling through S and M phases. Gene microarray analyses further demonstrated that PRA and PRB regulated different transcriptomes. However, one of the major gene groups commonly regulated by both PR isoforms was the one associated with regulation of cell proliferation. Conclusion: PR plays an inhibitory role in prostate stromal cell proliferation. PMID:23666965

Prostate Cancer—Health Professional Version

Cancer.gov

Prostate cancers are often adenocarcinomas. Prostatic intraepithelial neoplasia is often present in association with prostatic adenocarcinoma. Find evidence-based information on prostate cancer including treatment, causes and prevention, screening, research, genetics, and statistics.

Cell type specific gene expression analysis of prostate needle biopsies resolves tumor tissue heterogeneity

PubMed Central

Krönig, Malte; Walter, Max; Drendel, Vanessa; Werner, Martin; Jilg, Cordula A.; Richter, Andreas S.; Backofen, Rolf; McGarry, David; Follo, Marie; Schultze-Seemann, Wolfgang; Schüle, Roland

2015-01-01

A lack of cell surface markers for the specific identification, isolation and subsequent analysis of living prostate tumor cells hampers progress in the field. Specific characterization of tumor cells and their microenvironment in a multi-parameter molecular assay could significantly improve prognostic accuracy for the heterogeneous prostate tumor tissue. Novel functionalized gold-nano particles allow fluorescence-based detection of absolute mRNA expression levels in living cells by fluorescent activated flow cytometry (FACS). We use of this technique to separate prostate tumor and benign cells in human prostate needle biopsies based on the expression levels of the tumor marker alpha-methylacyl-CoA racemase (AMACR). We combined RNA and protein detection of living cells by FACS to gate for epithelial cell adhesion molecule (EPCAM) positive tumor and benign cells, EPCAM/CD45 double negative mesenchymal cells and CD45 positive infiltrating lymphocytes. EPCAM positive epithelial cells were further sub-gated into AMACR high and low expressing cells. Two hundred cells from each population and several biopsies from the same patient were analyzed using a multiplexed gene expression profile to generate a cell type resolved profile of the specimen. This technique provides the basis for the clinical evaluation of cell type resolved gene expression profiles as pre-therapeutic prognostic markers for prostate cancer. PMID:25514598

DNA Repair in Prostate Cancer: Biology and Clinical Implications.

PubMed

Mateo, Joaquin; Boysen, Gunther; Barbieri, Christopher E; Bryant, Helen E; Castro, Elena; Nelson, Pete S; Olmos, David; Pritchard, Colin C; Rubin, Mark A; de Bono, Johann S

2017-03-01

For more precise, personalized care in prostate cancer (PC), a new classification based on molecular features relevant for prognostication and treatment stratification is needed. Genomic aberrations in the DNA damage repair pathway are common in PC, particularly in late-stage disease, and may be relevant for treatment stratification. To review current knowledge on the prevalence and clinical significance of aberrations in DNA repair genes in PC, particularly in metastatic disease. A literature search up to July 2016 was conducted, including clinical trials and preclinical basic research studies. Keywords included DNA repair, BRCA, ATM, CRPC, prostate cancer, PARP, platinum, predictive biomarkers, and hereditary cancer. We review how the DNA repair pathway is relevant to prostate carcinogenesis and progression. Data on how this may be relevant to hereditary cancer and genetic counseling are included, as well as data from clinical trials of PARP inhibitors and platinum therapeutics in PC. Relevant studies have identified genomic defects in DNA repair in PCs in 20-30% of advanced castration-resistant PC cases, a proportion of which are germline aberrations and heritable. Phase 1/2 clinical trial data, and other supporting clinical data, support the development of PARP inhibitors and DNA-damaging agents in this molecularly defined subgroup of PC following success in other cancer types. These studies may be an opportunity to improve patient care with personalized therapeutic strategies. Key literature on how genomic defects in the DNA damage repair pathway are relevant for prostate cancer biology and clinical management is reviewed. Potential implications for future changes in patient care are discussed. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Association of dipeptidyl peptidase 4 inhibitors with risk of metastases in patients with type 2 diabetes and breast, prostate or digestive system cancer.

PubMed

Rathmann, Wolfgang; Kostev, Karel

2017-04-01

Experimental and animal studies have supported the hypothesis that dipeptidyl peptidase-4 inhibitors (DPP-4i) may accelerate tumor metastasis. The aim was to analyze the relationships between DPP-4i therapy with risk of metastases in type 2 diabetes patients with breast, prostate and digestive organ cancers. Type 2 diabetes patients with first diagnoses of breast, prostate or digestive organ cancer were selected in general and internal medicine practices (Disease Analyzer Germany: 01/2008-12/2014). Propensity score matching between DPP-4i users and non-users was carried out for age, sex, diabetes duration, and metformin use. Time-dependent Cox regression models were used to estimate hazard ratios (HR) for metastases further adjusting for HbA1c, body mass index, comorbidity and co-therapy with glucose-lowering drugs (3-4years follow-up). 668 patients with newly diagnosed breast cancer, 906 with prostate cancer and 908 with digestive organ cancer were analyzed. In Cox regression, use of DPP-4i was not associated with an increased risk of metastases in patients with breast (adjusted HR, 95%CI: 1.00, 0.49-2.02), prostate (0.98, 0.54-1.77) or digestive organ cancers (0.97, 0.57-1.66). This first observational study in patients with type 2 diabetes and breast, prostate or digestive organ cancer found no increased risk of metastases in DPP-4i users. Copyright © 2017 Elsevier Inc. All rights reserved.

Decreased fucosylated PSA as a urinary marker for high Gleason score prostate cancer.

PubMed

Fujita, Kazutoshi; Hayashi, Takuji; Matsuzaki, Kyosuke; Nakata, Wataru; Masuda, Mika; Kawashima, Atsunari; Ujike, Takeshi; Nagahara, Akira; Tsuchiya, Mutsumi; Kobayashi, Yuka; Nojima, Satoshi; Uemura, Motohide; Morii, Eiichi; Miyoshi, Eiji; Nonomura, Norio

2016-08-30

Fucosylation is an important oligosaccharide modification associated with cancer and inflammation. We investigated whether urinary fucosylated PSA (Fuc-PSA) levels could be used for the detection of high Gleason score prostate cancer. Urine samples were collected from men with abnormal digital rectal examination findings or elevated serum PSA levels, before prostate biopsy. Lectin-antibody ELISA was used to quantify the Lewis-type or core-type fucosylated PSA (PSA-AAL) and core-type fucosylated PSA (PSA-PhoSL) in the urine samples. Both types of urinary Fuc-PSA were significantly decreased in the men with prostate cancer compared with the men whose biopsies were negative for cancer (P = 0.026 and P < 0.001, respectively). Both were also significantly associated with the Gleason scores of the biopsy specimens (P = 0.001 and P < 0.001, respectively). Multivariate analysis showed that PSA density, urinary PSA-AAL, and urinary PSA-PhoSL were independent predictors of high Gleason score prostate cancer. The area under the receiver-operator characteristic curve (AUC) value for the prediction of cancers of Gleason score ≥ 7 was 0.69 for urinary PSA-AAL and 0.72 for urinary PSA-PhoSL. In contrast, the AUC value was 0.59 for serum PSA, 0.63 for PSA density, and 0.58 for urinary PSA. In conclusion, a decreased urinary Fuc-PSA level is a potential marker for the detection of high Gleason score prostate cancer.

Decreased fucosylated PSA as a urinary marker for high Gleason score prostate cancer

PubMed Central

Fujita, Kazutoshi; Hayashi, Takuji; Matsuzaki, Kyosuke; Nakata, Wataru; Masuda, Mika; Kawashima, Atsunari; Ujike, Takeshi; Nagahara, Akira; Tsuchiya, Mutsumi; Kobayashi, Yuka; Nojima, Satoshi; Uemura, Motohide; Morii, Eiichi; Miyoshi, Eiji; Nonomura, Norio

2016-01-01

Fucosylation is an important oligosaccharide modification associated with cancer and inflammation. We investigated whether urinary fucosylated PSA (Fuc-PSA) levels could be used for the detection of high Gleason score prostate cancer. Urine samples were collected from men with abnormal digital rectal examination findings or elevated serum PSA levels, before prostate biopsy. Lectin-antibody ELISA was used to quantify the Lewis-type or core-type fucosylated PSA (PSA-AAL) and core-type fucosylated PSA (PSA-PhoSL) in the urine samples. Both types of urinary Fuc-PSA were significantly decreased in the men with prostate cancer compared with the men whose biopsies were negative for cancer (P = 0.026 and P < 0.001, respectively). Both were also significantly associated with the Gleason scores of the biopsy specimens (P = 0.001 and P < 0.001, respectively). Multivariate analysis showed that PSA density, urinary PSA-AAL, and urinary PSA-PhoSL were independent predictors of high Gleason score prostate cancer. The area under the receiver-operator characteristic curve (AUC) value for the prediction of cancers of Gleason score ≥ 7 was 0.69 for urinary PSA-AAL and 0.72 for urinary PSA-PhoSL. In contrast, the AUC value was 0.59 for serum PSA, 0.63 for PSA density, and 0.58 for urinary PSA. In conclusion, a decreased urinary Fuc-PSA level is a potential marker for the detection of high Gleason score prostate cancer. PMID:27494861

75 FR 65340 - Secretarial Review and Publication of the Annual Report to Congress Submitted by the Contracted...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-22

... Lung cancer Major depression Osteoporosis Prostate cancer Rheumatoid arthritis and osteoarthritis... obstructive pulmonary disease, arthritis, diabetes, depression, and several types of cancers. There is also a... cancers; bone/joint diseases, including hip fracture, osteoporosis, and arthritis; and infection...

Clinicopathological Overview of Granulomatous Prostatitis: An Appraisal

PubMed Central

Dravid, Nandkumar; Nikumbh, Dhiraj; Patil, Ashish; Nagappa, Karibasappa Gundabaktha

2016-01-01

Introduction Granulomatous prostatitis is a rare inflammatory condition of the prostate. Granulomatous prostatitis is important because, it mimics prostatic carcinoma clinically and hence the diagnosis can be made only by histopathological examination. Aim To study the histomorphological features and to know the prevalence of granulomatous prostatitis. Materials and Methods Histopathological records of 1,203 prostatic specimens received in the Department of the Pathology over a period of five years (June 2009 – June 2014). Seventeen cases of histopathologically, diagnosed granulomatous prostatitis were retrieved and reterospective data was collected from the patient’s records. Results Out of 17 cases of granulomatous prostatitis, we encountered 9 cases of non-specific granulomatous prostatitis, 5 cases of xanthogranulomatous prostatitis and 3 cases of specific tubercular prostatitis. The common age ranged from 51-75 years (mean 63 years) with mean PSA level of 15.8ng/ml. Six patients showed focal hypoechoic areas on TRUS and 11 cases revealed hard and fixed nodule on DRE. Conclusion Non-specific granulomatous prostatitis is the most common type of granulomatous prostatitis. There is no specific pattern of clinical, biochemical and ultrasound findings that allows the diagnosis of granulomatous prostatitis or differentiates it from prostatic carcinoma. Hence, histomorphological diagnosis is the gold standard in differentiating various prostatic lesions. PMID:27014642

Noninvasive prostate cancer screening based on serum surface-enhanced Raman spectroscopy and support vector machine

NASA Astrophysics Data System (ADS)

Li, Shaoxin; Zhang, Yanjiao; Xu, Junfa; Li, Linfang; Zeng, Qiuyao; Lin, Lin; Guo, Zhouyi; Liu, Zhiming; Xiong, Honglian; Liu, Songhao

2014-09-01

This study aims to present a noninvasive prostate cancer screening methods using serum surface-enhanced Raman scattering (SERS) and support vector machine (SVM) techniques through peripheral blood sample. SERS measurements are performed using serum samples from 93 prostate cancer patients and 68 healthy volunteers by silver nanoparticles. Three types of kernel functions including linear, polynomial, and Gaussian radial basis function (RBF) are employed to build SVM diagnostic models for classifying measured SERS spectra. For comparably evaluating the performance of SVM classification models, the standard multivariate statistic analysis method of principal component analysis (PCA) is also applied to classify the same datasets. The study results show that for the RBF kernel SVM diagnostic model, the diagnostic accuracy of 98.1% is acquired, which is superior to the results of 91.3% obtained from PCA methods. The receiver operating characteristic curve of diagnostic models further confirm above research results. This study demonstrates that label-free serum SERS analysis technique combined with SVM diagnostic algorithm has great potential for noninvasive prostate cancer screening.

Transrectal Near-Infrared Optical Tomography for Prostate Imaging

DTIC Science & Technology

2010-03-01

valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE (DD-MM-YYYY) 31-03-2010 2. REPORT TYPE Annual 3...technology of trans-rectal near-infrared (NIR) optical tomography for accurate, selective prostate biopsy. Prostate cancer is the most common non ...mice and recovered/homogenized for injection into the non -immune suppressed dog’s prostate gland. Under general anesthesia, ~2 cc of TVT cells

Androgen Receptor Gene Polymorphisms and Alterations in Prostate Cancer: Of Humanized Mice and Men

PubMed Central

Robins, Diane M.

2011-01-01

Germline polymorphisms and somatic mutations of the androgen receptor (AR) have been intensely investigated in prostate cancer but even with genomic approaches their impact remains controversial. To assess the functional significance of AR genetic variation, we converted the mouse gene to the human sequence by germline recombination and engineered alleles to query the role of a polymorphic glutamine (Q) tract implicated in cancer risk. In a prostate cancer model, AR Q tract length influences progression and castration response. Mutation profiling in mice provides direct evidence that somatic AR variants are selected by therapy, a finding validated in human metastases from distinct treatment groups. Mutant ARs exploit multiple mechanisms to resist hormone ablation, including alterations in ligand specificity, target gene selectivity, chaperone interaction and nuclear localization. Regardless of their frequency, these variants permute normal function to reveal novel means to target wild type AR and its key interacting partners. PMID:21689727

Hyperglycemic condition during puberty increases collagen fibers deposition in the prostatic stroma and reduces MMP-2 activity.

PubMed

Santos, Sérgio Alexandre Alcantara Dos; Porto Amorim, Elaine Manoela; Ribeiro, Larissa Mayume; Rinaldi, Jaqueline Carvalho; Delella, Flávia Karina; Justulin, Luis Antonio; Felisbino, Sérgio Luis

2017-12-02

Puberty is an important period for the growth and maturation of the male reproductive system, and is also a critical window for endocrine or environmental interference. The physiological levels of circulating insulin and hyperglycemic control are important factors for a normal prostate growth. Hyperglycemia during puberty is reported to retard the growth of the prostate gland, with remarkable effects on the epithelial compartment. Here, we investigated the impact of hyperglycemia along with a simultaneous or late insulin replacement on the ventral prostate growth in rats during puberty, paying special attention to the deposition of collagen fibers and activities of gelatinase, matrix metalloproteinase-2 (MMP-2), and -9 (MMP-9). Hyperglycemia was induced by streptozotocin (STZ) administration in 40-day-old male Wistar rats. A subset of hyperglycemic rats underwent an early insulin replacement (three days after the STZ administration), and another subset underwent a late insulin replacement (twenty days after the STZ administration). Animals were euthanized at 60 and/or 80 days of age. The ventral prostatic lobe was processed for picrosirius red staining, type I and III collagen immunohistochemistry, and gelatin zymography. Hyperglycemic animals showed an increased area of collagen fibers in the prostate, which was composed both types of collagens. MMP-2 activity was significantly reduced in the hyperglycemic animals, while MMP-9 activity was very low and showed no alteration. The simultaneous and late insulin administration restored collagen content and MMP-2 activity. In conclusion, puberty is a critical window for prostate maturation and type-1 diabetes-induced hyperglycemia affects the ratio of the prostatic parenchymal and stromal growth, leading to fibrotic tissues by also MMP-2 down regulation. Copyright © 2017 Elsevier Inc. All rights reserved.

[Clinical efficacy of Shuganyiyang capsule combined with Western medicine for the treatment of type III prostatitis complicated by erectile dysfunction].

PubMed

Feng, Yi-Geng; Chen, Lei; Zhou, Zhi-Heng

2013-11-01

To investigate the clinical efficacy of Shuganyiyang Capsule combined with conventional Western medicine (tamsulosin hydrochloride sustained release tablets + prostat tablets) for the treatment of type III prostatitis complicated by erectile dysfunction (ED). Eighty patients with type III prostatitis complicated by ED were equally randomized to an experimental and a control group, the former treated with Shuganyiyang Capsule combined with tamsulosin hydrochloride sustained release tablets and prostat tablets, while the latter with tamsulosin hydrochloride and prostat only, both for 8 weeks. Then the prostatitis symptoms, erectile function and psychological conditions of the patients were evaluated using NIH-CPSI, IIEF-5, and hospital anxiety and depression scale (HADA and HADD) respectively. The rates of recovery, excellence, effectiveness and ineffectiveness were calculated. The scores on NIH-CPSI, IIEF-5, HADA and HADD obtained at 4 and 8 weeks after treatment showed statistically significant differences between the two time points as well as from the baseline (P < 0.01). At 8 weeks, the scores on NIH-CPSI, IIEF-5, HADA and HADD were 6.83 +/- 4.96, 21.03 +/- 2.54, 6.05 +/- 1.62, and 5.35 +/- 3.30 in the experimental group, as compared with 7.55 +/- 4.89, 17.68 +/- 4.15, 6.88 +/- 2.45, and 7.85 +/- 3.77 in the control (P < 0.05). The rate of effectiveness was significantly higher in the experimental than in the control group (90% [36/40] vs 70% [28/40], P < 0.05). Shuganyiyang Capsule combined with conventional Western medicine, such as alpha blockers and galenica, produces definite effect on chronic prostatitis complicated by ED, improves the psychological conditions of the patient, and enhances the therapeutic efficiency of chronic prostatits.

Spondyloarthritis, Acute Anterior Uveitis, and Fungi: Updating the Catterall–King Hypothesis

PubMed Central

Laurence, Martin; Asquith, Mark; Rosenbaum, James T.

2018-01-01

Spondyloarthritis is a common type of arthritis which affects mostly adults. It consists of idiopathic chronic inflammation of the spine, joints, eyes, skin, gut, and prostate. Inflammation is often asymptomatic, especially in the gut and prostate. The HLA-B*27 allele group, which presents intracellular peptides to CD8+ T cells, is by far the strongest risk factor for spondyloarthritis. The precise mechanisms and antigens remain unknown. In 1959, Catterall and King advanced a novel hypothesis explaining the etiology of spondyloarthritis: an as-yet-unrecognized sexually acquired microbe would be causing all spondyloarthritis types, including acute anterior uveitis. Recent studies suggest an unrecognized sexually acquired fungal infection may be involved in prostate cancer and perhaps multiple sclerosis. This warrants reanalyzing the Catterall–King hypothesis based on the current literature. In the last decade, many links between spondyloarthritis and fungal infections have been found. Antibodies against the fungal cell wall component mannan are elevated in spondyloarthritis. Functional polymorphisms in genes regulating the innate immune response against fungi have been associated with spondyloarthritis (CARD9 and IL23R). Psoriasis and inflammatory bowel disease, two common comorbidities of spondyloarthritis, are both strongly associated with fungi. Evidence reviewed here lends credence to the Catterall–King hypothesis and implicates a common fungal etiology in prostate cancer, benign prostatic hyperplasia, multiple sclerosis, psoriasis, inflammatory bowel disease, and spondyloarthritis. However, the evidence available at this time is insufficient to definitely confirm this hypothesis. Future studies investigating the microbiome in relation to these conditions should screen specimens for fungi in addition to bacteria. Future clinical studies of spondyloarthritis should consider antifungals which are effective in psoriasis and multiple sclerosis, such as dimethyl fumarate and nystatin. PMID:29675414

Insulin receptor isoforms A and B as well as insulin receptor substrates-1 and -2 are differentially expressed in prostate cancer.

PubMed

Heni, Martin; Hennenlotter, Jörg; Scharpf, Marcus; Lutz, Stefan Z; Schwentner, Christian; Todenhöfer, Tilman; Schilling, David; Kühs, Ursula; Gerber, Valentina; Machicao, Fausto; Staiger, Harald; Häring, Hans-Ulrich; Stenzl, Arnulf

2012-01-01

In different cancers types, insulin receptor isoform composition or insulin receptor substrate (IRS) isoforms are different to healthy tissue. This may be a molecular link to increased cancer risk in diabetes and obesity. Since this is yet unclear for prostate cancer, we investigated IR isoform composition and IRS balance in prostate cancer compared to benign and tumor adjacent benign prostate tissue and brought this into relation to cell proliferation. We studied 23 benign prostate samples from radical cystectomy or benign prostatic hyperplasia surgery, 30 samples from benign tissue directly adjacent to prostate cancer foci and 35 cancer samples from different patients. RNA expression levels for insulin receptor isoforms A and B, IRS-1, IRS-2, and IGF-1 receptor were assessed by quantitative real-time RT-PCR. In addition, RNA- and protein expression of the cell cycle regulator p27(Kip1) was quantified by real-time RT-PCR and immunohistochemistry. Insulin receptor isoform A to B ratio was significantly higher in cancer as well as in tumor adjacent benign prostate tissue compared to purely benign prostates (p<0.05). IRS-1 to IRS-2 ratios were lower in malignant than in benign prostatic tissue (p<0.05). These altered ratios both in cancer and adjacent tissue were significantly associated with reduced p27(Kip1) content (p<0.02). Interestingly, IGF-1 receptor levels were significantly lower in patients with type 2 diabetes (p = 0.0019). We found significant differences in the insulin signaling cascade between benign prostate tissue and prostate cancer. Histological benign tissue adjacent to cancer showed expression patterns similar to the malignancies. Our findings suggest a role of the insulin signaling pathway in prostate cancer and surrounding tissue and can hence be relevant for both novel diagnostic and therapeutic approaches in this malignancy.

Metformin for Reducing Racial/Ethnic Difference in Prostate Cancer Incidence for Men with Type II Diabetes.

PubMed

Wang, Chen-Pin; Lehman, Donna M; Lam, Yui-Wing F; Kuhn, John G; Mahalingam, Devalingam; Weitman, Steven; Lorenzo, Carlos; Downs, John R; Stuart, Elizabeth A; Hernandez, Javier; Thompson, Ian M; Ramirez, Amelie G

2016-10-01

Racial/ethnic disparity in prostate cancer is under studied in men with diabetes who are at a higher risk of aggressive prostate cancer. This study assessed the race/ethnic disparity in prostate cancer incidence for men with type II diabetes (T2D) and whether the impact of metformin on prostate cancer incidence varied by race/ethnicity. We conducted a retrospective study in 76,733 male veterans with T2D during 2003 to 2012. Cox proportional hazards model adjusting for covariates and propensity scores of metformin use and race/ethnic group membership was utilized to compute the HR of prostate cancer incidence associated with race/ethnicity and compare HR associated with metformin use between race/ethnic groups. Mean follow-up was 6.4 ± 2.8 years; 7% were Hispanics; 17% were African Americans (AA); mean age was 67.8 ± 9.8 years; 5.2% developed prostate cancer; and 38.9% used metformin. Among these diabetic men without metformin use, prostate cancer incidence was higher in Hispanics and AA than in non-Hispanic White (NHW). Use of metformin alone or metformin + statins was associated with a greater prostate cancer incidence reduction in Hispanics compared with NHW, but not between AA and NHW. Use of metformin + finasteride was associated with a greater prostate cancer incidence reduction in Hispanics and AA compared with NHW. Our results suggested that metformin treatment could be a potential strategy to reduce prostate cancer incidence in the minority populations who are at high risk for fatal prostate cancer. It will be important to further examine the pleiotropic effects of metformin in multi-race/ethnic prospective studies to better inform clinical management and potentially reduce racial/ethnic disparity in prostate cancer incidence among diabetic men. Cancer Prev Res; 9(10); 779-87. ©2016 AACR. ©2016 American Association for Cancer Research.

Race and survival following brachytherapy-based treatment for men with localized or locally advanced adenocarcinoma of the prostate.

PubMed

Winkfield, Karen M; Chen, Ming-Hui; Dosoretz, Daniel E; Salenius, Sharon A; Katin, Michael; Ross, Rudi; D'Amico, Anthony V

2011-11-15

We investigated whether race was associated with risk of death following brachytherapy-based treatment for localized prostate cancer, adjusting for age, cardiovascular comorbidity, treatment, and established prostate cancer prognostic factors. The study cohort was composed of 5,360 men with clinical stage T1-3N0M0 prostate cancer who underwent brachytherapy-based treatment at 20 centers within the 21st Century Oncology consortium. Cox regression multivariable analysis was used to evaluate the risk of death in African-American and Hispanic men compared to that in Caucasian men, adjusting for age, pretreatment prostate-specific antigen (PSA) level, Gleason score, clinical T stage, year and type of treatment, median income, and cardiovascular comorbidities. After a median follow-up of 3 years, there were 673 deaths. African-American and Hispanic races were significantly associated with an increased risk of all-cause mortality (ACM) (adjusted hazard ratio, 1.77 and 1.79; 95% confidence intervals, 1.3-2.5 and 1.2-2.7; p < 0.001 and p = 0.005, respectively). Other factors significantly associated with an increased risk of death included age (p < 0.001), Gleason score of 8 to 10 (p = 0.04), year of brachytherapy (p < 0.001), and history of myocardial infarction treated with stent or coronary artery bypass graft (p < 0.001). After adjustment for prostate cancer prognostic factors, age, income level, and revascularized cardiovascular comorbidities, African-American and Hispanic races were associated with higher ACM in men with prostate cancer. Additional causative factors need to be identified. Copyright © 2011 Elsevier Inc. All rights reserved.

Evolution of primary care referrals to urology. Impact of a protocol on prostate disease and continuing education.

PubMed

Sopeña-Sutil, R; Tejido-Sánchez, A; Galván-Ortiz de Urbina, M; Guerrero-Ramos, F; García-Álvarez, G; Passas-Martínez, J B

2015-06-01

To analyze the evolution of primary care referrals to the Urology Department after the implementation of a joint protocol on prostate disease and a continuing education program in our healthcare area. In January 2011, we launched an action protocol on prostate disease, which was complemented by training sessions and an e-mail-based consultation system. We analyzed primary care referrals to the Urology Department between 2011 and 2013 and determined the reasons for the consultations and the compliance with the established criteria on prostate disease. We obtained data from the "Request for Appointment in Specialized Care" program of the Community of Madrid. We calculated the sample size with a 95% confidence level and a 50% heterogeneity. A total of 19,048 referrals were conducted. The most common reason for the referrals was lower urinary tract symptoms associated with benign prostate hyperplasia, with a 27% reduction and a compliance that went from 46% at 67%. Although prostate-specific antigen consultations increased by 40%, they improved their appropriateness (from 55% to 72%). This was the main type of consultation for suspicion of malignancy (30%). Also worth mentioning were female incontinence, which doubled in number, and a 41% reduction in erectile dysfunction, which could be due to the primary care training. The collaboration between the Department of Urology and primary care succeeded in improving the appropriateness of prostate disease referrals and modified the tendency to refer the rest of the diseases included in the project. Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Evaluation of the protective effect of pentoxifylline on carrageenan-induced chronic non-bacterial prostatitis in rats.

PubMed

Hajighorbani, Mahboobeh; Ahmadi-Hamedani, Mahmood; Shahab, Elaheh; Hayati, Farzad; Kafshdoozan, Khatereh; Keramati, Keivan; Amini, Amin Hossein

2017-06-01

Chronic non-bacterial prostatitis (CNP) is the most common type of prostatitis and oxidative stress (OS) was shown to be highly elevated in prostatitis patients. This study aimed to investigate the protective effect of pentoxifylline (PTX) on CNP induced by carrageenan in rats. Male adult Wistar rats (n = 30) were divided into control, CNP and three treatment groups (n = 6) including CNP + cernilton and CNP + PTX groups. CNP was induced by single intraprostatic injection of 1% carrageenan (100 µl). Rats in treatment groups received orally cernilton 100 mg/kg and PTX at 50 and 100 mg/kg 1 week after CNP induction for 21 days. Prostatic index (PI), prostatic specific antigen (PSA), tumor-necrosis factor alpha (TNF-α), serum lipid peroxidation (MDA), blood urea nitrogen, creatinine and histopathological changes were compared between groups. There were significant increase of PI, serum levels of PSA, TNF-α and MDA in CNP group at 29 day. In treatment groups, significant reduction in PI, serum levels of PSA, TNF-α, MDA and creatinine was observed especially in rats treated with dose of 50 mg/kg of PTX. In CNP group, histopathological changes of the prostate such as leucocyte infiltration, large involutions and projection into the lumen and reducing the volume of the lumen were observed as well. Whereas PTX, especially at dose of 50 mg/kg, could improve the above-mentioned changes remarkably in CNP treated rats. For the first time, our findings indicated that PTX improved CNP induced by carrageenan in rats.

Configuration and validation of a novel prostate disease nomogram predicting prostate biopsy outcome: A prospective study correlating clinical indicators among Filipino adult males with elevated PSA level.

PubMed

Chua, Michael E; Tanseco, Patrick P; Mendoza, Jonathan S; Castillo, Josefino C; Morales, Marcelino L; Luna, Saturnino L

2015-04-01

To configure and validate a novel prostate disease nomogram providing prostate biopsy outcome probabilities from a prospective study correlating clinical indicators and diagnostic parameters among Filipino adult male with elevated serum total prostate specific antigen (PSA) level. All men with an elevated serum total PSA underwent initial prostate biopsy at our institution from January 2011 to August 2014 were included. Clinical indicators, diagnostic parameters, which include PSA level and PSA-derivatives, were collected as predictive factors for biopsy outcome. Multiple logistic-regression analysis involving a backward elimination selection procedure was used to select independent predictors. A nomogram was developed to calculate the probability of the biopsy outcomes. External validation of the nomogram was performed using separate data set from another center for determination of sensitivity and specificity. A receiver-operating characteristic (ROC) curve was used to assess the accuracy in predicting differential biopsy outcome. Total of 552 patients was included. One hundred and ninety-one (34.6%) patients had benign prostatic hyperplasia, and 165 (29.9%) had chronic prostatitis. The remaining 196 (35.5%) patients had prostate adenocarcinoma. The significant independent variables used to predict biopsy outcome were age, family history of prostate cancer, prior antibiotic intake, PSA level, PSA-density, PSA-velocity, echogenic findings on ultrasound, and DRE status. The areas under the receiver-operating characteristic curve for prostate cancer using PSA alone and the nomogram were 0.688 and 0.804, respectively. The nomogram configured based on routinely available clinical parameters, provides high predictive accuracy with good performance characteristics in predicting the prostate biopsy outcome such as presence of prostate cancer, high Gleason prostate cancer, benign prostatic hyperplasia, and chronic prostatitis.

Differential expression of extracellular matrix molecules and the alpha 6-integrins in the normal and neoplastic prostate.

PubMed Central

Knox, J. D.; Cress, A. E.; Clark, V.; Manriquez, L.; Affinito, K. S.; Dalkin, B. L.; Nagle, R. B.

1994-01-01

The epithelial basal lamina composition and integrin expression profile of normal and neoplastic human prostate was characterized using immunohistochemical analysis of frozen samples. The major components of the basal lamina surrounding normal acini were laminin, type IV collagen, entactin, and type VII collagen with variable amounts of tenascin. The basal lamina of neoplastic acini had a similar composition, except for the loss of type VII collagen, which was observed in all grades of carcinoma. The basal cells of the normal prostate express the alpha 6-, beta 1-, and beta 4-integrin subunits, suggesting that both the alpha 6 beta 1- and alpha 6 beta 4-integrin complexes are formed. In prostate carcinoma there is a complete loss of beta 4 expression and the alpha 6- and beta 1-integrin subunits, which are restricted to the basal and basal lateral surfaces of basal cells, are distributed diffusely throughout the cytoplasmic membrane. The differential expression of type VII collagen and beta 4 are discussed in relationship to their possible role in tumor progression. Images Figure 1 Figure 2 Figure 3 PMID:8030747

Prostate Cancer Screening (PDQ®)—Patient Version

Cancer.gov

Prostate cancer screening may help detect prostate cancer, but remains controversial as it has not been shown to reduce deaths from prostate cancer. Learn more about prostate cancer screening, including the potential benefits and harms, in this expert-reviewed information summary.

Prostate Cancer Screening (PDQ®)—Health Professional Version

Cancer.gov

Prostate cancer screening with the prostate-specific antigen (PSA) test or digital rectal exams has not been shown to reduce prostate cancer deaths. Get detailed information about prostate cancer screening, including potential benefits and harms, in this summary for clinicians.

Selective Activation of a Perforin-Granzyme B Fusion Protein Toxin by PSA as Therapy for Metastatic Prostate Cancer

DTIC Science & Technology

2016-10-01

Prostate Cancer PRINCIPAL INVESTIGATOR: Samuel Denmeade RECIPIENT: Johns Hopkins University Baltimore, MD 21218 REPORT DATE: October 2016 TYPE...PSA as Therapy for Metastatic Prostate Cancer 5b. GRANT NUMBER W81XWH-15-1-0382 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Samuel R Denmeade...cytotoxic agent that can selectively kill both proliferating and non-proliferating prostate cancer cells within a metastatic site without significant host

Tadalafil for lower urinary tract symptoms secondary to benign prostatic hyperplasia: a review of clinical data in Asian men and an update on the mechanism of action

PubMed Central

Igawa, Yasuhiko; Takeda, Masayuki; Yamaguchi, Takafumi; Murakami, Masahiro; Viktrup, Lars

2015-01-01

Tadalafil, a phosphodiesterase type 5 (PDE5) inhibitor, is approved worldwide for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH-LUTS). The purpose of this narrative review is to summarize the clinical data on tadalafil 5 mg once-daily, primarily focusing on Asian men with BPH-LUTS, and to update the current understanding of the mechanism of action underlying PDE5 inhibition. Findings from studies have demonstrated that PDE5 is highly expressed in the lower urinary tract and supporting vasculature, and that PDE5 inhibition potentially decreases smooth muscle cell proliferation in the prostate, relaxes smooth muscle in the prostate, bladder neck and supporting vasculature, increases blood perfusion to the lower urinary tract, and modulates bladder afferent nerve activity. A total of 11 larger, 12-week, double-blind, randomized, placebo-controlled studies of tadalafil, including four Asian studies, have been conducted globally, enrolling >3000 men with BPH-LUTS. In addition, two long-term (42- and 52-week) studies enrolled 394 Japanese and 428 North American men, respectively, with BPH-LUTS. Overall, tadalafil 5 mg once-daily resulted in significant improvements in the change from baseline to endpoint in total International Prostate Symptom Scores (IPSS), IPSS storage and voiding subscores, and IPSS quality of life index compared with placebo. Tadalafil was well tolerated and had a favorable safety profile. These findings support tadalafil 5 mg once-daily for treating men, including Asian men, with BPH-LUTS. PMID:26425140

Comprehensive overview of prostatitis.

PubMed

Khan, Farhan Ullah; Ihsan, Awais Ullah; Khan, Hidayat Ullah; Jana, Ruby; Wazir, Junaid; Khongorzul, Puregmaa; Waqar, Muhammad; Zhou, Xiaohui

2017-10-01

Prostatitis is a common urinary tract syndrome that many doctors find problematic to treat effectively. It is the third most commonly found urinary tract disease in men after prostate cancer and Benign Prostate Hyperplasia (BPH). Prostatitis may account for 25% of all office visits made to the urological clinics complaining about the genital and urinary systems all over the world. In the present study, we classified prostatitis and comprehensively elaborated the etiology, pathogenesis, diagnosis, and treatment of acute bacterial prostatitis (category I), chronic bacterial prostatitis (category II), chronic pelvic pain syndrome (CPPS) (category III), and asymptomatic prostatitis (category IV). In addition, we also tried to get some insights about other types of prostatitis-like fungal, viral and gonococcal prostatitis. The aim of this review is to present the detail current perspective of prostatitis in a single review. To the best of our knowledge currently, there is not a single comprehensive review, which can completely elaborate this important topic in an effective way. Furthermore, this review will provide a solid platform to conduct future studies on different aspects such as risk factors, mechanism of pathogenesis, proper diagnosis, and rational treatment plans for fungal, viral, and gonococcal prostatitis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Magnetic resonance imaging in active surveillance—a modern approach

PubMed Central

Moore, Caroline M.

2018-01-01

In recent years, active surveillance has been increasingly adopted as a conservative management approach to low and sometimes intermediate risk prostate cancer, to avoid or delay treatment until there is evidence of higher risk disease. A number of studies have investigated the role of multiparametric magnetic resonance imaging (mpMRI) in this setting. MpMRI refers to the use of multiple MRI sequences (T2-weighted anatomical and functional imaging which can include diffusion-weighted imaging, dynamic contrast enhanced imaging, spectroscopy). Each of the parameters investigates different aspects of the prostate gland (anatomy, cellularity, vascularity, etc.). In addition to a qualitative assessment, the radiologist can also extrapolate quantitative imaging biomarkers from these sequences, for example the apparent diffusion coefficient from diffusion-weighted imaging. There are many different types of articles (e.g., reviews, commentaries, consensus meetings, etc.) that address the use of mpMRI in men on active surveillance for prostate cancer. In this paper, we compare original articles that investigate the role of the different mpMRI sequences in men on active surveillance for prostate cancer, in order to discuss the relative utility of the different sequences, and combinations of sequences. We searched MEDLINE/PubMed for manuscripts published from inception to 1st December 2017. The search terms used were (prostate cancer or prostate adenocarcinoma or prostatic carcinoma or prostate carcinoma or prostatic adenocarcinoma) and (MRI or NMR or magnetic resonance imaging or mpMRI or multiparametric MRI) and active surveillance. Overall, 425 publications were found. All abstracts were reviewed to identify papers with original data. Twenty-five papers were analysed and summarised. Some papers based their analysis only on one mpMRI sequence, while others assessed two or more. The evidence from this review suggests that qualitative assessments and quantitative data from different mpMRI sequences hold promise in the management of men on active surveillance for prostate cancer. Both qualitative and quantitative approaches should be considered when assessing mpMRI of the prostate. There is a need for robust studies assessing the relative utility of different combinations of sequences in a systematic manner to determine the most efficient use of mpMRI in men on active surveillance. PMID:29594026

Decreased expression of Toll-like receptor 4 and 5 during progression of prostate transformation in transgenic adenocarcinoma of mouse prostate mice.

PubMed

Han, Ju-Hee; Park, Jong-Hwan; Kim, Bo-Yeon; Chang, Seo-Na; Kim, Tae-Hyoun; Park, Jae-Hak; Kim, Dong-Jae

2015-01-01

Chronic inflammation has been considered an important risk factor for development of prostate cancer. Toll-like receptors (TLRs) recognize microbial moieties or endogenous molecules and play an important role in the triggering and promotion of inflammation. In this study, we examined whether expression of TLR4 and TLR5 was associated with progression of prostate transformation in the transgenic adenocarcinoma of mouse prostate (TRAMP) model. The expression of TLR4 and TLR5 was evaluated by immunohistochemisty in formalin-fixed paraffin-embedded prostate tissue from wild-type (WT) and TRAMP mice. Normal prostate tissue from WT mice showed strong expression of TLR4 and TLR5. However, TLR4 expression in the prostate tissue from TRAMP mice gradually decreased as pathologic grade became more aggressive. TLR5 expression in the prostate tissue from TRAMP mice also decreased in low-grade prostate intraepithelial neoplasia (PIN), high-grade PIN and poorly differentiated adenocarcinoma. Overall, our results suggest that decreased expression of TLR4 and TLR5 may contribute to prostate tumorigenesis.

Transcriptome instability as a molecular pan-cancer characteristic of carcinomas.

PubMed

Sveen, Anita; Johannessen, Bjarne; Teixeira, Manuel R; Lothe, Ragnhild A; Skotheim, Rolf I

2014-08-10

We have previously proposed transcriptome instability as a genome-wide, pre-mRNA splicing-related characteristic of colorectal cancer. Here, we explore the hypothesis of transcriptome instability being a general characteristic of cancer. Exon-level microarray expression data from ten cancer datasets were analyzed, including breast cancer, cervical cancer, colorectal cancer, gastric cancer, lung cancer, neuroblastoma, and prostate cancer (555 samples), as well as paired normal tissue samples from the colon, lung, prostate, and stomach (93 samples). Based on alternative splicing scores across the genomes, we calculated sample-wise relative amounts of aberrant exon skipping and inclusion. Strong and non-random (P < 0.001) correlations between these estimates and the expression levels of splicing factor genes (n = 280) were found in most cancer types analyzed (breast-, cervical-, colorectal-, lung- and prostate cancer). This suggests a biological explanation for the splicing variation. Surprisingly, these associations prevailed in pan-cancer analyses. This is in contrast to the tissue and cancer specific patterns observed in comparisons across healthy tissue samples from the colon, lung, prostate, and stomach, and between paired cancer-normal samples from the same four tissue types. Based on exon-level expression profiling and computational analyses of alternative splicing, we propose transcriptome instability as a molecular pan-cancer characteristic. The affected cancers show strong and non-random associations between low expression levels of splicing factor genes, and high amounts of aberrant exon skipping and inclusion, and vice versa, on a genome-wide scale.

Investigation of factors affecting hypothermic pelvic tissue cooling using bio-heat simulation based on MRI-segmented anatomic models.

PubMed

Lin, Yuting; Lin, Wei-Ching; Fwu, Peter T; Shih, Tzu-Ching; Yeh, Lee-Ren; Su, Min-Ying; Chen, Jeon-Hor

2015-10-01

This study applied a simulation method to map the temperature distribution based on magnetic resonance imaging (MRI) of individual patients, and investigated the influence of different pelvic tissue types as well as the choice of thermal property parameters on the efficiency of endorectal cooling balloon (ECB). MR images of four subjects with different prostate sizes and pelvic tissue compositions, including fatty tissue and venous plexus, were analyzed. The MR images acquired using endorectal coil provided a realistic geometry of deformed prostate that resembled the anatomy in the presence of ECB. A single slice with the largest two-dimensional (2D) cross-sectional area of the prostate gland was selected for analysis. The rectal wall, prostate gland, peri-rectal fatty tissue, peri-prostatic fatty tissue, peri-prostatic venous plexus, and urinary bladder were manually segmented. Pennes' bioheat thermal model was used to simulate the temperature distribution dynamics, by using an in-house finite element mesh based solver written in MATLAB. The results showed that prostate size and periprostatic venous plexus were two major factors affecting ECB cooling efficiency. For cases with negligible amount of venous plexus and small prostate, the average temperature in the prostate and neurovascular bundles could be cooled down to 25 °C within 30 min. For cases with abundant venous plexus and large prostate, the temperature could not reach 25 °C at the end of 3 h cooling. Large prostate made the cooling difficult to propagate through. The impact of fatty tissue on cooling effect was small. The filling of bladder with warm urine during the ECB cooling procedure did not affect the temperature in the prostate or NVB. In addition to the 2D simulation, in one case a 3D pelvic model was constructed for volumetric simulation. It was found that the 2D slice with the largest cross-sectional area of prostate had the most abundant venous plexus, and was the most difficult slice to cool, thus it may provide a conservative prediction of the cooling effect. This feasibility study demonstrated that the simulation tool could potentially be used for adjusting the setting of ECB for individual patients during hypothermic radical prostatectomy. Further studies using MR thermometry are required to validate the in silico results obtained using simulation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Investigation of factors affecting hypothermic pelvic tissue cooling using bio-heat simulation based on MRI-segmented anatomic models

PubMed Central

Lin, Yuting; Lin, Wei-Ching; Fwu, Peter T.; Shih, Tzu-Ching; Yeh, Lee-Ren; Su, Min-Ying; Chen, Jeon-Hor

2015-01-01

This study applied a simulation method to map the temperature distribution based on magnetic resonance imaging (MRI) of individual patients, and investigated the influence of different pelvic tissue types as well as the choice of thermal property parameters on the efficiency of endorectal cooling balloon (ECB). MR images of four subjects with different prostate sizes and pelvic tissue compositions, including fatty tissue and venous plexus, were analyzed. The MR images acquired using endorectal coil provided a realistic geometry of deformed prostate that resembled the anatomy in the presence of ECB. A single slice with the largest two-dimensional (2D) cross-sectional area of the prostate gland was selected for analysis. The rectal wall, prostate gland, peri-rectal fatty tissue, peri-prostatic fatty tissue, peri-prostatic venous plexus, and urinary bladder were manually segmented. Pennes’ bioheat thermal model was used to simulate the temperature distribution dynamics, by using an in-house finite element mesh based solver written in Matlab. The results showed that prostate size and periprostatic venous plexus were two major factors affecting ECB cooling efficiency. For cases with negligible amount of venous plexus and small prostate, the averaged temperature in the prostate and neurovascular bundles could be cooled down to 25°C within 30 minutes. For cases with abundant venous plexus and large prostate, the temperature could not reach 25°C at the end of 3 hours cooling. Large prostate made the cooling difficult to propagate through. The impact of fatty tissue on cooling effect was small. The filling of bladder with warm urine during the ECB cooling procedure did not affect the temperature in the prostate or NVB. In addition to the 2D simulation, in one case a 3D pelvic model was constructed for volumetric simulation. It was found that the 2D slice with the largest cross-sectional area of prostate had the most abundant venous plexus, and was the most difficult slice to cool, thus it may provide a conservative prediction of the cooling effect. This feasibility study demonstrated that the simulation tool could potentially be used for adjusting the setting of ECB for individual patients during hypothermic radical prostatectomy. Further studies using MR thermometry are required to validate the in silico results obtained using simulation. PMID:26198131

Prostate Ultrasound

MedlinePlus Videos and Cool Tools

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The Androgen-Regulated Calcium-Activated Nucleotidase 1 (CANT1) Is Commonly Overexpressed in Prostate Cancer and Is Tumor-Biologically Relevant in Vitro

PubMed Central

Gerhardt, Josefine; Steinbrech, Corinna; Büchi, Oralea; Behnke, Silvia; Bohnert, Annette; Fritzsche, Florian; Liewen, Heike; Stenner, Frank; Wild, Peter; Hermanns, Thomas; Müntener, Michael; Dietel, Manfred; Jung, Klaus; Stephan, Carsten; Kristiansen, Glen

2011-01-01

Previously, we identified the calcium-activated nucleotidase 1 (CANT1) transcript as up-regulated in prostate cancer. Now, we studied CANT1 protein expression in a large cohort of nearly 1000 prostatic tissue samples including normal tissue, prostatic intraepithelial neoplasia (PIN), primary carcinomas, metastases, and castrate-resistant carcinomas, and further investigated its functional relevance. CANT1 displayed predominantly a Golgi-type immunoreactivity with additional and variable cytoplasmic staining. In comparison to normal tissues, the staining intensity was significantly increased in PIN lesions and cancer. In cancer, high CANT1 levels were associated with a better prognosis, and castrate-resistant carcinomas commonly showed lower CANT1 levels than primary carcinomas. The functional role of CANT1 was investigated using RNA interference in two prostate cancer cell lines with abundant endogenous CANT1 protein. On CANT1 knockdown, a significantly diminished cell number and DNA synthesis rate, a cell cycle arrest in G1 phase, and a strong decrease of cell transmigration rate and wound healing capacity of CANT1 knockdown cells was found. However, on forced CANT1 overexpression, cell proliferation and migration remained unchanged. In summary, CANT1 is commonly overexpressed in the vast majority of primary prostate carcinomas and in the precursor lesion PIN and may represent a novel prognostic biomarker. Moreover, this is the first study to demonstrate a functional involvement of CANT1 in tumor biology. PMID:21435463

Does Radiotherapy for the Primary Tumor Benefit Prostate Cancer Patients with Distant Metastasis at Initial Diagnosis?

PubMed Central

Cho, Yeona; Chang, Jee Suk; Rha, Koon Ho; Hong, Sung Joon; Choi, Young Deuk; Ham, Won Sik; Kim, Jun Won; Cho, Jaeho

2016-01-01

Purpose/Objectives Treatment of the primary tumor reportedly improves survival in several types of metastatic cancer. We herein evaluated the efficacy and toxicity of radiotherapy for the primary tumor in prostate cancer with metastasis. Materials/Methods The study cohort included 140 men with metastatic prostate cancer at initial diagnosis. Metastatic sites were divided into 4 groups as follows: solitary bone, 2–4 bones, ≥5 bones, and visceral organs. Patient, tumor, and treatment characteristics, and clinical outcomes were compared between patients treated with (prostate radiotherapy [PRT] group) or without radiotherapy to the primary tumor. Results Patients in PRT group presented with a statistically significantly younger age (p = .02), whereas other characteristics showed no significant difference. Overall survival (OS) and biochemical failure-free survival (BCFFS) were improved in PRT patients (3-year OS: 69% vs. 43%, p = 0.004; 3-year BCFFS: 52% vs. 16%, p = 0.002). Multivariate analysis identified PRT as a significant predictor of both OS (hazard ratio [HR] = 0.43, p = 0.015). None of the 38 PRT patients experienced severe (grade ≥3) genitourinary or gastrointestinal toxicity. Conclusions Our data suggest that radiotherapy to the primary tumor was associated with improved OS and BCFFS in metastatic prostate cancer. The results of this study warrant prospective controlled clinical trials of this approach in stage IV prostate cancer patients with limited extent of bone metastasis and good performance status. PMID:26807740

Prostate Cancer Biorepository Network (PCBN)

DTIC Science & Technology

2017-10-01

Award Number: W81XWH-14-2-0183 TITLE: Prostate Cancer Biorepository Network (PCBN) PRINCIPAL INVESTIGATOR: Colm Morrissey CONTRACTING...1. REPORT DATE October 2017 2. REPORT TYPE Annual 3. DATES COVERED 09/30/2016 - 09/29/2017 4. TITLE AND SUBTITLE Prostate Cancer Biorepository...DISTRIBUTION / AVAILABILITY STATEMENT Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The Genitourinary Cancer

Opposing Effects of Cyclooxygenase-2 (COX-2) on Estrogen Receptor β (ERβ) Response to 5α-Reductase Inhibition in Prostate Epithelial Cells*

PubMed Central

Liu, Teresa T.; Grubisha, Melanie J.; Frahm, Krystle A.; Wendell, Stacy G.; Liu, Jiayan; Ricke, William A.; Auchus, Richard J.; DeFranco, Donald B.

2016-01-01

Current pharmacotherapies for symptomatic benign prostatic hyperplasia (BPH), an androgen receptor-driven, inflammatory disorder affecting elderly men, include 5α-reductase (5AR) inhibitors (i.e. dutasteride and finasteride) to block the conversion of testosterone to the more potent androgen receptor ligand dihydrotestosterone. Because dihydrotestosterone is the precursor for estrogen receptor β (ERβ) ligands, 5AR inhibitors could potentially limit ERβ activation, which maintains prostate tissue homeostasis. We have uncovered signaling pathways in BPH-derived prostate epithelial cells (BPH-1) that are impacted by 5AR inhibition. The induction of apoptosis and repression of the cell adhesion protein E-cadherin by the 5AR inhibitor dutasteride requires both ERβ and TGFβ. Dutasteride also induces cyclooxygenase type 2 (COX-2), which functions in a negative feedback loop in TGFβ and ERβ signaling pathways as evidenced by the potentiation of apoptosis induced by dutasteride or finasteride upon pharmacological inhibition or shRNA-mediated ablation of COX-2. Concurrently, COX-2 positively impacts ERβ action through its effect on the expression of a number of steroidogenic enzymes in the ERβ ligand metabolic pathway. Therefore, effective combination pharmacotherapies, which have included non-steroidal anti-inflammatory drugs, must take into account biochemical pathways affected by 5AR inhibition and opposing effects of COX-2 on the tissue-protective action of ERβ. PMID:27226548

Arctigenin in combination with quercetin synergistically enhances the antiproliferative effect in prostate cancer cells.

PubMed

Wang, Piwen; Phan, Tien; Gordon, David; Chung, Seyung; Henning, Susanne M; Vadgama, Jaydutt V

2015-02-01

We investigated whether a combination of two promising chemopreventive agents arctigenin (Arc) and quercetin (Q) increases the anticarcinogenic potency at lower concentrations than necessary when used individually in prostate cancer. Androgen-dependent LAPC-4 and LNCaP prostate cancer cells were treated with low doses of Arc and Q alone or in combination for 48 h. The antiproliferative activity of Arc was 10- to 20-fold stronger than Q in both cell lines. Their combination synergistically enhanced the antiproliferative effect, with a stronger effect in androgen receptor (AR) wild-type LAPC-4 cells than in AR mutated LNCaP cells. Arc demonstrated a strong ability to inhibit AR protein expression in LAPC-4 cells. The combination treatment significantly inhibited both AR and PI3K/Akt pathways compared to control. A protein array analysis revealed that the mixture targets multiple pathways particularly in LAPC-4 cells including Stat3 pathway. The mixture significantly inhibited the expression of several oncogenic microRNAs including miR-21, miR-19b, and miR-148a compared to control. The mixture also enhanced the inhibition of cell migration in both cell lines compared to individual compounds tested. The combination of Arc and Q that target similar pathways, at low physiological doses, provides a novel regimen with enhanced chemoprevention in prostate cancer. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Arctigenin in combination with quercetin synergistically enhances the anti-proliferative effect in prostate cancer cells

PubMed Central

Wang, Piwen; Phan, Tien; Gordon, David; Chung, Seyung; Henning, Susanne M.; Vadgama, Jaydutt V.

2014-01-01

Scope We investigated whether a combination of two promising chemopreventive agents arctigenin and quercetin increases the anti-carcinogenic potency at lower concentrations than necessary when used individually in prostate cancer. Methods and results Androgen-dependent LAPC-4 and LNCaP prostate cancer cells were treated with low doses of arctigenin and quercetin alone or in combination for 48h. The anti-proliferative activity of arctigenin was 10-20 fold stronger than quercetin in both cell lines. Their combination synergistically enhanced the anti-proliferative effect, with a stronger effect in androgen receptor (AR) wild-type LAPC-4 cells than in AR mutated LNCaP cells. Arctigenin demonstrated a strong ability to inhibit AR protein expression in LAPC-4 cells. The combination treatment significantly inhibited both AR and PI3K/Akt pathways compared to control. A protein array analysis revealed that the mixture targets multiple pathways particularly in LAPC-4 cells including Stat3 pathway. The mixture significantly inhibited the expression of several oncogenic microRNAs including miR-21, miR-19b, and miR-148a compared to control. The mixture also enhanced the inhibition of cell migration in both cell lines compared to individual compounds tested. Conclusion The combination of arctigenin and quercetin, that target similar pathways, at low physiological doses, provides a novel regimen with enhanced chemoprevention in prostate cancer. PMID:25380086

Phosphorus magnetic resonance spectroscopic imaging at 7 T in patients with prostate cancer.

PubMed

Lagemaat, Miriam W; Vos, Eline K; Maas, Marnix C; Bitz, Andreas K; Orzada, Stephan; van Uden, Mark J; Kobus, Thiele; Heerschap, Arend; Scheenen, Tom W J

2014-05-01

The aim of this study was to identify characteristics of phosphorus (P) spectra of the human prostate and to investigate changes of individual phospholipid metabolites in prostate cancer through in vivo P magnetic resonance spectroscopic imaging (MRSI) at 7 T. In this institutional review board-approved study, 15 patients with biopsy-proven prostate cancer underwent T2-weighted magnetic resonance imaging and 3-dimensional P MRSI at 7 T. Voxels were selected at the tumor location, in normal-appearing peripheral zone tissue, normal-appearing transition zone tissue, and in the base of the prostate close to the seminal vesicles. Phosphorus metabolite ratios were determined and compared between tissue types. Signals of phosphoethanolamine (PE) and phosphocholine (PC) were present and well resolved in most P spectra in the prostate. Glycerophosphocholine signals were observable in 43% of the voxels in malignant tissue, but in only 10% of the voxels in normal-appearing tissue away from the seminal vesicles. In many spectra, independent of tissue type, 2 peaks resonated in the chemical shift range of inorganic phosphate, possibly representing 2 separate pH compartments. The PC/PE ratio in the seminal vesicles was highly elevated compared with the prostate in 5 patients. A considerable overlap of P metabolite ratios was found between prostate cancer and normal-appearing prostate tissue, preventing direct discrimination of these tissues. The only 2 patients with high Gleason scores tumors (≥4+5) presented with high PC and glycerophosphocholine levels in their cancer lesions. Phosphorus MRSI at 7 T shows distinct features of phospholipid metabolites in the prostate gland and its surrounding structures. In this exploratory study, no differences in P metabolite ratios were observed between prostate cancer and normal-appearing prostate tissue possibly because of the partial volume effects of small tumor foci in large MRSI voxels.

Nine-year prostate cancer survival differences between aggressive versus conservative therapy in men with advanced and metastatic prostate cancer.

PubMed

Dall'Era, Marc A; Lo, Mary J; Chen, Jaclyn; Cress, Rosemary; Hamilton, Ann S

2018-05-01

To the authors' knowledge, the survival benefit of local therapy in the setting of advanced prostate cancer remains unknown. The authors investigated whether prostate-directed treatment with either surgery or radiotherapy versus conservative treatment in the setting of locally advanced or metastatic disease was associated with improved survival within a cohort of men from the Centers for Disease Control and Prevention's (CDC) Breast and Prostate Cancer Data Quality and Patterns of Care Study (CDC POC-BP). Men diagnosed with locally advanced (cT3-T4 or N+ and M0) or metastatic prostate cancer were identified. The authors compared survival by treatment type, categorized as conservative (androgen deprivation therapy only) versus aggressive (radical prostatectomy or any type of radiotherapy). Nine-year overall survival and prostate cancer-specific survival were estimated using the Kaplan-Meier method. The Cox proportional hazards model was used to determine factors independently associated with 9-year prostate cancer-specific survival. For men with advanced, nonmetastatic prostate cancer, conservative treatment alone was associated with a 4 times higher likelihood of prostate cancer mortality compared with men treated with surgery (hazard ratio, 4.18; 95% confidence interval, 1.44-12.14). In contrast, no difference was found between conservative versus aggressive treatment after adjusting for covariates for men with metastatic disease. The 9-year prostate cancer-specific survival rate was 27% for those receiving aggressive treatment versus 24% for men undergoing conservative treatment. The authors did not observe a survival advantage with local therapy in addition to standard androgen deprivation therapy for men with metastatic prostate cancer. However, the results of the current study did affirm advantages in the setting of locally advanced disease. Aggressive local therapy in the setting of metastatic disease needs to be studied carefully before clinical adoption. Cancer 2018;124:1921-8. © 2018 American Cancer Society. © 2018 American Cancer Society.

Expression and role of the angiotensin II AT2 receptor in human prostate tissue: in search of a new therapeutic option for prostate cancer.

PubMed

Guimond, Marie-Odile; Battista, Marie-Claude; Nikjouitavabi, Fatemeh; Carmel, Maude; Barres, Véronique; Doueik, Alexandre A; Fazli, Ladan; Gleave, Martin; Sabbagh, Robert; Gallo-Payet, Nicole

2013-07-01

Evidence shows that angiotensin II type 1 receptor (AT1R) blockers may be associated with improved outcome in prostate cancer patients. It has been proposed that part of this effect could be due to angiotensin II type 2 receptor (AT2R) activation, the only active angiotensin II receptor in this situation. This study aimed to characterize the localization and expression of AT2R in prostate tissues and to assess its role on cell morphology and number in prostatic epithelial cells in primary culture. AT2R and its AT2R-interacting protein (ATIP) expression were assessed on non-tumoral and tumoral human prostate using tissue microarray immunohistochemistry, binding assay, and Western blotting. AT2R effect on cell number was measured in primary cultures of epithelial cells from non-tumoral human prostate. AT2R was localized at the level of the acinar epithelial layer and its expression decreased in cancers with a Gleason score 6 or higher. In contrast, ATIP expression increased with cancer progression. Treatment of primary cell cultures from non-tumoral prostate tissues with C21/M024, a selective AT2R agonist, alone or in co-incubation with losartan, an AT1R antagonist, significantly decreased cell number compared to untreated cells. AT2R and ATIP are present in non-tumoral human prostate tissues and differentially regulated according to Gleason score. The decrease in non-tumoral prostate cell number upon selective AT2R stimulation suggests that AT2R may have a protective role against prostate cancer development. Treatment with a selective AT2R agonist could represent a new approach for prostate cancer prevention or for patients on active surveillance. Copyright © 2013 Wiley Periodicals, Inc.

Re-epithelialization resulted from prostate basal cells in canine prostatic urethra may represent the ideal healing method after two-micron laser resection of the prostate

PubMed Central

Cao, Ying; Luo, Guang-Heng; Luo, Lei; Yang, Xiu-Shu; Hu, Jian-Xin; Shi, Hua; Huang, Ping; Sun, Zhao-Lin; Xia, Shu-Jie

2015-01-01

The purpose of this study is to characterize the re-epithelialization of wound healing in canine prostatic urethra and to evaluate the effect of this re-epithelialization way after two-micron laser resection of the prostate (TmLRP). TmLRP and partial bladder neck mucosa were performed in 15 healthy adult male crossbred canines. Wound specimens were harvested at 3 days, and 1, 2, 3, and 4 weeks after operation, respectively. The histopathologic characteristics were observed by hematoxylin and eosin staining. The expression of cytokeratin 14 (CK14), CK5, CK18, synaptophysin (Syn), chromogranin A (CgA), uroplakin, transforming growth factor-β1(TGF-β1), and TGF-β type II receptor in prostatic urethra wound were examined by immunohistochemistry and real-time polymerase chain reaction, respectively. Van Gieson staining was performed to determine the expression of collagen fibers in prostatic urethra and bladder neck would. The results showed that the re-epithelialization of the prostatic urethra resulted from the mobilization of proliferating epithelial cells from residual prostate tissue under the wound. The proliferating cells expressed CK14, CK5, but not CK18, Syn, and CgA and re-epithelialize expressed uroplakin since 3 weeks. There were enhanced TGF-β1 and TGF-β type II receptor expression in proliferating cells and regenerated cells, which correlated with specific phases of re-epithelialization. Compared with the re-epithelialization of the bladder neck, re-epithelialization of canine prostatic urethra was faster, and the expression of collagen fibers was relatively low. In conclusion, re-epithelialization in canine prostatic urethra resulted from prostate basal cells after TmLRP and this re-epithelialization way may represent the ideal healing method from anatomic repair to functional recovery after injury. PMID:25652631

Real time MRI prostate segmentation based on wavelet multiscale products flow tracking.

PubMed

Flores-Tapia, Daniel; Venugopal, Niranjan; Thomas, Gabriel; McCurdy, Boyd; Ryner, Lawrence; Pistorius, Stephen

2010-01-01

Currently, prostate cancer is the third leading cause of cancer-related deaths among men in North America. As with many others types of cancer, early detection and treatment greatly increases the patient's chance of survival. Combined Magnetic Resonance Imaging and Spectroscopic Imaging (MRI/MRSI) techniques have became a reliable tool for early stage prostate cancer detection. Nevertheless, their performance is strongly affected by the determination of the region of interest (ROI) prior to data acquisition process. The process of executing prostate MRI/MRSI techniques can be significantly enhanced by segmenting the whole prostate. A novel method for segmentation of the prostate in MRI datasets is presented. This method exploits the different behavior presented by signal singularities and noise in the wavelet domain in order to accurately detect the borders around the prostate. The prostate contour is then traced by using a set of spatially variant rules that are based on prior knowledge about the general shape of the prostate. The proposed method yielded promising results when applied to clinical datasets.

The microbiome in prostate inflammation and prostate cancer.

PubMed

Porter, Corey M; Shrestha, Eva; Peiffer, Lauren B; Sfanos, Karen S

2018-05-23

The human microbiome may influence prostate cancer initiation and/or progression through both direct and indirect interactions. To date, the majority of studies have focused on direct interactions including the influence of prostate infections on prostate cancer risk and, more recently, on the composition of the urinary microbiome in relation to prostate cancer. Less well understood are indirect interactions of the microbiome with prostate cancer, such as the influence of the gastrointestinal or oral microbiota on pro- or anti-carcinogenic xenobiotic metabolism, and treatment response. We review the literature to date on direct and indirect interactions of the microbiome with prostate inflammation and prostate cancer. Emerging studies indicate that the microbiome can influence prostate inflammation in relation to benign prostate conditions such as prostatitis/chronic pelvic pain syndrome and benign prostatic hyperplasia, as well as in prostate cancer. We provide evidence that the human microbiome present at multiple anatomic sites (urinary tract, gastrointestinal tract, oral cavity, etc.) may play an important role in prostate health and disease. In health, the microbiome encourages homeostasis and helps educate the immune system. In dysbiosis, a systemic inflammatory state may be induced, predisposing remote anatomical sites to disease, including cancer. The microbiome's ability to affect systemic hormone levels may also be important, particularly in a disease such as prostate cancer that is dually affected by estrogen and androgen levels. Due to the complexity of the potential interconnectedness between prostate cancer and the microbiome, it is vital to further explore and understand the relationships that are involved.

Cdc20/p55 mediates the resistance to docetaxel in castration-resistant prostate cancer in a Bim-dependent manner.

PubMed

Wu, Fei; Lin, Yun; Cui, Peng; Li, Hongyun; Zhang, Lechao; Sun, Zeqiang; Huang, Shengliang; Li, Shun; Huang, Shiming; Zhao, Qingli; Liu, Qingyong

2018-06-01

At least to date, no effective treatment for advanced castration-resistant prostate cancer (CRPC) has been established. Recent studies indicated that cell division cycle 20 homolog (Cdc20) overexpression is associated with poor prognosis in patients with castration-resistant prostate cancer. However, the mechanism of Cdc20 in the development of docetaxel resistance in CRPC remains elusive. In this study, the transcription of Cdc20 was confirmed in three independent CRPC cell lines derived from different tissues, including LNCaP, PC3, and DU145. Docetaxel resistant (DR) cell lines were generated within the background of DU145 and PC3. The protein levels of Cdc20 and the biological phenotype were detected in both wild-type and DR cell lines. To further explore the mechanism of Cdc20 overexpression, stable cell lines with Cdc20 or Bcl-2 interacting mediator of cell death (Bim) deprivation were generated and examined for biological parameters. In addition, a specific Cdc20 inhibitor was used in DR cell lines to explore the potential solution for docetaxel resistant CRPC. Here, we identified Cdc20 is overexpressed in docetaxel resistant CRPC cell lines, including LNCaP, PC3, and DU145. We also reported that DR cell lines, which mimic the recurrent prostate cancer cells after docetaxel treatment, have higher levels of Cdc20 protein compared with the CRPC cell lines. Interestingly, the protein levels of Bim, an E3 ligase substrate of Cdc20, were decreased in DR cell lines compared with the wild-type, while the mRNA levels were similar. More importantly, in DR cell lines, the biological phenotype induced by Cdc20 deletion could be significantly reversed by the additional knockdown of Bim. As a result, docetaxel resistant prostate cancer cells treated with the pharmacological Cdc20 inhibitor became sensitive to docetaxel treatment. In conclusion, our data collectively demonstrated that Cdc20 overexpression facilitates the docetaxel resistant of the CRPC cell lines in a Bim-dependent manner. Furthermore, additionally targeting Cdc20 might be a promising solution for the treatment of the CRPC with docetaxel resistance.

Benign Prostatic Hyperplasia (BPH)

MedlinePlus

... Benign prostatic hyperplasia (BPH) — also called prostate gland enlargement — is a common condition as men get older. ... There are several effective treatments for prostate gland enlargement, including medications, minimally invasive therapies and surgery. To ...

Barriers and facilitators of prostate cancer screening among Filipino men in Hawaii.

PubMed

Conde, Francisco A; Landier, Wendy; Ishida, Dianne; Bell, Rose; Cuaresma, Charlene F; Misola, Jane

2011-03-01

To examine perceptions, attitudes, and beliefs regarding barriers and facilitators to prostate cancer screening, and to identify potential interventional strategies to promote prostate cancer screening among Filipino men in Hawaii. Exploratory, qualitative. Community-based settings in Hawaii. 20 Filipino men age 40 years or older. Focus group discussions were tape recorded and transcribed, and content analysis was performed for emergent themes. Perceptions regarding prostate cancer, barriers and facilitators to prostate cancer screening, and culturally relevant interventional strategies. Perceptions of prostate cancer included fatalism, hopelessness, and dread. Misconceptions regarding causes of prostate cancer, such as frequency of sexual activity, were identified. Barriers to prostate cancer screening included lack of awareness of the need for screening, reticence to seek health care when feeling well, fear of cancer diagnosis, financial issues, time constraints, and embarrassment. Presence of urinary symptoms, personal experience with family or friends who had cancer, and receiving recommendations from a healthcare provider regarding screening were facilitators for screening. Potential culturally relevant interventional strategies to promote prostate cancer screening included screening recommendations from healthcare professionals and cancer survivors; radio or television commercials and newspaper articles targeting the Filipino community; informational brochures in Tagalog, Ilocano, or English; and interactive, educational forums facilitated by multilingual Filipino male healthcare professionals. Culturally relevant interventions are needed that address barriers to prostate cancer screening participation and misconceptions about causes of prostate cancer. Findings provide a foundation for future research regarding development of interventional strategies to promote prostate cancer screening among Filipino men.

Mortality and prostate cancer risk in 19,598 men after surgery for benign prostatic hyperplasia.

PubMed

Holman, C D; Wisniewski, Z S; Semmens, J B; Rouse, I L; Bass, A J

1999-07-01

To examine postoperative mortality and prostate cancer risk after the first prostatectomy for benign prostatic hypertrophy over a 17-year period in a population-based cohort of men in Western Australia, using improved methods to adjust for comorbidity. The relative survival from death and prostate cancer incidence was calculated against the background population rates. The outcomes of transurethral resection of the prostate (TURP) and open prostatectomy (OP) were compared adjusting for calendar year, age, admission type and comorbidity using Cox regression. Fractional polynomials were used to take account of nonlinearity in confounder effects. At 10 years, the relative survival was 116.5% in TURP patients and 123.5% after OP. Adjusting only for confounding by age, calendar year and admission type, TURP had a higher mortality rate than OP (rate ratio, RR, 1. 20; 95% confidence interval 1.08-1.34). The RR fell to 1.10 (0.99-1. 23) after adjustment for comorbidity and to 1.07 (0.95-1.19) when accounting for nonlinearity. The relative survival from the incidence of prostate cancer at 10 years was 103.7% after TURP and 104.5% after OP. The RR adjusted for age and calendar year was 1.44 (0.94-2.21) for incidence and 1.37 (0.81-2.29) for prostate cancer mortality. There is at most a small and clinically unimportant excess mortality risk from TURP; any difference could be due to a protective effect of OP on the long-term risk of prostate cancer and a lower rate of repeat prostatectomy.

Metabolomic signatures of aggressive prostate cancer.

PubMed

McDunn, Jonathan E; Li, Zhen; Adam, Klaus-Peter; Neri, Bruce P; Wolfert, Robert L; Milburn, Michael V; Lotan, Yair; Wheeler, Thomas M

2013-10-01

Current diagnostic techniques have increased the detection of prostate cancer; however, these tools inadequately stratify patients to minimize mortality. Recent studies have identified a biochemical signature of prostate cancer metastasis, including increased sarcosine abundance. This study examined the association of tissue metabolites with other clinically significant findings. A state of the art metabolomics platform analyzed prostatectomy tissues (331 prostate tumor, 178 cancer-free prostate tissues) from two independent sites. Biochemicals were analyzed by gas chromatography-mass spectrometry and ultrahigh performance liquid chromatography-tandem mass spectrometry. Statistical analyses identified metabolites associated with cancer aggressiveness: Gleason score, extracapsular extension, and seminal vesicle and lymph node involvement. Prostate tumors had significantly altered metabolite profiles compared to cancer-free prostate tissues, including biochemicals associated with cell growth, energetics, stress, and loss of prostate-specific biochemistry. Many metabolites were further associated with clinical findings of aggressive disease. Aggressiveness-associated metabolites stratified prostate tumor tissues with high abundances of compounds associated with normal prostate function (e.g., citrate and polyamines) from more clinically advanced prostate tumors. These aggressive prostate tumors were further subdivided by abundance profiles of metabolites including NAD+ and kynurenine. When added to multiparametric nomograms, metabolites improved prediction of organ confinement (AUROC from 0.53 to 0.62) and 5-year recurrence (AUROC from 0.53 to 0.64). These findings support and extend earlier metabolomic studies in prostate cancer and studies where metabolic enzymes have been associated with carcinogenesis and/or outcome. Furthermore, these data suggest that panels of analytes may be valuable to translate metabolomic findings to clinically useful diagnostic tests. Copyright © 2013 Wiley Periodicals, Inc.

Evaluation of the resistive index of prostatic blood flow in benign prostatic hyperplasia.

PubMed

Abdelwahab, Osama; El-Barky, Ehab; Khalil, Mostafa Mahmoud; Kamar, Ahmad

2012-01-01

The aim of this work is to study the resistive index (RI) of prostatic blood flow by transrectal power Doppler sonography in benign prostatic hyperplasia (BPH) to determine its correlation with other parameters of BPH. Eighty-two male patients aged 52-86 years with lower urinary tract symptoms (LUTS) due to BPH were included in the study. Patients with prostate cancer, neurogenic bladder, or with other pathology (e.g. prostatitis, bladder stone) were excluded from the study. All patients were evaluated by full history including Internatinoal Prostate Symptoms Score (IPSS), general and local examination (DRE), neurologic examination, uroflowmetry, laboratory investigations including urine analysis, routine laboratory tests and serum prostate specific antigen (PSA). Transrectal ultrasonography was used to calculate the total prostatic volume. Transrectal Power Doppler Ultrasound (PUD) was used to identify the capsular and urethral arteries of the prostate and to measures the RI value. The mean prostate volume was 75.1 ± 44.7 g. The mean RI of the right and left capsular arteries were 0.76 ± 0.06 and 0.76 ± 0.07, respectively. The mean RI of the urethral arteries was 0.76 ± 0.08. There was a high significative correlation between the increase of the RI of the right and left capsular and urethral arteries and the degree of obstruction (P value < 0.001), severity of symptoms (P value < 0.001) and also the prostatic volume (P value < 0.001). Resistive index of the prostatic blood flow can be applied as an easy and non-invasive tool to evaluate the lower urinary tract obstruction due to BPH.

Advanced Prostate Cancer

MedlinePlus

... to learn about these types of treatments. This article is for men with metastatic and castrate-resistant ... Related Resources Urology 101 Fact Sheet UrologyHealth extra® Articles What is Advanced Prostate Cancer? Keeping Your Bones ...

Investigation of a Putative Estrogen-Imprinting Gene, Phosphodiesterase Type IV Variant (PDE4D4), in Determining Prostate Cancer Risk

DTIC Science & Technology

2007-04-01

ductal prostate adenocarcinomas in NBL / Cr and Sprague-Dawley Hsd:SD rats treated with a combination of testosterone and estradiol-17h or...Androl 1981;2(6):293–9. 80] Bosland MC, Ford H, Horton L. Induction at high incidence of ductal prostate adenocarcinomas in NBL /Cr and Sprague–Dawley

Intrinsic BET inhibitor resistance in SPOP-mutated prostate cancer is mediated by BET protein stabilization and AKT-mTORC1 activation.

PubMed

Zhang, Pingzhao; Wang, Dejie; Zhao, Yu; Ren, Shancheng; Gao, Kun; Ye, Zhenqing; Wang, Shangqian; Pan, Chun-Wu; Zhu, Yasheng; Yan, Yuqian; Yang, Yinhui; Wu, Di; He, Yundong; Zhang, Jun; Lu, Daru; Liu, Xiuping; Yu, Long; Zhao, Shimin; Li, Yao; Lin, Dong; Wang, Yuzhuo; Wang, Liguo; Chen, Yu; Sun, Yinghao; Wang, Chenji; Huang, Haojie

2017-09-01

Bromodomain and extraterminal domain (BET) protein inhibitors are emerging as promising anticancer therapies. The gene encoding the E3 ubiquitin ligase substrate-binding adaptor speckle-type POZ protein (SPOP) is the most frequently mutated in primary prostate cancer. Here we demonstrate that wild-type SPOP binds to and induces ubiquitination and proteasomal degradation of BET proteins (BRD2, BRD3 and BRD4) by recognizing a degron motif common among them. In contrast, prostate cancer-associated SPOP mutants show impaired binding to BET proteins, resulting in decreased proteasomal degradation and accumulation of these proteins in prostate cancer cell lines and patient specimens and causing resistance to BET inhibitors. Transcriptome and BRD4 cistrome analyses reveal enhanced expression of the GTPase RAC1 and cholesterol-biosynthesis-associated genes together with activation of AKT-mTORC1 signaling as a consequence of BRD4 stabilization. Our data show that resistance to BET inhibitors in SPOP-mutant prostate cancer can be overcome by combination with AKT inhibitors and further support the evaluation of SPOP mutations as biomarkers to guide BET-inhibitor-oriented therapy in patients with prostate cancer.

A Content Analysis of YouTubeTM Videos Related to Prostate Cancer.

PubMed

Basch, Corey H; Menafro, Anthony; Mongiovi, Jennifer; Hillyer, Grace Clarke; Basch, Charles E

2016-09-29

In the United States, prostate cancer is the most common type of cancer in men after skin cancer. There is a paucity of research devoted to the types of prostate cancer information available on social media outlets. YouTube TM is a widely used video sharing website, which is emerging as commonplace for information related to health. The purpose of this study was to describe the most widely viewed YouTube TM videos related to prostate cancer. The 100 videos were watched a total of 50,278,770 times. The majority of videos were uploaded by consumers (45.0%) and medical or government professionals (30%). The purpose of most videos (78.0%) was to provide information, followed by discussions of prostate cancer treatment (51%) and prostate-specific antigen testing and routine screening (26%). All videos uploaded by medical and government professionals and 93.8% of videos uploaded by news sources provided information compared with about two thirds of consumer and less than one half of commercial and advertisement videos (p < .001). As society becomes increasingly technology-based, there is a need to help consumers acquire knowledge and skills to identify credible information to help inform their decisions. © The Author(s) 2016.

Race and Survival Following Brachytherapy-Based Treatment for Men With Localized or Locally Advanced Adenocarcinoma of the Prostate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Winkfield, Karen M., E-mail: kwinkfield@partners.org; Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts; Chen Minghui

2011-11-15

Purpose: We investigated whether race was associated with risk of death following brachytherapy-based treatment for localized prostate cancer, adjusting for age, cardiovascular comorbidity, treatment, and established prostate cancer prognostic factors. Methods: The study cohort was composed of 5,360 men with clinical stage T1-3N0M0 prostate cancer who underwent brachytherapy-based treatment at 20 centers within the 21st Century Oncology consortium. Cox regression multivariable analysis was used to evaluate the risk of death in African-American and Hispanic men compared to that in Caucasian men, adjusting for age, pretreatment prostate-specific antigen (PSA) level, Gleason score, clinical T stage, year and type of treatment, medianmore » income, and cardiovascular comorbidities. Results: After a median follow-up of 3 years, there were 673 deaths. African-American and Hispanic races were significantly associated with an increased risk of all-cause mortality (ACM) (adjusted hazard ratio, 1.77 and 1.79; 95% confidence intervals, 1.3-2.5 and 1.2-2.7; p < 0.001 and p = 0.005, respectively). Other factors significantly associated with an increased risk of death included age (p < 0.001), Gleason score of 8 to 10 (p = 0.04), year of brachytherapy (p < 0.001), and history of myocardial infarction treated with stent or coronary artery bypass graft (p < 0.001). Conclusions: After adjustment for prostate cancer prognostic factors, age, income level, and revascularized cardiovascular comorbidities, African-American and Hispanic races were associated with higher ACM in men with prostate cancer. Additional causative factors need to be identified.« less

Polygamy, sexual behavior in a population under risk for prostate cancer diagnostic: an observational study from the Black Sea Region in Turkey.

PubMed

Cirakoglu, Abdullah; Benli, Erdal; Yuce, Ahmet

2018-03-23

Although prostate cancer (PCa) is the most common cancer type in men, a replaceable risk factor has not yet been established. In our study, we assessed the relationship between the number of sexual partners, age of first sexual experience and age of first masturbation and prostate cancer incidence. In Ordu University Department of Urology between January 2013 and September 2016, in PSA elevation and rectal examination, patients with prostate biopsy were evaluated due to nodule palpation in the prostate. At younger ages and at present, their first masturbation ages, first sexual debut ages, and total sexual partner numbers were recorded. The correlation between the obtained data and PCa frequency was evaluated. The study included 146 patients with PCa identified on biopsy and 171 patients with benign biopsy results who answered the questions. 66.7% of the ones whose biopsy results were benign and 40.6% of cancer suspects had only one sexual partner. The median number of sexual partners was 1±4 (1-100) in the benign group and 2±6 (1-500) in the malignant group (p=0.039). There was a negative correlation between age of first sexual debut and number of partners (r: -0,479; p<0.001). In our study, it appears that there may be an association between the number of sexual partners and prostate cancer in the patient group with PSA level above 4ng/mL. Avoidance of sexual promiscuity or participation in protected sex may be beneficial to protect against prostate cancer. Copyright® by the International Brazilian Journal of Urology.

Quantification of Mesenchymal Stem Cells (MSCs) at sites of human prostate cancer.

PubMed

Brennen, W Nathaniel; Chen, Shuangling; Denmeade, Samuel R; Isaacs, John T

2013-01-01

Circulating bone marrow-derived Mesenchymal Stem Cells (BM-MSCs) have an innate tropism for tumor tissue in response to the inflammatory microenvironment present in malignant lesions. The prostate is bombarded by numerous infectious and inflammatory insults over a lifetime. Chronic inflammation is associated with CXCL12, CCL5, and CCL2, which are highly overexpressed in prostate cancer. Among other cell types, these chemoattractant stimuli recruit BM-MSCs to the tumor. MSCs are minimally defined as plastic-adhering cells characterized by the expression of CD90, CD73, and CD105 in the absence of hematopoietic markers, which can differentiate into osteoblasts, chondrocytes, and adipocytes. MSCs are immunoprivileged and have been implicated in tumorigenesis through multiple mechanisms, including promoting proliferation, angiogenesis, and metastasis, in addition to the generation of an immunosuppressive microenvironment. We have demonstrated that MSCs represent 0.01-1.1% of the total cells present in core biopsies from primary human prostatectomies. Importantly, these analyses were performed on samples prior to expansion in tissue culture. MSCs in these prostatectomy samples are FAP-, CD90-, CD73-, and CD105-positive, and CD14-, CD20-, CD34-, CD45-, and HLA-DR-negative. Additionally, like BM-MSCs, these prostate cancer-derived stromal cells (PrCSCs) were shown to differentiate into osteoblasts, adipocytes and chondrocytes. In contrast to primary prostate cancer-derived epithelial cells, fluorescently-labeled PrCSCs and BM-MSCs were both shown to home to CWR22RH prostate cancer xenografts following IV injection. These studies demonstrate that not only are MSCs present in sites of prostate cancer where they may contribute to carcinogenesis, but these cells may also potentially be used to deliver cytotoxic or imaging agents for therapeutic and/or diagnostic purposes.

Dihydrotestosterone in prostatic hypertrophy

PubMed Central

Siiteri, Pentti K.; Wilson, Jean D.

1970-01-01

To explore the relation between androgens and prostatic hypertrophy in man, the concentrations of testosterone, dihydrotestosterone, and androstenedione and the rate of conversion of testosterone to dihydrotestosterone have been measured in normal and hypertrophic prostate tissue. First, a double isotope derivative technique was adapted for the measurement of tissue androgen content in 15 normal and 10 hypertrophic prostates. Although there was no significant difference in the content of androstenedione and testosterone between the two types of tissue, the content of dihydrotestosterone was significantly greater in the hypertrophic tissue (0.60 ±0.10 μg/100 g) than in the normal glands (0.13 ±0.05 μg/100 g). Second, a regional study was performed in three normal prostates and four glands with early hypertrophy, and it was demonstrated that the dihydrotestosterone content was two and three fold greater in the periurethral area where prostatic hypertrophy usually commences than in the outer regions of the gland. Finally, the rate of conversion of testosterone to dihydrotestosterone has been measured under standardized conditions in tissue slices from 4 normal and 20 hypertrophic prostates. There was no significant difference in the rate of dihydrotestosterone formation between the two types of gland (6.0 ±0.8 and 7.8 ±0.5 μμmoles/15 mg of tissue per hr). While the mechanism by which dihydrotestosterone accumulation occurs remains unexplained, it is possible that the local accumulation of dihydrotestosterone may be involved in the pathogenesis of prostatic hypertrophy in man. Images PMID:4194768

Impact of Prostate Inflammation on Lesion Development in the POET3+Pten+/− Mouse Model of Prostate Carcinogenesis

PubMed Central

Burcham, Grant N.; Cresswell, Gregory M.; Snyder, Paul W.; Chen, Long; Liu, Xiaoqi; Crist, Scott A.; Henry, Michael D.; Ratliff, Timothy L.

2015-01-01

Evidence linking prostatitis and prostate cancer development is contradictory. To study this link, the POET3 mouse, an inducible model of prostatitis, was crossed with a Pten-loss model of prostate cancer (Pten+/−) containing the ROSA26 luciferase allele to monitor prostate size. Prostatitis was induced, and prostate bioluminescence was tracked over 12 months, with lesion development, inflammation, and cytokine expression analyzed at 4, 8, and 12 months and compared with mice without induction of prostatitis. Acute prostatitis led to more proliferative epithelium and enhanced bioluminescence. However, 4 months after initiation of prostatitis, mice with induced inflammation had lower grade pre-neoplastic lesions. A trend existed toward greater development of carcinoma 12 months after induction of inflammation, including one of two mice with carcinoma developing perineural invasion. Two of 18 mice at the later time points developed lesions with similarities to proliferative inflammatory atrophy, including one mouse with associated carcinoma. Pten+/− mice developed spontaneous inflammation, and prostatitis was similar among groups of mice at 8 and 12 months. Analyzed as one cohort, lesion number and grade were positively correlated with prostatitis. Specifically, amounts of CD11b+Gr1+ cells were correlated with lesion development. These results support the hypothesis that myeloid-based inflammation is associated with lesion development in the murine prostate, and previous bouts of CD8-driven prostatitis may promote invasion in the Pten+/− model of cancer. PMID:25455686

Impact of poor glycemic control of type 2 diabetes mellitus on serum prostate-specific antigen concentrations in men.

PubMed

Atalay, Hasan Anıl; Akarsu, Murat; Canat, Lutfi; Ülker, Volkan; Alkan, İlter; Ozkuvancı, Unsal

2017-09-01

To evaluate the impact of poor glycemic control of type 2 diabetes mellitus (T2DM) on serum prostate-specific antigen (PSA) concentrations in men. We performed a prospective analysis of 215 consecutive patients affected by erectile dysfunction (ED). ED was evaluated using the IIEF-5 questionnaire and the poor glycemic control (PGC) of T2DM was assessed according to the HbA1c criteria (International Diabetes Federation). Patients were divided into PGC group (HbA1c ≥ 7%) and control group (CG) (HbA1c < 6%). Correlations between serum HbA1c levels and various variables were evaluated and multivariate logistic regression analyses were carried out to identify variables for PGC. We compared 110 cases to 105 controls men ranging from 44 to 81 years of age, lower PSA concentrations were observed in men with PGC (PGC mean PSA: 0.9 ng/dl, CG mean PSA: 2.1 ng/dl, p < 0.001). Also mean prostate volume was 60% was smaller among men with PGC compared with men with CG (PGC mean prostate volume: 26 ml, CG prostate volume: 43 ml, p < 0.001). A strong negative correlation was found between serum HbA1c levels and serum PSA (p < 0.001 and r = -0.665) concentrations in men with PGC. We also found at the multivariate logistic regression model that PSA, prostate volume and peak systolic velocity were independent predictors of PGC. Our results suggest that there is significant impact of PGC on serum PSA levels in T2DM. Poor glycemic control of type 2 diabetes was associated with lower serum PSA levels and smaller prostate volumes.

Prediagnostic prostate-specific antigen kinetics and the risk of biopsy progression in active surveillance patients.

PubMed

Iremashvili, Viacheslav; Barney, Shane L; Manoharan, Murugesan; Kava, Bruce R; Parekh, Dipen J; Punnen, Sanoj

2016-04-01

To analyze the association between prediagnostic prostate-specific antigen kinetics and the risk of biopsy progression in prostate cancer patients on active surveillance, and to study the effect of prediagnostic prostate-specific antigen values on the predictive performance of prostate-specific antigen velocity and prostate-specific antigen doubling time. The study included 137 active surveillance patients with two or more prediagnostic prostate-specific antigen levels measured over a period of at least 3 months. Two sets of analyses were carried out. First, the association between prostate-specific antigen kinetics calculated using only the prediagnostic prostate-specific antigen values and the risk of biopsy progression was studied. Second, using the same cohort of patients, the predictive value of prostate-specific antigen kinetics calculated using only post-diagnostic prostate-specific antigens and compared with that of prostate-specific antigen kinetics based on both pre- and post-diagnostic prostate-specific antigen levels was analyzed. Of 137 patients included in the analysis, 37 (27%) had biopsy progression over a median follow-up period of 3.2 years. Prediagnostic prostate-specific antigen velocity of more than 2 ng/mL/year and 3 ng/mL/year was statistically significantly associated with the risk of future biopsy progression. However, after adjustment for baseline prostate-specific antigen density, these associations were no longer significant. None of the tested prostate-specific antigen kinetics based on combined pre- and post-diagnostic prostate-specific antigen values were statistically significantly associated with the risk of biopsy progression. Historical prediagnostic prostate-specific antigens seems to be not clinically useful in patients diagnosed with low-risk prostate cancer on active surveillance. © 2016 The Japanese Urological Association.

Targeting chemokine (C-C motif) ligand 2 (CCL2) as an example of translation of cancer molecular biology to the clinic.

PubMed

Zhang, Jian; Patel, Lalit; Pienta, Kenneth J

2010-01-01

Chemokines are a family of small and secreted proteins that play pleiotropic roles in inflammation-related pathological diseases, including cancer. Among the identified 50 human chemokines, chemokine (C-C motif) ligand 2 (CCL2) is of particular importance in cancer development since it serves as one of the key mediators of interactions between tumor and host cells. CCL2 is produced by cancer cells and multiple different host cells within the tumor microenvironment. CCL2 mediates tumorigenesis in many different cancer types. For example, CCL2 has been reported to promote prostate cancer cell proliferation, migration, invasion, and survival, via binding to its functional receptor CCR2. Furthermore, CCL2 induces the recruitment of macrophages and induces angiogenesis and matrix remodeling. Targeting CCL2 has been demonstrated as an effective therapeutic approach in preclinical prostate cancer models, and currently, neutralizing monoclonal antibody against CCL2 has entered into clinical trials in prostate cancer. In this chapter, targeting CCL2 in prostate cancer will be used as an example to show translation of laboratory findings from cancer molecular biology to the clinic. Copyright © 2010 Elsevier Inc. All rights reserved.

T CELLS LOCALIZED TO THE ANDROGEN-DEPRIVED PROSTATE ARE TH1 AND TH17 BIASED

PubMed Central

Morse, Matthew D.; McNeel, Douglas G.

2013-01-01

BACKGROUND T cells infiltrate the prostates of prostate cancer patients undergoing neoadjuvant androgen deprivation. These prostate-infiltrating T cells have an oligoclonal phenotype, suggesting the development of an antigen-specific T-cell response. We hypothesized that androgen deprivation might elicit a prostate tissue-specific T-cell response that could potentially be combined with other immune-active therapies, and consequently sought to investigate the nature and timing of this T-cell response following castration. METHODS We investigated the phenotype and cytokine expression of T cells at various time points in the prostates of Lewis rats following surgical castration, and used adoptive transfer of prostate-infiltrating lymphocytes to determine whether the infiltration by T cells was mediated by effects of castration on the prostate or lymphocytes. RESULTS Prostate T-cell infiltration shortly after castration was TH1 biased up to approximately 30 days, followed by a predominance of TH17-type cells, which persisted until at least 90 days post castration. Prostate-infiltrating lymphocytes from sham-treated or castrate rats localized to the prostates of castrate animals. CONCLUSIONS These observations suggest castration elicits a time-dependent prostate-specific T-cell infiltration, and this infiltration is likely mediated by effects of castration on prostate tissue rather than T cells. These findings have implications for the timing of immunotherapies combined with androgen deprivation as treatments for prostate cancer. PMID:22213030

IL-17 is not essential for inflammation and chronic pelvic pain development in an experimental model of chronic prostatitis/chronic pelvic pain syndrome.

PubMed

Motrich, Ruben D; Breser, María L; Sánchez, Leonardo R; Godoy, Gloria J; Prinz, Immo; Rivero, Virginia E

2016-03-01

Pain and inflammation in the absence of infection are hallmarks in chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS) patients. The etiology of CP/CPPS is unclear, and autoimmunity has been proposed as a cause. Experimental autoimmune prostatitis (EAP) models have long been used for studying CP/CPPS. Herein, we studied prostate inflammation induction and chronic pelvic pain development in EAP using IL-12p40-KO, IL-4-KO, IL-17-KO, and wild-type (C57BL/6) mice. Prostate antigen (PAg) immunization in C57BL/6 mice induced specific Th1 and Th17 immune responses and severe prostate inflammation and cell infiltration, mainly composed of CD4 T cells and macrophages. Moreover, chronic pelvic pain was evidenced by increased allodynia responses. In immunized IL-17-KO mice, the presence of a prominent PAg-specific Th1 immune response caused similar prostate inflammation and chronic pelvic pain. Furthermore, markedly high PAg-specific Th1 immune responses, exacerbated prostate inflammation, and chronic pelvic pain were detected in immunized IL-4-KO mice. Conversely, immunized IL-12p40-KO mice developed PAg-specific Th2 immune responses, characterized by high IL-4 secretion and neither infiltration nor damage in the prostate. As observed in wild-type control animals, IL12p40-KO mice did not evidence tactile allodynia responses. Our results suggest that, as in patients, chronic pelvic pain is a consequence of prostate inflammation. After PAg immunization, a Th1-associated immune response develops and induces prostate inflammation and chronic pelvic pain. The absence of Th1 or Th2 cytokines, respectively, diminishes or enhances EAP susceptibility. In addition, IL-17 showed not to be essential for pathology induction and chronic pelvic pain development.

A Younger Man With Localized Prostate Cancer Asks, "Which Type of Radiation Is Right for Me?"

PubMed

Bekelman, Justin E

2018-06-20

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 61-year-old man presents with stage II prostate cancer after a period of active surveillance. Work-up reveals T1cN0M0 carcinoma, a prostate-specific antigen (PSA) level of 4.8 ng/mL, and Grade Group II (highest Gleason 3+4) in three cores of 12 taken, at the right mid-gland and right apex. The patient has been on active surveillance for the past 16 months. He was originally diagnosed after biopsy for an elevated PSA with stage I prostate cancer, T1cN0M0; PSA, 4.5 ng/mL; Grade Group 1 (Gleason 3+3) in one core of 12 taken, also at the right mid-gland. A multiparametric magnetic resonance imaging scan showed a heterogeneous peripheral zone without a dominant lesion and a calculated prostate volume of 28 mL. His medical history includes hypercholesterolemia, for which he takes atorvastatin. He is otherwise healthy and has no other significant medical or surgical history. His father had prostate cancer in his 70s and died of other causes at 89 years of age. The patient reports 2- to 3-hour urinary frequency and 0 to 1 nocturia, and has no difficulty obtaining or maintaining an erection. After meeting with his urologist, he sees a radiation oncologist.

A Study of the Frequency and Social Determinants of Exposure to Cancer-Related Direct-to-Consumer Advertising Among Breast, Prostate, and Colorectal Cancer Patients

PubMed Central

Tan, Andy SL

2014-01-01

Cancer-related direct-to-consumer advertising (DTCA) is controversial because cancer treatment is complex and entails more risks and costs than typical treatments that are advertised for other conditions. Drawing from the Structural Influence Model of Communication, this study explores communication inequalities in DTCA exposure across social determinants among a population-based sample of 2013 patients diagnosed with breast, prostate, or colorectal cancers. Three survey items assessed patients' frequency of encountering ads concerning treatment alternatives for cancer, dealing with side effects of treatment, and doctors or hospitals offering services for cancer following their diagnosis. The analysis showed that overall exposure to DTCA in this study population was modest (median was once per week). Breast cancer patients reported significantly higher exposure to all three ad categories and overall DTCA exposure than prostate and colorectal cancer patients. Older patients consistently reported lower overall exposure to DTCA across the three cancer types. Other significant correlates included ethnicity (higher exposures among African-American prostate cancer patients vs. white; lower exposures in Hispanic colorectal cancer patients vs. white), and cancer stage (higher exposures in stage IV prostate cancer patients vs. stages 0-II). Education level did not predict patients' DTCA exposure. The implications of these observed inequalities in DTCA exposure on cancer outcomes are discussed. PMID:25357119

A Study of the Frequency and Social Determinants of Exposure to Cancer-Related Direct-to-Consumer Advertising Among Breast, Prostate, and Colorectal Cancer Patients.

PubMed

Tan, Andy S L

2015-01-01

Cancer-related direct-to-consumer advertising (DTCA) is controversial because cancer treatment is complex and entails more risks and costs than typical treatments that are advertised for other conditions. Drawing from the Structural Influence Model of Communication, this study explores communication inequalities in DTCA exposure across social determinants among a population-based sample of 2013 patients diagnosed with breast, prostate, or colorectal cancers. Three survey items assessed patients' frequency of encountering ads concerning treatment alternatives for cancer, dealing with side effects of treatment, and doctors or hospitals offering services for cancer following their diagnosis. The analysis showed that overall exposure to DTCA in this study population was modest (median was once per week). Breast cancer patients reported significantly higher exposure to all three ad categories and overall DTCA exposure than prostate and colorectal cancer patients. Older patients consistently reported lower overall exposure to DTCA across the three cancer types. Other significant correlates included ethnicity (higher exposures among African American prostate cancer patients vs. White; lower exposures in Hispanic colorectal cancer patients vs. White) and cancer stage (higher exposures in Stage IV prostate cancer patients vs. Stages 0-II). Education level did not predict patients' DTCA exposure. The implications of these observed inequalities in DTCA exposure on cancer outcomes are discussed.

Inverse probability of treatment-weighted competing risks analysis: an application on long-term risk of urinary adverse events after prostate cancer treatments.

PubMed

Bolch, Charlotte A; Chu, Haitao; Jarosek, Stephanie; Cole, Stephen R; Elliott, Sean; Virnig, Beth

2017-07-10

To illustrate the 10-year risks of urinary adverse events (UAEs) among men diagnosed with prostate cancer and treated with different types of therapy, accounting for the competing risk of death. Prostate cancer is the second most common malignancy among adult males in the United States. Few studies have reported the long-term post-treatment risk of UAEs and those that have, have not appropriately accounted for competing deaths. This paper conducts an inverse probability of treatment (IPT) weighted competing risks analysis to estimate the effects of different prostate cancer treatments on the risk of UAE, using a matched-cohort of prostate cancer/non-cancer control patients from the Surveillance, Epidemiology and End Results (SEER) Medicare database. Study dataset included men age 66 years or older that are 83% white and had a median follow-up time of 4.14 years. Patients that underwent combination radical prostatectomy and external beam radiotherapy experienced the highest risk of UAE (IPT-weighted competing risks: HR 3.65 with 95% CI (3.28, 4.07); 10-yr. cumulative incidence = 36.5%). Findings suggest that IPT-weighted competing risks analysis provides an accurate estimator of the cumulative incidence of UAE taking into account the competing deaths as well as measured confounding bias.

Barriers and Facilitators of Prostate Cancer Screening among Filipino Men in Hawai’i

PubMed Central

Conde, Francisco A.; Landier, Wendy; Ishida, Dianne; Bell, Rose; Cuaresma, Charlene F.; Misola, Jane

2013-01-01

Purpose/Objectives To examine perceptions, attitudes, and beliefs regarding barriers and facilitators to prostate cancer screening, and to identify potential interventional strategies to promote prostate cancer screening among Filipino men in Hawai’i. Design Exploratory, qualitative. Setting Community-based settings in Hawai’i. Sample 20 Filipino men, 40 years old or older Methods Focus group discussions were tape-recorded, transcribed, and content analysis performed for emergent themes. Main Research Variables Perceptions regarding prostate cancer, barriers and facilitators to prostate cancer screening, and culturally-relevant interventional strategies Findings Perceptions of prostate cancer included fatalism, hopelessness, and dread. Misconceptions regarding causes of prostate cancer, such as frequency of sexual activity, were identified. Barriers to prostate cancer screening included lack of awareness of the need for screening, reticence to seek healthcare when feeling well, fear of cancer diagnosis, financial issues, time constraints, and embarrassment. Presence of urinary symptoms, personal experience with family or friend who had cancer, and receiving recommendations from a healthcare provider regarding screening were facilitators for screening. Potential culturally-relevant interventional strategies to promote prostate cancer screening included screening recommendations from health professionals and cancer survivors; radio/television commercials and newspaper articles targeted to the Filipino community; informational brochures in Tagalog, Ilocano and/or English; and interactive, educational forums facilitated by Filipino multilingual, male healthcare professionals. Conclusions Culturally-relevant interventions are needed that address barriers to prostate cancer screening participation and misconceptions about causes of prostate cancer. Implications for Nursing Findings provide a foundation for future research regarding development of interventional strategies to promote prostate cancer screening among Filipino men. PMID:21356660

Incidental Finding of Cryptococcus on Prostate Biopsy for Prostate Adenocarcinoma Following Cardiac Transplant: Case Report and Review of the Literature.

PubMed

Shah, Sujal I; Bui, Hai; Velasco, Nelson; Rungta, Shilpa

2017-11-06

BACKGROUND Cryptococcus is the third most common invasive fungal organism in immunocompromised patients, including transplant patients, and usually involves the central nervous system and lungs, with a median time to infection of 25 months. We report a case of Cryptococcus of the prostate gland, found as an incidental finding on prostate biopsy for prostate adenocarcinoma, four months following cardiac transplantation. CASE REPORT A 62-year-old male African-American who had a cardiac transplant four months previously, underwent a six-core prostate biopsy for a two-year history of increasing prostate-specific antigen (PSA) levels, and a recent history of non-specific urinary tract symptoms. A prostatic adenocarcinoma, Gleason grade 4+4=8, was diagnosed on histopathology, and 'foamy' cells were seen in the biopsies. Histochemical stains, including Grocott methenamine silver (GMS), and periodic acid-Schiff (PAS) showed abundant round and oval 5-7 µm diameter fungal elements; mucicarmine highlighted the fungal polysaccharide capsule, diagnostic for Cryptococcus. Cryptococcal antigen detection was made by the latex agglutination test and cultures. We reviewed the literature and found 70 published cases (from 1946-2008) of Cryptococcus of the prostate gland, with only one previous case presenting five years following cardiac transplantation. CONCLUSIONS Fungal infections of the prostate are rare, and occur mainly in immunocompromised patients. We present a unique case of prostatic Cryptococcus found incidentally at four months following cardiac transplantation. This case report highlights the need to consider atypical fungal infection as a differential diagnosis for prostatitis in immunosuppressed patients, including transplant patients.

Prostate Cancer Patient Perspectives on the Use of Information in Treatment Decision-Making: A Systematic Review and Qualitative Meta-synthesis

PubMed Central

Kandasamy, Sujane; Khalid, Ahmad Firas; Majid, Umair; Vanstone, Meredith

2017-01-01

Background Men with low- to intermediate-risk prostate cancer are typically asked to choose from a variety of treatment options, including active surveillance, radical prostatectomy, or brachytherapy. The Prolaris cell cycle progression test is intended to provide additional information on personal risk status to assist men with prostate cancer in their choice of treatment. To assist with assessing that new technology, this report synthesizes qualitative research on how men with prostate cancer use information to make decisions about treatment options. Methods We performed a systematic review and qualitative meta-synthesis to retrieve and synthesize findings across primary qualitative studies that report on patient perspectives during prostate cancer treatment decision-making. Results Of 8,610 titles and abstracts reviewed, 29 studies are included in this report. Most men diagnosed with prostate cancer express that their information-seeking pathway extends beyond the medical information received from their health care provider. They access other social resources to attain additional medical information, lived-experience information, and medical administrative information to help support their final treatment decision. Men value privacy, trust, honesty, control, power, organization, and open communication during interactions with their health care providers. They also emphasize the importance of gaining comfort with their treatment choice, having a chance to confirm their health care provider's recommendations (validation of treatment plan), and exercising their preferred level of independence in the treatment decision-making process. Conclusions Although each prostate cancer patient is unique, studies suggest that most patients seek extensive information to help inform their treatment decisions. This may happen before, during, and after the treatment choice is made. Given the amount of information patients may access, it is important that they also establish the trustworthiness of the various types and sources of information. When information conflicts, patients may be unsure about how to proceed. Open collaboration between patients and their health care providers can help patients manage and navigate their concerns so that their values and perspectives are captured in their treatment choices. PMID:28572868

The role of Cajal cells in chronic prostatitis.

PubMed

Haki Yuksel, Ozgur; Urkmez, Ahmet; Verit, Ayhan

2016-07-04

Types of prostatitis can be defined as groups of syndromes in adult men associated with infectious and noninfectious causes characterized frequently by lower abdominal and perineal signs and diverse clinical symptoms and complications. Etiopathogenesis of chronic prostatitis is not well defined. Moreover, its treatment outcomes are not satisfactory. Presence of c-kit positive interstitial cells in human prostate is already known. It has been demonstrated that these cells can be pacemaker cells which trigger spontaneous slow-wave electrical activity in the prostate and can be responsible for the transport of glandular secretion from acinar cells into major and minor prostatic ducts and finally into urethra. In the light of all these data, when presence of a possible inflammatory pathology is thought to involve prostate that secretes and has a reservoir which drains its secretion (for prostate, prostatic urethra), two points are worth mentioning. Impairment of secretion mechanism and collection of secretion within the organ with reflux of the microbial material from its reservoir back into prostate gland. Both of these potential conditions can be explained by ductal neuromuscular mechanism, which induces secretion. We think that in this neuromuscular mechanism interstitial Cajal cells have an important role in chronic prostatitis. Our hypothesis is that curability of prostatitis is correlated with the number of Cajal cells not subjected to apoptosis.

Combination Therapy Improves Survival in Prostate Cancer Model | Center for Cancer Research

Cancer.gov

Surgery and radiotherapy are the recommended treatments for localized prostate cancer. Recurrent prostate cancer, however, is often treated with androgen-deprivation therapy. Most patients who undergo this type of therapy eventually develop castration-resistant prostate cancer (CRPC). Though initially androgen-related therapies for CRPC had been thought to be ineffective, further studies have demonstrated that the disease remains dependent on the signaling of androgens, such as testosterone, for its continued progression. This development suggests that alternative strategies for manipulating androgen signaling may prove useful for treating CRPC.

Identifying New Candidate Genes and Chemicals Related to Prostate Cancer Using a Hybrid Network and Shortest Path Approach

PubMed Central

Wang, Meng; Wu, Kai; Lu, Changhong; Kong, Xiangyin

2015-01-01

Prostate cancer is a type of cancer that occurs in the male prostate, a gland in the male reproductive system. Because prostate cancer cells may spread to other parts of the body and can influence human reproduction, understanding the mechanisms underlying this disease is critical for designing effective treatments. The identification of as many genes and chemicals related to prostate cancer as possible will enhance our understanding of this disease. In this study, we proposed a computational method to identify new candidate genes and chemicals based on currently known genes and chemicals related to prostate cancer by applying a shortest path approach in a hybrid network. The hybrid network was constructed according to information concerning chemical-chemical interactions, chemical-protein interactions, and protein-protein interactions. Many of the obtained genes and chemicals are associated with prostate cancer. PMID:26504486

Cannabinoid Receptors: A Novel Target for Therapy of Prostate Cancer

DTIC Science & Technology

2007-02-01

study could be to develop nonhabit-forming cannabi - noid agonist (s) for the management of prostate cancer . REFERENCES 1. Jemal, A., Siegel, R.W...for Therapy of Prostate Cancer PRINCIPAL INVESTIGATOR: Prof. Hasan Mukhtar, Ph.D (PI) Dr. Farrukh Afaq, Ph.D (Co-Investigator...REPORT DATE: February 2007 TYPE OF REPORT: Annual PREPARED FOR: U.S. Army Medical Research and Materiel Command

[Prostatic calculi: silent stones].

PubMed

Köseoğlu, H; Aslan, G; Sen, B H; Tuna, B; Yörükoğlu, K

2010-06-01

Prostate stones are frequently encountered during transurethral resection of the prostate in urology practice. We aimed to demonstrate the physical and chemical properties of prostate stones. We also aimed to determine possible relationship between inflammation of prostate gland and prostate stones. The consecutive patients (excluding subjects with PSA>or=4ng/ml and urolithiasis), who underwent TURP operation and who were observed to have prostatic calculi during TURP, were included in the study. The prostatic stones obtained from each patient during TURP were analysed for chemical composition and observed under electron microscopy (SEM) for structure and surface morphology. The pathological specimens were assessed by the uropathologist for the final diagnosis and existence and degree of inflammation. Five patients were included in the study. From each patient at least three (range 3-8) samples of stones (diameter varying from 1mm up to 5mm) were obtained. The stones were made of mixed composition of calcium phosphate and calcium carbonate. The stones were found to have lobular surface made up of small spheres under SEM. Histopathological examination of the TURP specimens revealed being prostatic hyperplasia accompanied with inflammation of mild to severe degree. Prostatic stones are concentrically precipitated calcium stones within the prostatic ductuli with granular grape like morphology. Histopathological inflammation seems to be associated with these prostatic calculi.

Prostate Cancer and Bone: The Elective Affinities

PubMed Central

2014-01-01

The onset of metastases dramatically changes the prognosis of prostate cancer patients, determining increased morbidity and a drastic fall in survival expectancy. Bone is a common site of metastases in few types of cancer, and it represents the most frequent metastatic site in prostate cancer. Of note, the prevalence of tumor relapse to the bone appears to be increasing over the years, likely due to a longer overall survival of prostate cancer patients. Bone tropism represents an intriguing challenge for researchers also because the preference of prostate cancer cells for the bone is the result of a sequential series of targetable molecular events. Many factors have been associated with the peculiar ability of prostate cancer cells to migrate in bone marrow and to determine mixed osteoblastic/osteolytic lesions. As anticipated by the success of current targeted therapy aimed to block bone resorption, a better understanding of molecular affinity between prostate cancer and bone microenvironment will permit us to cure bone metastasis and to improve prognosis of prostate cancer patients. PMID:24971315

Conditionally reprogrammed normal and primary tumor prostate epithelial cells: a novel patient-derived cell model for studies of human prostate cancer

PubMed Central

Timofeeva, Olga A.; Palechor-Ceron, Nancy; Li, Guanglei; Yuan, Hang; Krawczyk, Ewa; Zhong, Xiaogang; Liu, Geng; Upadhyay, Geeta; Dakic, Aleksandra; Yu, Songtao; Fang, Shuang; Choudhury, Sujata; Zhang, Xueping; Ju, Andrew; Lee, Myeong-Seon; Dan, Han C.; Ji, Youngmi; Hou, Yong; Zheng, Yun-Ling; Albanese, Chris; Rhim, Johng; Schlegel, Richard; Dritschilo, Anatoly; Liu, Xuefeng

2017-01-01

Our previous study demonstrated that conditional reprogramming (CR) allows the establishment of patient-derived normal and tumor epithelial cell cultures from a variety of tissue types including breast, lung, colon and prostate. Using CR, we have established matched normal and tumor cultures, GUMC-29 and GUMC-30 respectively, from a patient's prostatectomy specimen. These CR cells proliferate indefinitely in vitro and retain stable karyotypes. Most importantly, only tumor-derived CR cells (GUMC-30) produced tumors in xenografted SCID mice, demonstrating maintenance of the critical tumor phenotype. Characterization of cells with DNA fingerprinting demonstrated identical patterns in normal and tumor CR cells as well as in xenografted tumors. By flow cytometry, both normal and tumor CR cells expressed basal, luminal, and stem cell markers, with the majority of the normal and tumor CR cells expressing prostate basal cell markers, CD44 and Trop2, as well as luminal marker, CD13, suggesting a transit-amplifying phenotype. Consistent with this phenotype, real time RT-PCR analyses demonstrated that CR cells predominantly expressed high levels of basal cell markers (KRT5, KRT14 and p63), and low levels of luminal markers. When the CR tumor cells were injected into SCID mice, the expression of luminal markers (AR, NKX3.1) increased significantly, while basal cell markers dramatically decreased. These data suggest that CR cells maintain high levels of proliferation and low levels of differentiation in the presence of feeder cells and ROCK inhibitor, but undergo differentiation once injected into SCID mice. Genomic analyses, including SNP and INDEL, identified genes mutated in tumor cells, including components of apoptosis, cell attachment, and hypoxia pathways. The use of matched patient-derived cells provides a unique in vitro model for studies of early prostate cancer. PMID:28009986

Angiotensin II up-regulates PAX2 oncogene expression and activity in prostate cancer via the angiotensin II type I receptor.

PubMed

Bose, Sudeep K; Gibson, Willietta; Giri, Shailendra; Nath, Narender; Donald, Carlton D

2009-09-01

Paired homeobox 2 gene (PAX2) is a transcriptional regulator, aberrantly expressed in prostate cancer cells and its down-regulation promotes cell death in these cells. The molecular mechanisms of tumor progression by PAX2 over-expression are still unclear. However, it has been reported that angiotensin-II (A-II) induces cell growth in prostate cancer via A-II type 1 receptor (AT1R) and is mediated by the phosphorylation of mitogen activated protein kinase (MAPK) as well as signal transducer and activator of transcription 3 (STAT3). Here we have demonstrated that A-II up-regulates PAX2 expression in prostate epithelial cells and prostate cancer cell lines resulting in increased cell growth. Furthermore, AT1R receptor antagonist losartan was shown to inhibit A-II induced PAX2 expression in prostate cancer. Moreover, analysis using pharmacological inhibitors against MEK1/2, ERK1/2, JAK-II, and phospho-STAT3 demonstrated that AT1R-mediated stimulatory effect of A-II on PAX2 expression was regulated in part by the phosphorylation of ERK1/2, JAK II, and STAT3 pathways. In addition, we have showed that down-regulation of PAX2 by an AT1R antagonist as well as JAK-II and STAT3 inhibitors suppress prostate cancer cell growth. Collectively, these findings show for the first time that the renin-angiotensin system (RAS) may promote prostate tumorigenesis via up-regulation of PAX2 expression. Therefore, PAX2 may be a novel therapeutic target for the treatment of carcinomas such as prostate cancer via the down-regulation of its expression by targeting the AT1R signaling pathways.

Several genes encoding ribosomal proteins are over-expressed in prostate-cancer cell lines: confirmation of L7a and L37 over-expression in prostate-cancer tissue samples.

PubMed

Vaarala, M H; Porvari, K S; Kyllönen, A P; Mustonen, M V; Lukkarinen, O; Vihko, P T

1998-09-25

A cDNA library specific for mRNA over-expressed in prostate cancer was generated by subtractive hybridization of transcripts originating from prostatic hyperplasia and cancer tissues. cDNA encoding ribosomal proteins L4, L5, L7a, L23a, L30, L37, S14 and S18 was found to be present among 100 analyzed clones. Levels of ribosomal mRNA were significantly higher at least in one of the prostate-cancer cell lines, LNCaP, DU-145 and PC-3, than in hyperplastic tissue, as determined by slot-blot hybridization. Furthermore, L23a- and S14-transcript levels were significantly elevated in PC-3 cells as compared with those in the normal prostate epithelial cell line PrEC. Generally, dramatic changes in the mRNA content of the ribosomal proteins were not detected, the most evident over-expression being that of L37 mRNA, which was 3.4 times more abundant in LNCaP cells than in hyperplastic prostate tissue. The over-expression of L7a and L37 mRNA was confirmed in prostate-cancer tissue samples by in situ hybridization. Elevated cancer-related expression of L4 and L30 has not been reported, but levels of the other ribosomal proteins are known to be increased in several types of cancers. These results therefore suggest that prostate cancer is comparable with other types of cancers, in that a larger pool of some ribosomal proteins is gained during the transformation process, by an unknown mechanism.

Transgenerational effects of the endocrine disruptor vinclozolin on the prostate transcriptome and adult onset disease.

PubMed

Anway, Matthew D; Skinner, Michael K

2008-04-01

The ability of an endocrine disruptor exposure during gonadal sex determination to promote a transgenerational prostate disease phenotype was investigated in the current study. Exposure of an F0 gestating female rat to the endocrine disruptor vinclozolin during F1 embryo gonadal sex determination promoted a transgenerational adult onset prostate disease phenotype. The prostate disease phenotype and physiological parameters were determined for males from F1 to F4 generations and the prostate transcriptome was assessed in the F3 generation. Although the prostate in prepubertal animals develops normally, abnormalities involving epithelial cell atrophy, glandular dysgenesis, prostatitis, and hyperplasia of the ventral prostate develop in older animals. The ventral prostate phenotype was transmitted for four generations (F1-F4). Analysis of the ventral prostate transcriptome demonstrated 954 genes had significantly altered expression between control and vinclozolin F3 generation animals. Analysis of isolated ventral prostate epithelial cells identified 259 genes with significantly altered expression between control and vinclozolin F3 generation animals. Characterization of regulated genes demonstrated several cellular pathways were influenced, including calcium and WNT. A number of genes identified have been shown to be associated with prostate disease and cancer, including beta-microseminoprotein (Msp) and tumor necrosis factor receptor superfamily 6 (Fadd). The ability of an endocrine disruptor to promote transgenerational prostate abnormalities appears to involve an epigenetic transgenerational alteration in the prostate transcriptome and male germ-line. Potential epigenetic transgenerational alteration of prostate gene expression by environmental compounds may be important to consider in the etiology of adult onset prostate disease.

Transgenerational Effects of the Endocrine Disruptor Vinclozolin on the Prostate Transcriptome and Adult Onset Disease

PubMed Central

Anway, Matthew D.; Skinner, Michael K.

2018-01-01

PURPOSE The ability of an endocrine disruptor exposure during gonadal sex determination to promote a transgenerational prostate disease phenotype was investigated in the current study. METHODS Exposure of an F0 gestating female rat to the endocrine disruptor vinclozolin during F1 embryo gonadal sex determination promoted a transgenerational adult onset prostate disease phenotype. The prostate disease phenotype and physiological parameters were determined for males from F1 to F4 generations and the prostate transcriptome was assessed in the F3 generation. RESULTS Although the prostate in prepubertal animals develops normally, abnormalities involving epithelial cell atrophy, glandular dysgenesis, prostatitis, and hyperplasia of the ventral prostate develop in older animals. The ventral prostate phenotype was transmitted for four generations (F1–F4). Analysis of the ventral prostate transcriptome demonstrated 954 genes had significantly altered expression between control and vinclozolin F3 generation animals. Analysis of isolated ventral prostate epithelial cells identified 259 genes with significantly altered expression between control and vinclozolin F3 generation animals. Characterization of regulated genes demonstrated several cellular pathways were influenced, including calcium and WNT. A number of genes identified have been shown to be associated with prostate disease and cancer, including beta-microseminoprotein (Msp) and tumor necrosis factor receptor superfamily 6 (Fadd). CONCLUSIONS The ability of an endocrine disruptor to promote transgenerational prostate abnormalities appears to involve an epigenetic transgenerational alteration in the prostate transcriptome and male germ-line. Potential epigenetic transgenerational alteration of prostate gene expression by environmental compounds may be important to consider in the etiology of adult onset prostate disease. PMID:18220299

A large germline deletion in the Chek2 kinase gene is associated with an increased risk of prostate cancer

PubMed Central

Cybulski, C; Wokołorczyk, D; Huzarski, T; Byrski, T; Gronwald, J; Górski, B; Dębniak, T; Masojć, B; Jakubowska, A; Gliniewicz, B; Sikorski, A; Stawicka, M; Godlewski, D; Kwias, Z; Antczak, A; Krajka, K; Lauer, W; Sosnowski, M; Sikorska‐Radek, P; Bar, K; Klijer, R; Zdrojowy, R; Małkiewicz, B; Borkowski, A; Borkowski, T; Szwiec, M; Narod, S A; Lubiński, J

2006-01-01

Background Germline mutations in the Chek2 kinase gene (CHEK2) have been associated with a range of cancer types. Recently, a large deletion of exons 9 and 10 of CHEK2 was identified in several unrelated patients with breast cancer of Czech or Slovak origin. The geographical and ethnic extent of this founder allele has not yet been determined. Participants and methods We assayed for the presence of this deletion, and of three other CHEK2 founder mutations, in 1864 patients with prostate cancer and 5496 controls from Poland. Results The deletion was detected in 24 of 5496 (0.4%) controls from the general population, and is the most common CHEK2 truncating founder allele in Polish patients. The deletion was identified in 15 of 1864 (0.8%) men with unselected prostate cancer (OR 1.9; 95% CI 0.97 to 3.5; p = 0.09) and in 4 of 249 men with familial prostate cancer (OR 3.7; 95% CI 1.3 to 10.8; p = 0.03). These ORs were similar to those associated with the other truncating mutations (IVS2+1G→A, 1100delC). Conclusion A large deletion of exons 9 and 10 of CHEK2 confers an increased risk of prostate cancer in Polish men. The del5395 founder deletion might be present in other Slavic populations, including Ukraine, Belarus, Russia, Baltic and Balkan countries. It will be of interest to see to what extent this deletion is responsible for the burden of prostate cancer in other populations. PMID:17085682

Symptom management strategies for men with early-stage prostate cancer: results from the Prostate Cancer Patient Education Program (PC PEP).

PubMed

Vij, Alok; Kowalkowski, Marc A; Hart, Tae; Goltz, Heather Honoré; Hoffman, David J; Knight, Sara J; Caroll, Peter R; Latini, David M

2013-12-01

While the literature on prostate cancer health-related quality of life has grown extensively, little is known about symptom management strategies used by men to manage treatment-related side effects and the effectiveness of those strategies. We collected 628 symptom management reports from 98 men treated for localized prostate cancer. Participants were recruited from email lists and a prostate cancer clinic in Northern California. Data were collected using the Critical Incident Technique. Symptom management reports were assigned to categories of urinary, sexual, bowel, mental health, systemic, or "other." We calculated descriptive statistics by symptom type and management strategy effectiveness. The most common symptoms were urinary (26 %) and sexual (23 %). Participants' symptom management strategies varied widely, from medical and surgical interventions (20 %) to behavioral strategies (11 %) to diet and lifestyle interventions (12 %). The effectiveness of symptom management strategies varied, with sexual symptoms being managed effectively only 47 % of the time to mental health symptom management strategies considered effective 89 % of the time. Doing nothing was a commonly reported (15 %) response to symptoms and was effective only 14 % of the time. Men report the least effectiveness in symptom management for sexual dysfunction after prostate cancer treatment. Including men's experience with managing treatment side effects may be an important way to improve survivorship programs and make them more acceptable to men. More work is needed to find out why men frequently do nothing in response to symptoms when effective solutions exist and how providers can successfully engage such men.

Symptom Management Strategies for Men with Early-Stage Prostate Cancer: Results from the Prostate Cancer Patient Education Program (PCPEP)

PubMed Central

Vij, Alok; Kowalkowski, Marc A.; Hart, Tae; Goltz, Heather Honoré; Hoffman, David J.; Knight, Sara J.; Caroll, Peter R.

2013-01-01

While the literature on prostate cancer health-related quality of life has grown extensively, little is known about symptom management strategies used by men to manage treatment-related side effects and the effectiveness of those strategies. We collected 628 symptom management reports from 98 men treated for localized prostate cancer. Participants were recruited from email lists and a prostate cancer clinic in Northern California. Data were collected using the Critical Incident Technique. Symptom management reports were assigned to categories of urinary, sexual, bowel, mental health, systemic, or “other.” We calculated descriptive statistics by symptom type and management strategy effectiveness. The most common symptoms were urinary (26 %) and sexual (23 %). Participants’ symptom management strategies varied widely, from medical and surgical interventions (20 %) to behavioral strategies (11 %) to diet and lifestyle interventions (12 %). The effectiveness of symptom management strategies varied, with sexual symptoms being managed effectively only 47 % of the time to mental health symptom management strategies considered effective 89 % of the time. Doing nothing was a commonly reported (15 %) response to symptoms and was effective only 14 % of the time. Men report the least effectiveness in symptom management for sexual dysfunction after prostate cancer treatment. Including men’s experience with managing treatment side effects may be an important way to improve survivorship programs and make them more acceptable to men. More work is needed to find out why men frequently do nothing in response to symptoms when effective solutions exist and how providers can successfully engage such men. PMID:23996206

Prostate Cancer Screening: Should You Get a PSA Test?

MedlinePlus

... Mayo Clinic Staff Cancer screening tests — including the prostate-specific antigen (PSA) test to look for signs of prostate ... of harm to the person undergoing the testing. Prostate-specific antigen (PSA) is a protein produced by both cancerous ( ...

PET imaging of urokinase-type plasminogen activator receptor (uPAR) in prostate cancer: current status and future perspectives.

PubMed

Skovgaard, Dorthe; Persson, Morten; Kjaer, Andreas

2016-01-01

Overexpression of urokinase-type plasminogen activator receptors (uPAR) represents an important biomarker for aggressiveness in most common malignant diseases, including prostate cancer (PC). Accordingly, uPAR expression either assessed directly in malignant PC tissue or assessed directly in plasma (intact/cleaved forms)-provides independent additional clinical information to that contributed by PSA, Gleason score, and other relevant pathological and clinical parameters. In this respect, non-invasive molecular imaging by positron emission tomography (PET) offers a very attractive technology platform, which can provide the required quantitative information on the uPAR expression profile, without the need for invasive procedures and the risk of missing the target due to tumor heterogeneity. These observations support non-invasive PET imaging of uPAR in PC as a clinically relevant diagnostic and prognostic imaging method. In this review, we will focus on the recent development of uPAR PET and the relevance within prostate cancer imaging. Novel antibody and small-molecule radiotracers-targeting uPAR, including a series of uPAR-targeting PET ligands, based on the high affinity peptide ligand AE105, have been synthesized and tested in vitro and in vivo in preclinical murine xenograft models and, recently, in a first-ever clinical uPAR PET study in cancer patients, including patients with PC. In this phase I study, a high and specific uptake of the tracer 64 Cu-DOTA-AE105 was found in both primary tumors and lymph node metastases. The results are encouraging and support large-scale clinical trials to determine the utility of uPAR PET in the management of patients with PC with the goal of improving outcome.

Smooth muscle cell-specific knockout of androgen receptor: a new model for prostatic disease.

PubMed

Welsh, Michelle; Moffat, Lindsey; McNeilly, Alan; Brownstein, David; Saunders, Philippa T K; Sharpe, Richard M; Smith, Lee B

2011-09-01

Androgen-driven stromal-epithelial interactions play a key role in normal prostate development and function as well as in the progression of common prostatic diseases such as benign prostatic hyperplasia and prostate cancer. However, exactly how, and via which cell type, androgens mediate their effects in the adult prostate remains unclear. This study investigated the role for smooth muscle (SM) androgen signaling in normal adult prostate homeostasis and function using mice in which androgen receptor was selectively ablated from prostatic SM cells. In adulthood the knockout (KO) mice displayed a 44% reduction in prostate weight and exhibited histological abnormalities such as hyperplasia, inflammation, fibrosis, and reduced expression of epithelial, SM, and stem cell identify markers (e.g. p63 reduced by 27% and Pten by 31%). These changes emerged beyond puberty and were not explained by changes in serum hormones. Furthermore, in response to exogenous estradiol, adult KO mice displayed an 8.5-fold greater increase in prostate weight than controls and developed urinary retention. KO mice also demonstrated a reduced response to castration compared with controls. Together these results demonstrate that prostate SM cells are vital in mediating androgen-driven stromal-epithelial interactions in adult mouse prostates, determining cell identity and function and limiting hormone-dependent epithelial cell proliferation. This novel mouse model provides new insight into the possible role for SM androgen action in prostate disease.

Tetracycline treatment of type III prostatitis nanobacteria infection of 100 cases report

NASA Astrophysics Data System (ADS)

Guo, Junyi; Li, Chongxian; Wu, Baisuo; Hao, Shaojun; Ming, Aimin; Zhang, Xinji; Li, Wenjun; Zhang, Zhengchen

2018-04-01

To investigate the efficacy of tetracycline treatment of nanobacterial infection in 100 cases of type III prostatitis. randomly divided into treatment group and control group with double blind method, the treatment group was given Tetracycline Tablets 250mg, oral, 2 times a day; the control group were treated with Levofloxacin Tablets 0.lg, oral, 2 times a day; observation of curative effect of two groups of patients after 1 months of treatment. after the treatment group patients NIH-CPSI score and pain, urinary symptoms and quality of life scores were significantly lower than that of control group (P<0.01); after treatment, observation group lecithin corpuscle scale score was significantly higher than the control group (P<0.05). The treatment group and the control group patients after prostate fluid and cultured positive cases of nanobacterial numbers were 21 (21%) and 100 cases (100%), the positive rate of nanobacteria in observation group was significantly lower than the control group (P<0.05). There is a good effect Tetracycline Tablets treatment of nanobacterial infection of type III prostatitis.

GPRC6A regulates prostate cancer progression

PubMed Central

Pi, Min; Quarles, L. Darryl

2011-01-01

BACKGROUND GPRC6A is a nutrient sensing GPCR that is activated in vitro by a variety of ligands, including amino acids, calcium, zinc, osteocalcin (OC) and testosterone. The association between nutritional factors and risk of prostate cancer, the finding of increased expression of OC in prostate cancer cells and the association between GPRC6A and risk of prostate cancer in Japanese men implicates a role of GPRC6A in prostate cancer. METHODS We examined if GPRC6A is expressed in human prostate cancer cell lines and used siRNA-mediated knockdown GPRC6A expression in prostate cancer cells to explore the function of GPRC6A in vitro. To assess the role GPRC6A in prostate cancer progression in vivo we intercrossed Gprc6a−/− mice onto the TRAMP mouse prostate cancer model. RESULTS GPRC6A transcripts were markedly increased in prostate cancer cell lines 22Rv1, PC-3 and LNCaP, compared to the normal prostate RWPE-1 cell line. In addition, a panel of GPRC6A ligands, including calcium, OC, and arginine, exhibited in prostate cancer cell lines a dose-dependent stimulation of ERK activity, cell proliferation, chemotaxis, and prostate specific antigen and Runx 2 gene expression. These responses were inhibited by siRNA-mediated knockdown of GPRC6A. Finally, transfer of Gprc6a deficiency onto a TRAMP mouse model of prostate cancer significantly retarded prostate cancer progression and improved survival of compound Gprc6a−/−/TRAMP mice. CONCLUSIONS GPRC6A is a novel molecular target for regulating prostate growth and cancer progression. Increments in GPRC6A may augment the ability of prostate cancer cells to proliferate in response to dietary and bone derived ligands. PMID:21681779

Screening for Prostate Cancer: US Preventive Services Task Force Recommendation Statement.

PubMed

Grossman, David C; Curry, Susan J; Owens, Douglas K; Bibbins-Domingo, Kirsten; Caughey, Aaron B; Davidson, Karina W; Doubeni, Chyke A; Ebell, Mark; Epling, John W; Kemper, Alex R; Krist, Alex H; Kubik, Martha; Landefeld, C Seth; Mangione, Carol M; Silverstein, Michael; Simon, Melissa A; Siu, Albert L; Tseng, Chien-Wen

2018-05-08

In the United States, the lifetime risk of being diagnosed with prostate cancer is approximately 13%, and the lifetime risk of dying of prostate cancer is 2.5%. The median age of death from prostate cancer is 80 years. Many men with prostate cancer never experience symptoms and, without screening, would never know they have the disease. African American men and men with a family history of prostate cancer have an increased risk of prostate cancer compared with other men. To update the 2012 US Preventive Services Task Force (USPSTF) recommendation on prostate-specific antigen (PSA)-based screening for prostate cancer. The USPSTF reviewed the evidence on the benefits and harms of PSA-based screening for prostate cancer and subsequent treatment of screen-detected prostate cancer. The USPSTF also commissioned a review of existing decision analysis models and the overdiagnosis rate of PSA-based screening. The reviews also examined the benefits and harms of PSA-based screening in patient subpopulations at higher risk of prostate cancer, including older men, African American men, and men with a family history of prostate cancer. Adequate evidence from randomized clinical trials shows that PSA-based screening programs in men aged 55 to 69 years may prevent approximately 1.3 deaths from prostate cancer over approximately 13 years per 1000 men screened. Screening programs may also prevent approximately 3 cases of metastatic prostate cancer per 1000 men screened. Potential harms of screening include frequent false-positive results and psychological harms. Harms of prostate cancer treatment include erectile dysfunction, urinary incontinence, and bowel symptoms. About 1 in 5 men who undergo radical prostatectomy develop long-term urinary incontinence, and 2 in 3 men will experience long-term erectile dysfunction. Adequate evidence shows that the harms of screening in men older than 70 years are at least moderate and greater than in younger men because of increased risk of false-positive results, diagnostic harms from biopsies, and harms from treatment. The USPSTF concludes with moderate certainty that the net benefit of PSA-based screening for prostate cancer in men aged 55 to 69 years is small for some men. How each man weighs specific benefits and harms will determine whether the overall net benefit is small. The USPSTF concludes with moderate certainty that the potential benefits of PSA-based screening for prostate cancer in men 70 years and older do not outweigh the expected harms. For men aged 55 to 69 years, the decision to undergo periodic PSA-based screening for prostate cancer should be an individual one and should include discussion of the potential benefits and harms of screening with their clinician. Screening offers a small potential benefit of reducing the chance of death from prostate cancer in some men. However, many men will experience potential harms of screening, including false-positive results that require additional testing and possible prostate biopsy; overdiagnosis and overtreatment; and treatment complications, such as incontinence and erectile dysfunction. In determining whether this service is appropriate in individual cases, patients and clinicians should consider the balance of benefits and harms on the basis of family history, race/ethnicity, comorbid medical conditions, patient values about the benefits and harms of screening and treatment-specific outcomes, and other health needs. Clinicians should not screen men who do not express a preference for screening. (C recommendation) The USPSTF recommends against PSA-based screening for prostate cancer in men 70 years and older. (D recommendation).

Brachyury Essential for Notochord Cell Fate, Not Proliferation or EMT | Center for Cancer Research

Cancer.gov

The Brachyury or T gene encodes a transcription factor that is essential for body axis elongation during embryonic development. T is also highly expressed in chordomas, rare sarcomas derived from notochord cells, and a number of additional tumor types, including lung, prostate, and colon cancers. 

Prostate Brachytherapy With Oblique Needles to Treat Large Glands and Overcome Pubic Arch Interference

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ryu, Bon; Imaging Research Laboratories, Robarts Research Institute, University of Western Ontario, London, Ontario; Bax, Jeff

2012-08-01

Purpose: First, to show that low-dose-rate prostate brachytherapy plans using oblique needle trajectories are more successful than parallel trajectories for large prostates with pubic arch interference (PAI); second, to test the accuracy of delivering an oblique plan by using a three-dimensional (3D) transrectal ultrasonography (TRUS)-guided mechatronic system. Methods and Materials: Prostates were contoured for 5 subjects' 3D TRUS images showing a maximum PAI of {<=}1 cm and a prostate volume of <50 cc. Two planning studies were done. First, prostate contours were artificially enlarged to 45 to 80 cc in 5- to 10-cc increments for a single subject. Second, allmore » subject prostate contours were enlarged to 60 cc. For each study, three types of plans were manually created for comparison: a parallel needle template (PT) plan, a parallel needle no-template (PNT) plan, and an oblique needle no-template (OBL) plan. Needle positions and angles were not discretized for nontemplate plans. European Society for Therapeutic Radiology and Oncology dose-volume histogram guidelines, iodine-125 (145-Gy prescription, 0.43 U), and needle angles of <15 Degree-Sign were used. An OBL plan was delivered to a pubic arch containing a 60-cc prostate phantom that mimicked the anatomy of the subject with the greatest PAI (23% by volume). Results: In the increasing-prostate volume study, OBL plans were successful for prostates of {<=}80 cc, and PT plans were successful for prostates of <65 cc. In paired, one-sided t tests for the 60-cc volume study, OBL plans showed dosimetric improvements for all organs compared to both of the parallel type plans (p < 0.05); PNT plans showed a benefit only in planning target volumes receiving more than 100 Gy compared to PT plans. A computed tomography scan of the phantom showed submillimeter seed placement accuracy in all directions. Conclusion: OBL plans were significantly better than parallel plans, and an OBL plan was accurately delivered to a 60-cc prostate phantom with 23% PAI by volume.« less

[Animal models of autoimmune prostatitis and their evaluation criteria].

PubMed

Shen, Jia-ming; Lu, Jin-chun; Yao, Bing

2016-03-01

Chronic prostatitis is a highly prevalent disease of unclear etiology. Researches show that autoimmune reaction is one cause of the problem. An effective animal model may help a lot to understand the pathogenesis and find proper diagnostic and therapeutic strategies of the disease. Currently used autoimmune prostatitis-related animal models include those of age-dependent spontaneous prostatitis, autoimmune regulator-dependent spontaneous prostatitis, self antigen-induced prostatitis, and steroid-induced prostatitis. Whether an animal model of autoimmune prostatitis is successfully established can be evaluated mainly from the five aspects: histology, morphology, specific antigens, inflammatory factors, and pain intensity.

Carcinogenic effects of cadmium in the noble (NBL/Cr) rat: induction of pituitary, testicular, and injection site tumors and intraepithelial proliferative lesions of the dorsolateral prostate.

PubMed

Waalkes, M P; Anver, M; Diwan, B A

1999-12-01

Cadmium is a known human carcinogen based on findings of lung cancer in exposed populations. A more controversial target site for cadmium is the human prostate gland, for which some studies indicate a link between cadmium exposure and cancer. Our work in various strains of Wistar rats has shown that cadmium can induce tumors in the ventral lobe of the prostate. The relevance of this type of lesion to human prostate cancer has been questioned because the ventral lobe of the rat prostate, unlike the dorsolateral lobe, has no embryological homolog in the human gland. In this study we investigated the chronic toxic and carcinogenic effects of cadmium in the Noble (NBL/Cr) rat, with particular attention to lesions of the prostate. Cadmium chloride (CdCl2) was given as a single sc injection (0, 1, 2, 4, 8, 16, or 32 micromol/kg) to groups (initially n = 30) of 10-week-old rats. Rats were observed for up to 72 weeks following exposure. In rats that were injected with the lower doses of cadmium (< or =4 micromol/kg), a clear dose-related increase in proliferative lesions of the dorsolateral prostate occurred (0 micromol/kg = 36% incidence, 1 micromol/kg = 62%, 2 micromol/kg = 65%; 4 micromol/kg = 79%; trend p < 0.003). Lesions were described as intraepithelial hyperplasia with occasional areas of atypical epithelial cells, without stromal invasion. At higher doses (> or =8 micromol/kg) the proliferative-lesion response in the dorsolateral prostate gradually declined to near control levels (8 micromol/kg = 63%; 16 micromol/kg = 60%; 32 micromol/kg = 52%). The loss of prostatic response at the higher doses of cadmium was probably due to loss of testicular function secondary to cadmium treatment. This was reflected in a very high incidence (>90%) of lesions, indicative of testicular hypofunction, including tubular degeneration, mineralization, and interstitial (Leydig) cell tumors, at doses in excess of 16 micromol/kg. Malignant injection-site sarcomas occurred at the two highest doses of cadmium, while pituitary adenomas were elevated by cadmium exposure at the highest dose. These results show that cadmium induces proliferative lesions in the dorsolateral prostate of the Noble rat, a model having a presumed relevance to human prostate cancers.

Genetic variation in IL-16 miRNA target site and time to prostate cancer diagnosis in African American men

PubMed Central

Hughes, Lucinda; Ruth, Karen; Rebbeck, Timothy R.; Giri, Veda N.

2013-01-01

Background Men with a family history of prostate cancer and African American men are at high risk for prostate cancer and in need of personalized risk estimates to inform screening decisions. This study evaluated genetic variants in genes encoding microRNA (miRNA) binding sites for informing of time to prostate cancer diagnosis among ethnically-diverse, high-risk men undergoing prostate cancer screening. Methods The Prostate Cancer Risk Assessment Program (PRAP) is a longitudinal screening program for high-risk men. Eligibility includes men ages 35-69 with a family history of prostate cancer or African descent. Participants with ≥ 1 follow-up visit were included in the analyses (n=477). Genetic variants in regions encoding miRNA binding sites in four target genes (ALOX15, IL-16, IL-18, and RAF1) previously implicated in prostate cancer development were evaluated. Genotyping methods included Taqman® SNP Genotyping Assay (Applied Biosystems) or pyrosequencing. Cox models were used to assess time to prostate cancer diagnosis by risk genotype. Results Among 256 African Americans with ≥ one follow-up visit, the TT genotype at rs1131445 in IL-16 was significantly associated with earlier time to prostate cancer diagnosis vs. the CC/CT genotypes (p=0.013), with a suggestive association after correction for false-discovery (p=0.065). Hazard ratio after controlling for age and PSA for TT vs. CC/CT among African Americans was 3.0 (95% CI 1.26-7.12). No association to time to diagnosis was detected among Caucasians by IL-16 genotype. No association to time to prostate cancer diagnosis was found for the other miRNA target genotypes. Conclusions Genetic variation in IL-16 encoding miRNA target site may be informative of time to prostate cancer diagnosis among African American men enrolled in prostate cancer risk assessment, which may inform individualized prostate cancer screening strategies in the future. PMID:24061634

Monoamine Oxidase Deficiency Causes Prostate Atrophy and Reduces Prostate Progenitor Cell Activity.

PubMed

Yin, Lijuan; Li, Jingjing; Liao, Chun-Peng; Jason Wu, Boyang

2018-04-10

Monoamine oxidases (MAOs) degrade a number of biogenic and dietary amines, including monoamine neurotransmitters, and play an essential role in many biological processes. Neurotransmitters and related neural events have been shown to participate in the development, differentiation, and maintenance of diverse tissues and organs by regulating the specialized cellular function and morphological structures of innervated organs such as the prostate. Here we show that mice lacking both MAO isoforms, MAOA and MAOB, exhibit smaller prostate mass and develop epithelial atrophy in the ventral and dorsolateral prostates. The cellular composition of prostate epithelium showed reduced CK5 + or p63 + basal cells, accompanied by lower Sca-1 expression in p63 + basal cells, but intact differentiated CK8 + luminal cells in MAOA/B-deficient mouse prostates. MAOA/B ablation also decreased epithelial cell proliferation without affecting cell apoptosis in mouse prostates. Using a human prostate epithelial cell line, we found that stable knockdown of MAOA and MAOB impaired the capacity of prostate stem cells to form spheres, coinciding with a reduced CD133 + /CD44 + /CD24 - stem cell population and less expression of CK5 and select stem cell markers, including ALDH1A1, TROP2, and CD166. Alternative pharmacological inhibition of MAOs also repressed prostate cell stemness. In addition, we found elevated expression of MAOA and MAOB in epithelial and/or stromal components of human prostate hyperplasia samples compared with normal prostate tissues. Taken together, our findings reveal critical roles for MAOs in the regulation of prostate basal progenitor cells and prostate maintenance. Stem Cells 2018. © AlphaMed Press 2018.

LIGHT-ing Up Prostate Cancer for Immunotherapy

DTIC Science & Technology

2016-10-01

Award Number: W81XWH-15-1-0491 TITLE: LIGHT -ing up prostate cancer for immunotherapy PRINCIPAL INVESTIGATOR: W. Martin Kast, Ph.D...FORM TO THE ABOVE ADDRESS. 1. REPORT DATE October 2016 2. REPORT TYPE Annual 3. DATES COVERED 4. TITLE AND SUBTITLE LIGHT -ing up prostate cancer...expression of LIGHT molecules within the tumor milieu counteracts cancer immune-evasion mechanisms and instigates activation and migration of T-cells

Developing an Instrument to Measure Socioeconomic Disparities in Quality of Care for Men with Early-Stage Prostate Cancer

DTIC Science & Technology

2011-09-01

Cystorrhaphy, suture of bladder wound), 52332 (Insertion of ureteral stent ) Diagnosis of urinary incontinence: ICD-9: 599.82 (Intrinsic...first outcome measure we will investigate will be urinary side effects of prostate cancer treatment. Because urinary continence and urinary side...initial findings have been quite striking. Most patients who undergo treatment for prostate cancer are diagnosed with some type of urinary

How MMPs Impact Bone Responses to Metastatic Prostate Cancer

DTIC Science & Technology

2009-02-01

STATEMENT Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Using an animal model of prostate tumor...prostate tumor progression in the bone since no difference in osteolytic or osteoblastic responses between wild type and MMP-9 deficient animals were...described as the ‘vicious cycle’ (4). Using an animal model of 4 tumor progression in the bone, we have previously identified a group of enzymes known as

Isolation and Characterization of Prostate Cancer Stem Cells

DTIC Science & Technology

2009-08-01

The Prostate Manuscript ID: PROS-09-224.R1 Wiley - Manuscript type: Original Article Date Submitted by the Author: 18-Sep-2009 Complete List of ...subpopulation of basal cells has stem cell characteristics raises some interesting questions about the cell of origin for prostate cancer. Can both basal...positively for AMACR and the retention of 7 a p63+ basal layer, the basal-derived lesions fulfill the histologic criteria used

Prostate Cancer Research Training Program

DTIC Science & Technology

2017-09-01

Award Number: W81XWH-16-1-0549 TITLE: Prostate Cancer Research Training Program PRINCIPAL INVESTIGATOR: David M. Lubaroff, PhD CONTRACTING...ORGANIZATION: University of Iowa Iowa City, IA 52242 REPORT DATE: September 2017 TYPE OF REPORT: Annual PREPARED FOR: U.S. Army Medical Research ...Prostate Cancer Research Training Program 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-16-1-0549 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S

Prostate Cancer Genetics in African Americans

DTIC Science & Technology

2014-09-01

ADDRESS. 1. REPORT DATE 2 . REPORT TYPE Annual 3. DATES COVERED 15 Aug 2013 – 14 Aug 2014 4. TITLE AND SUBTITLE Prostate Cancer Genetics in...first two years of this grant has involved (1) hiring and training of culturally competent research personnel; ( 2 ) the establishment of a project...was no indication of familial prostate cancer. Task 2 : Data Collection and Management (Years 1- 3) The study-specific database has been

New players for advanced prostate cancer and the rationalisation of insulin-sensitising medication.

PubMed

Gunter, Jennifer H; Sarkar, Phoebe L; Lubik, Amy A; Nelson, Colleen C

2013-01-01

Obesity and type 2 diabetes are recognised risk factors for the development of some cancers and, increasingly, predict more aggressive disease, treatment failure, and cancer-specific mortality. Many factors may contribute to this clinical observation. Hyperinsulinaemia, dyslipidaemia, hypoxia, ER stress, and inflammation associated with expanded adipose tissue are thought to be among the main culprits driving malignant growth and cancer advancement. This observation has led to the proposal of the potential utility of "old players" for the treatment of type 2 diabetes and metabolic syndrome as new cancer adjuvant therapeutics. Androgen-regulated pathways drive proliferation, differentiation, and survival of benign and malignant prostate tissue. Androgen deprivation therapy (ADT) exploits this dependence to systemically treat advanced prostate cancer resulting in anticancer response and improvement of cancer symptoms. However, the initial therapeutic response from ADT eventually progresses to castrate resistant prostate cancer (CRPC) which is currently incurable. ADT rapidly induces hyperinsulinaemia which is associated with more rapid treatment failure. We discuss current observations of cancer in the context of obesity, diabetes, and insulin-lowering medication. We provide an update on current treatments for advanced prostate cancer and discuss whether metabolic dysfunction, developed during ADT, provides a unique therapeutic window for rapid translation of insulin-sensitising medication as combination therapy with antiandrogen targeting agents for the management of advanced prostate cancer.

Suppressed prostate epithelial development with impaired branching morphogenesis in mice lacking stromal fibromuscular androgen receptor.

PubMed

Lai, Kuo-Pao; Yamashita, Shinichi; Vitkus, Spencer; Shyr, Chih-Rong; Yeh, Shuyuan; Chang, Chawnshang

2012-01-01

Using the cre-loxP system, we generated a new mouse model [double stromal androgen receptor knockout (dARKO)] with selectively deleted androgen receptor (AR) in both stromal fibroblasts and smooth muscle cells, and found the size of the anterior prostate (AP) lobes was significantly reduced as compared with those from wild-type littermate controls. The reduction in prostate size of the dARKO mouse was accompanied by impaired branching morphogenesis and partial loss of the infolding glandular structure. Further dissection found decreased proliferation and increased apoptosis of the prostate epithelium in the dARKO mouse AP. These phenotype changes were further confirmed with newly established immortalized prostate stromal cells (PrSC) from wild-type and dARKO mice. Mechanistically, IGF-1, placental growth factor, and secreted phosphoprotein-1 controlled by stromal AR were differentially expressed in PrSC-wt and PrSC-ARKO. Moreover, the conditioned media (CM) from PrSC-wt promoted prostate epithelium growth significantly as compared with CM from PrSC-dARKO. Finally, adding IGF-1/placental growth factor recombinant proteins into PrSC-dARKO CM was able to partially rescue epithelium growth. Together, our data concluded that stromal fibromuscular AR could modulate epithelium growth and maintain cellular homeostasis through identified growth factors.

Prostate Cancer Prevention (PDQ®)—Patient Version

Cancer.gov

Prostate cancer prevention approaches include avoiding risk factors when possible, increasing protective factors, and chemoprevention. Learn more about prostate cancer prevention in this expert-reviewed summary.

Development of New Treatments for Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

DiPaola, R. S.; Abate-Shen, C.; Hait, W. N.

2005-02-01

The Dean and Betty Gallo Prostate Cancer Center (GPCC) was established with the goal of eradicating prostate cancer and improving the lives of men at risk for the disease through research, treatment, education and prevention. GPCC was founded in the memory of Dean Gallo, a beloved New Jersey Congressman who died tragically of prostate cancer diagnosed at an advanced stage. GPCC unites a team of outstanding researchers and clinicians who are committed to high-quality basic research, translation of innovative research to the clinic, exceptional patient care, and improving public education and awareness of prostate cancer. GPCC is a center ofmore » excellence of The Cancer Institute of New Jersey, which is the only NCI-designated comprehensive cancer center in the state. GPCC efforts are now integrated well as part of our Prostate Program at CINJ, in which Dr. Robert DiPaola and Dr. Cory Abate-Shen are co-leaders. The Prostate Program unites 19 investigators from 10 academic departments who have broad and complementary expertise in prostate cancer research. The overall goal and unifying theme is to elucidate basic mechanisms of prostate growth and oncogenesis, with the ultimate goal of promoting new and effective strategies for the eradication of prostate cancer. Members' wide range of research interests collectively optimize the chances of providing new insights into normal prostate biology and unraveling the molecular pathophysiology of prostate cancer. Cell culture and powerful animal models developed by program members recapitulate the various stages of prostate cancer progression, including prostatic intraepithelial neoplasia, adenocarcinoma, androgen-independence, invasion and metastases. These models promise to further strengthen an already robust program of investigator-initiated therapeutic clinical trials, including studies adopted by national cooperative groups. Efforts to translate laboratory results into clinical studies of early detection and chemoprevention are underway. The specific goals of this program are: (1) To investigate the molecular mechanisms underlying normal prostate growth and differentiation and elucidate the molecular mechanisms underlying prostate oncogenesis. (2) To build on fundamental knowledge to develop effective therapeutic approaches for the treatment of prostate cancer. (3) To improve the control of prostate cancer through early detection, chemoprevention, and outreach and education. This new disease-based program is structured to improve interdisciplinary interactions and translational results. Already, through the dynamic leadership of Drs. Cory Abate-Shen and Robert DiPaola, new investigators were attracted to the field, new collaborations engendered, and numerous investigator-initiated trials implemented. Progress in GPCC and the program overall has been outstanding. The Center has success in uniting investigators with broad and complementary expertise in prostate cancer research. The overall goal and unifying theme is to elucidate basic mechanisms of prostate growth and oncogenesis, with the ultimate goal of promoting new and effective strategies for the eradication of prostate cancer in patients and populations at risk. Members wide range of research interests collectively optimize the chances of providing new insights into normal prostate biology and unraveling the molecular pathophysiology of prostate cancer. Studies in cell culture and powerful animal models developed recapitulate the various stages of prostate cancer progression, including prostatic intraepithelial neoplasia, adenocarcinoma, androgen-independence, invasion and metastases. These models promise to further strengthen an already robust program of investigator-initiated therapeutic clinical trials, including studies adopted by national cooperative groups. Efforts to translate laboratory results into clinical studies of early detection and chemoprevention are underway.« less

The effectiveness of inking needle core prostate biopsies for preventing patient specimen identification errors: a technique to address Joint Commission patient safety goals in specialty laboratories.

PubMed

Raff, Lester J; Engel, George; Beck, Kenneth R; O'Brien, Andrea S; Bauer, Meagan E

2009-02-01

The elimination or reduction of medical errors has been a main focus of health care enterprises in the United States since the year 2000. Elimination of errors in patient and specimen identification is a key component of this focus and is the number one goal in the Joint Commission's 2008 National Patient Safety Goals Laboratory Services Program. To evaluate the effectiveness of using permanent inks to maintain specimen identity in sequentially submitted prostate needle biopsies. For a 12-month period, a grossing technician stained each prostate core with permanent ink developed for inking of pathology specimens. A different color was used for each patient, with all the prostate cores from all vials for a particular patient inked with the same color. Five colors were used sequentially: green, blue, yellow, orange, and black. The ink was diluted with distilled water to a consistency that allowed application of a thin, uniform coating of ink along the edges of the prostate core. The time required to ink patient specimens comprising different numbers of vials and prostate biopsies was timed. The number and type of inked specimen discrepancies were evaluated. The identified discrepancy rate for prostate biopsy patients was 0.13%. The discrepancy rate in terms of total number of prostate blocks was 0.014%. Diluted inks adhered to biopsy contours throughout tissue processing. The tissue showed no untoward reactions to the inks. Inking did not affect staining (histochemical or immunohistochemical) or pathologic evaluation. On average, inking prostate needle biopsies increases grossing time by 20%. Inking of all prostate core biopsies with colored inks, in sequential order, is an aid in maintaining specimen identity. It is a simple and effective method of addressing Joint Commission patient safety goals by maintaining specimen identity during processing of similar types of gross specimens. This technique may be applicable in other specialty laboratories and high-volume laboratories, where many similar tissue specimens are processed.

Leveraging the Family Influence of Women in Prostate Cancer Efforts Targeting African American Men.

PubMed

Okoro, O N; Rutherford, C A; Witherspoon, S F

2017-08-25

Incidence rate of prostate cancer among African American (AA) men is 1.6 times that in White men. Prevention efforts in this population have typically been through faith-based organizations and barber shops, with a few including significant others. Culturally, women are known to have a strong influence in the AA family. The current study assessed prostate cancer knowledge and explored perceptions on the roles of women in prostate cancer prevention. To assess prostate cancer knowledge, a 25-item questionnaire was administered to convenience samples of AA women (n = 297) and men (n = 199). Four focus groups were conducted to explore perceptions on the role of women in prostate cancer prevention. Men had a higher mean score (13.2; max of 25) than women (11.4) for knowledge of prostate cancer. For the men, higher knowledge scores were associated with having a family member diagnosed with prostate cancer and likelihood to engage healthcare providers about prostate cancer (p < 0.05). Themes from the focus groups included education/information resource, support and encouragement, instituting a "culture" of regular primary care, modeling healthcare-seeking behavior, surveillance and monitoring, motivation, and influencing diet. The major barrier to women engaging in the roles identified was limited knowledge. Including women in educational interventions may yield added benefits particularly in encouraging AA men to seek regular primary care. This affords men opportunities for dialog with healthcare providers about prostate cancer and informed decision making regarding screening.

Profiling of zinc altered gene expression in human prostate normal versus cancer cells: a time course study

PubMed Central

Lin, Shu-fei; Wei, Hua; Maeder, Dennis; Franklin, Renty B.; Feng, Pei

2010-01-01

We have demonstrated that zinc exposure induces apoptosis in human prostate cancer cells (PC-3) and benign hyperplasia cells (BPH), but not in normal prostate cells (HPR-1). However, the mechanisms underlying the effects of zinc on prostate cancer cell growth and zinc homeostasis remain unclear. To explore the zinc effect on gene expression profiles in normal (HPR-1) and malignant prostate cells (PC-3), we conducted a time course study of Zn treatment with microarray analysis. Microarray data were evaluated and profiled using computational approach for the primary and secondary data analyses. Final analyses were focused on the genes: 1. highly sensitive to zinc, 2. associated with zinc homeostasis, i.e. metallothioneins (MTs), solute zinc carriers (ZIPs) and zinc exporters (ZnTs), 3. relevant to several oncogenic pathways. Zinc-mediated mRNA levels of MT isotypes were further validated by semi-quantitative RT-PCR. Results showed that zinc effect on genome-wide expression patterns was cell type specific, and zinc appeared to have mainly down-regulatory effects on thousands of genes (1,953 in HPR-1; 3,534 in PC-3) with a threshold of ±2.5-fold, while fewer genes were up-regulated (872 in HPR-1; 571 in PC-3). The patterns of zinc effect on functional MT genes’ expression provided evidence for the cell-type dependent zinc accumulation and zinc-induced apoptosis in prostate cells. In PC-3 cells, zinc significantly up-regulated the expression of MT-1 isotypes -J and -M, denoted previously as “non-functional” MT genes, and now a depictive molecular structure of MT-1J was proposed. Examination of genes involved in oncogenic pathways indicated that certain genes, e.g. Fos, Akt1, Jak3 and PI3K were highly regulated by zinc with cell type specificity. This work provided an extensive database on zinc related prostate cancer research. The strategy of data analysis was devoted to find genes highly sensitive to Zn, and the genes associated with zinc accumulation and zinc-induced apoptosis. The results indicate that zinc regulation of gene expression is cell-type specific, and MT genes play important roles in prostate malignancy. PMID:19071009

Beyond immune checkpoint blockade: new approaches to targeting host-tumor interactions in prostate cancer: report from the 2014 Coffey-Holden prostate cancer academy meeting.

PubMed

Miyahira, Andrea K; Kissick, Haydn T; Bishop, Jennifer L; Takeda, David Y; Barbieri, Christopher E; Simons, Jonathan W; Pienta, Kenneth J; Soule, Howard R

2015-03-01

The 2014 Coffey-Holden Prostate Cancer Academy Meeting, held in La Jolla, CA from June 26 to 29, 2014, was themed: "Beyond Immune Checkpoint Blockade: New Approaches to Targeting Host-Tumor Interactions in Prostate Cancer." Sponsored by the Prostate Cancer Foundation (PCF), this annual, invitation-only meeting is structured as an action-tank, and brought together 72 investigators with diverse academic backgrounds to discuss the most relevant topics in the fields of prostate cancer immunotherapy and the tumor microenvironment. The questions addressed at the meeting included: mechanisms underlying the successes and failures of prostate cancer immunotherapies, how to trigger an effective immune response against prostate cancer, the tumor microenvironment and its role in therapy resistance and tumor metastasis, clinically relevant prostate cancer mouse models, how host-tumor interactions affect current therapies and tumor phenotypes, application of principles of precision medicine to prostate cancer immunotherapy, optimizing immunotherapy clinical trial design, and complex multi-system interactions that affect prostate cancer and immune responses including the effects of obesity and the potential role of the host microbiome. This article highlights the most significant recent progress and unmet needs that were discussed at the meeting toward the goal of speeding the development of optimal immunotherapies for the treatment of prostate cancer. © 2014 Wiley Periodicals, Inc.

Serum ferritin in combination with prostate-specific antigen improves predictive accuracy for prostate cancer.

PubMed

Wang, Xijuan; An, Peng; Zeng, Jiling; Liu, Xiaoyan; Wang, Bo; Fang, Xuexian; Wang, Fudi; Ren, Guoping; Min, Junxia

2017-03-14

Ferritin is highly expressed in many cancer types. Although a few studies have reported an association between high serum ferritin levels and an increased risk of prostate cancer, the results are inconsistent. Therefore, we performed a large case-control study consisting of 2002 prostate cancer patients and 951 control patients with benign prostatic hyperplasia (BPH). We found that high ferritin levels were positively associated with increased serum prostate-specific antigen (PSA) levels and prostate cancer risk; each 100 ng/ml increase in serum ferritin increased the odds ratio (OR) by 1.20 (95% CI: 1.13-1.36). In the prostate cancer group, increased serum ferritin levels were significantly correlated with higher Gleason scores (p < 0.001). Notably, serum PSA values had even higher predictive accuracy among prostate cancer patients with serum ferritin levels > 400 ng/ml (Gleason score + total PSA correlation: r = 0.38; Gleason score + free PSA correlation: r = 0.49). Moreover, using immunohistochemistry, we found that prostate tissue ferritin levels were significantly higher (p < 0.001) in prostate cancer patients (n = 129) compared to BPH controls (n = 31). Prostate tissue ferritin levels were also highly correlated with serum ferritin when patients were classified by cancer severity (r = 0.81). Importantly, we found no correlation between serum ferritin levels and the inflammation marker C-reactive protein (CRP) in prostate cancer patients. In conclusion, serum ferritin is significantly associated with prostate cancer and may serve as a non-invasive biomarker to complement the PSA test in the diagnosis and prognostic evaluation of prostate cancer.

[Epigenetics of prostate cancer].

PubMed

Yi, Xiao-Ming; Zhou, Wen-Quan

2010-07-01

Prostate cancer is one of the most common malignant tumors in males, and its etiology and pathogenesis remain unclear. Epigenesis is involved in prostate cancer at all stages of the process, and closely related with its growth and metastasis. DNA methylation and histone modification are the most important manifestations of epigenetics in prostate cancer. The mechanisms of carcinogenesis of DNA methylation include whole-genome hypomethylation, aberrant local hypermethylation of promoters and genomic instability. DNA methylation is closely related to the process of prostate cancer, as in DNA damage repair, hormone response, tumor cell invasion/metastasis, cell cycle regulation, and so on. Histone modification causes corresponding changes in chromosome structure and the level of gene transcription, and it may affect the cycle, differentiation and apoptosis of cells, resulting in prostate cancer. Some therapies have been developed targeting the epigenetic changes in prostate cancer, including DNA methyltransferases and histone deacetylase inhibitors, and have achieved certain desirable results.

Molecular innovations towards theranostics of aggressive prostate cancer

DTIC Science & Technology

2016-09-01

Xiankai Sun, PhD CONTRACTING ORGANIZATION: University of Texas Southwestern Medical Center Dallas, TX 75390-8542 REPORT DATE : September 2016 TYPE OF...number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE (DD-MM-YYYY) September 2016 2. REPORT TYPE Annual 3. DATES COVERED (From...Partner PI’s lab for the treatment of aggressive prostate cancer. To date , we have designed and synthesized the proposed bifunctional chelator

Activin type IB receptor signaling in prostate cancer cells promotes lymph node metastasis in a xenograft model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nomura, Masatoshi, E-mail: nomura@med.kyushu-u.ac.jp; Tanaka, Kimitaka; Wang, Lixiang

Highlights: Black-Right-Pointing-Pointer ActRIB signaling induces Snail and S100A4 expressions in prostate cancer cells. Black-Right-Pointing-Pointer The prostate cancer cell lines expressing an active form of ActRIB were established. Black-Right-Pointing-Pointer ActRIB signaling promotes EMT and lymph node metastasis in xenograft model. -- Abstract: Activin, a member of the transforming growth factor-{beta} family, has been known to be a growth and differentiating factor. Despite its pluripotent effects, the roles of activin signaling in prostate cancer pathogenesis are still unclear. In this study, we established several cell lines that express a constitutive active form of activin type IB receptor (ActRIBCA) in human prostate cancermore » cells, ALVA41 (ALVA-ActRIBCA). There was no apparent change in the proliferation of ALVA-ActRIBCA cells in vitro; however, their migratory ability was significantly enhanced. In a xenograft model, histological analysis revealed that the expression of Snail, a cell-adhesion-suppressing transcription factor, was dramatically increased in ALVA-ActRIBCA tumors, indicating epithelial mesenchymal transition (EMT). Finally, mice bearing ALVA-ActRIBCA cells developed multiple lymph node metastases. In this study, we demonstrated that ActRIBCA signaling can promote cell migration in prostate cancer cells via a network of signaling molecules that work together to trigger the process of EMT, and thereby aid in the aggressiveness and progression of prostate cancers.« less

Prostatic Lesions in Odontocete Cetaceans.

PubMed

Suárez-Santana, Cristian M; Sierra, Eva; Díaz-Delgado, Josue; Zucca, Daniele; de Quirós, Yara Bernaldo; Puig-Lozano, Raquel; Câmara, Nakita; De la Fuente, Jesús; de Los Monteros, Antonio Espinosa; Rivero, Miguel; Arbelo, Manuel; Fernández, Antonio

2018-05-01

The prostate is the only accessory male genital gland described in cetaceans. Although few studies describe the gross and histologic anatomy of the prostate in cetaceans, there is no information on pathological findings involving this organ. The prostate glands of 45 cetaceans, including 8 different odontocete species ( n = 44) and 1 mysticete, were evaluated. The main pathologic diagnoses were verminous prostatitis, septic prostatitis, viral prostatitis, benign prostatic hyperplasia, and prostatitis of unknown etiology. Verminous prostatitis ( n = 12) was caused by nematodes of the genus Crassicauda, and different presentations were observed. Septic prostatitis, identified in 2 cases, both involved nematode infestation and Clostridium spp coinfection. One case of viral prostatitis was identified and was associated with morbillivirus infection. In prostatitis of unknown cause ( n = 7), varying degrees of prostatic lesions, mostly chronic inflammation, were identified. Impacts at individual levels (eg, localized disease, loss of reproductive capacity) and population levels (eg, decreased reproductive success) are plausible. Our results indicate a high occurrence of prostatic lesions in free-ranging odontocetes. For this reason, the prostate should be routinely inspected and sampled during necropsy of odontocete cetaceans.

New developments in the diagnosis and treatment of chronic prostatitis/chronic pelvic pain syndrome.

PubMed

Pontari, Michel; Giusto, Laura

2013-11-01

To describe new developments in the diagnosis and treatment of chronic prostatitis/chronic pelvic pain syndrome (CPPS). Symptoms in men with chronic prostatitis/CPPS appear to cluster into a group with primarily pelvic or localized disease, and a group with more systemic symptoms. Several other chronic pain conditions can be associated with chronic prostatitis/CPPS, including irritable bowel syndrome, fibromyalgia, and chronic fatigue syndrome. Markers of neurologic inflammation and autoimmune disease parallel changes in symptoms after treatment. Treatment options include new alpha-blockers, psychological intervention, and prostate-directed therapy. The areas of acupuncture and pelvic floor physical therapy/myofascial release have received increased recent attention and appear to be good options in these patients. Future therapy may include antibodies to mediators of neurogenic inflammation and even treatment of bacteria in the bowel. The diagnosis of chronic prostatitis/CPPS must include conditions traditionally outside the scope of urologic practice but important for the care of men with chronic pelvic pain. The treatment is best done using multiple simultaneous therapies aimed at the different aspects of the condition.

Impact of extended prostate biopsy including apical anterior region for cancer detection and prediction of surgical margin status for radical prostatectomy.

PubMed

Hashimoto, Kohei; Shinkai, Nobuo; Tanaka, Toshiaki; Masumori, Naoya

2017-06-01

We investigated diagnostic yield of initial biopsy and repeated biopsy including apical cores. We investigated 573 consecutive men with PSA of ≤20 ng/ml who underwent prostate biopsy between 2004 and 2013. The initial 14-core biopsy consisted of the sextant type, lateral sites at the base and middle, lateral apices (la) at anterior horn sites, and apical anterior sites (aa). The repeated 18-core biopsy consisted of the initial 14-core biopsy with four transition zone (TZ) sites at the base (tzb) and middle (tzm). Prostate cancer was diagnosed in 178 (38.9%) of 458 men with the initial 14-core biopsy, and 44 (38.3%) of 115 men with the repeated 18-core biopsy. In the initial biopsy setting, the unique cancer detection rate was high in apical sites (apex, la, and aa: 6.2%, 6.2% and 5.1%, respectively). In the repeated setting, it was high in the TZ site in addition to the apical site (apex, la, aa, tzm, and tzb: 6.8%, 6.8%, 11.4%, 9.1% and 11.4%, respectively). The positive SM rate at the apex was higher in patients whose cancer was detected only in sites other than the sextant region than for those in the sextant region (36.4% vs. 14.8%, P = 0.037). The initial 14-core and the repeated 18-core biopsy scheme including apical anterior cores are feasible for prostate cancer detection. We propose that apical biopsy cores can be used to predict not only the existence of cancer but also surgical margin status at the apex. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The Non-Gaussian Nature of Prostate Motion Based on Real-Time Intrafraction Tracking

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Yuting; Liu, Tian; Yang, Wells

2013-10-01

Purpose: The objective of this work is to test the validity of the Gaussian approximation for prostate motion through characterization of its spatial distribution. Methods and Materials: Real-time intrafraction prostate motion was observed using Calypso 4-dimensional (4D) nonradioactive electromagnetic tracking system. We report the results from a total of 1024 fractions from 31 prostate cancer patients. First, the correlation of prostate motion in right/left (RL), anteroposterior (AP), and superoinferior (SI) direction were determined using Pearson's correlation of coefficient. Then the spatial distribution of prostate motion was analyzed for individual fraction, individual patient including all fractions, and all patients including allmore » fractions. The displacement in RL, AP, SI, oblique, or total direction is fitted into a Gaussian distribution, and a Lilliefors test was used to evaluate the validity of the hypothesis that the displacement is normally distributed. Results: There is high correlation in AP/SI direction (61% of fractions with medium or strong correlation). This is consistent with the longitudinal oblique motion of the prostate, and likely the effect from respiration on an organ confined within the genitourinary diaphragm with the rectum sitting posteriorly and bladder sitting superiorly. In all directions, the non-Gaussian distribution is more common for individual fraction, individual patient including all fractions, and all patients including all fractions. The spatial distribution of prostate motion shows an elongated shape in oblique direction, indicating a higher range of motion in the AP and SI directions. Conclusions: Our results showed that the prostate motion is highly correlated in AP and SI direction, indicating an oblique motion preference. In addition, the spatial distribution of prostate motion is elongated in an oblique direction, indicating that the organ motion dosimetric modeling using Gaussian kernel may need to be modified to account for the particular organ motion character of prostate.« less

The non-Gaussian nature of prostate motion based on real-time intrafraction tracking.

PubMed

Lin, Yuting; Liu, Tian; Yang, Wells; Yang, Xiaofeng; Khan, Mohammad K

2013-10-01

The objective of this work is to test the validity of the Gaussian approximation for prostate motion through characterization of its spatial distribution. Real-time intrafraction prostate motion was observed using Calypso 4-dimensional (4D) nonradioactive electromagnetic tracking system. We report the results from a total of 1024 fractions from 31 prostate cancer patients. First, the correlation of prostate motion in right/left (RL), anteroposterior (AP), and superoinferior (SI) direction were determined using Pearson's correlation of coefficient. Then the spatial distribution of prostate motion was analyzed for individual fraction, individual patient including all fractions, and all patients including all fractions. The displacement in RL, AP, SI, oblique, or total direction is fitted into a Gaussian distribution, and a Lilliefors test was used to evaluate the validity of the hypothesis that the displacement is normally distributed. There is high correlation in AP/SI direction (61% of fractions with medium or strong correlation). This is consistent with the longitudinal oblique motion of the prostate, and likely the effect from respiration on an organ confined within the genitourinary diaphragm with the rectum sitting posteriorly and bladder sitting superiorly. In all directions, the non-Gaussian distribution is more common for individual fraction, individual patient including all fractions, and all patients including all fractions. The spatial distribution of prostate motion shows an elongated shape in oblique direction, indicating a higher range of motion in the AP and SI directions. Our results showed that the prostate motion is highly correlated in AP and SI direction, indicating an oblique motion preference. In addition, the spatial distribution of prostate motion is elongated in an oblique direction, indicating that the organ motion dosimetric modeling using Gaussian kernel may need to be modified to account for the particular organ motion character of prostate. Copyright © 2013 Elsevier Inc. All rights reserved.

Prostate Cancer

MedlinePlus

... man's bladder that produces fluid for semen. Prostate cancer is common among older men. It is rare ... younger than 40. Risk factors for developing prostate cancer include being over 65 years of age, family ...

Quantitative Proteomic Profiling of Prostate Cancer Reveals a Role for miR-128 in Prostate Cancer*

PubMed Central

Khan, Amjad P.; Poisson, Laila M.; Bhat, Vadiraja B.; Fermin, Damian; Zhao, Rong; Kalyana-Sundaram, Shanker; Michailidis, George; Nesvizhskii, Alexey I.; Omenn, Gilbert S.; Chinnaiyan, Arul M.; Sreekumar, Arun

2010-01-01

Multiple, complex molecular events characterize cancer development and progression. Deciphering the molecular networks that distinguish organ-confined disease from metastatic disease may lead to the identification of biomarkers of cancer invasion and disease aggressiveness. Although alterations in gene expression have been extensively quantified during neoplastic progression, complementary analyses of proteomic changes have been limited. Here we interrogate the proteomic alterations in a cohort of 15 prostate-derived tissues that included five each from adjacent benign prostate, clinically localized prostate cancer, and metastatic disease from distant sites. The experimental strategy couples isobaric tags for relative and absolute quantitation with multidimensional liquid phase peptide fractionation followed by tandem mass spectrometry. Over 1000 proteins were quantified across the specimens and delineated into clinically localized and metastatic prostate cancer-specific signatures. Included in these class-specific profiles were both proteins that were known to be dysregulated during prostate cancer progression and new ones defined by this study. Enrichment analysis of the prostate cancer-specific proteomic signature, to gain insight into the functional consequences of these alterations, revealed involvement of miR-128-a/b regulation during prostate cancer progression. This finding was validated using real time PCR analysis for microRNA transcript levels in an independent set of 15 clinical specimens. miR-128 levels were elevated in benign prostate epithelial cell lines compared with invasive prostate cancer cells. Knockdown of miR-128 induced invasion in benign prostate epithelial cells, whereas its overexpression attenuated invasion in prostate cancer cells. Taken together, our profiles of the proteomic alterations of prostate cancer progression revealed miR-128 as a potentially important negative regulator of prostate cancer cell invasion. PMID:19955085

SRD5A1 Genetic Variation and Prostate Cancer Epidemiology

DTIC Science & Technology

2006-05-01

DAMD17-03-1-0136 TITLE: SRD5A1 Genetic Variation and Prostate Cancer Epidemiology PRINCIPAL INVESTIGATOR: Troy Phipps...DATES COVERED (From - To) 1 May 2003 – 30 Apr 2006 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER SRD5A1 Genetic Variation and Prostate Cancer...Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The human steroid 5-alpha reductase type I ( SRD5A1 ) gene was sequenced in 101

Prediction of individual genetic risk to prostate cancer using a polygenic score.

PubMed

Szulkin, Robert; Whitington, Thomas; Eklund, Martin; Aly, Markus; Eeles, Rosalind A; Easton, Douglas; Kote-Jarai, Z Sofia; Amin Al Olama, Ali; Benlloch, Sara; Muir, Kenneth; Giles, Graham G; Southey, Melissa C; Fitzgerald, Liesel M; Henderson, Brian E; Schumacher, Fredrick; Haiman, Christopher A; Schleutker, Johanna; Wahlfors, Tiina; Tammela, Teuvo L J; Nordestgaard, Børge G; Key, Tim J; Travis, Ruth C; Neal, David E; Donovan, Jenny L; Hamdy, Freddie C; Pharoah, Paul; Pashayan, Nora; Khaw, Kay-Tee; Stanford, Janet L; Thibodeau, Stephen N; McDonnell, Shannon K; Schaid, Daniel J; Maier, Christiane; Vogel, Walther; Luedeke, Manuel; Herkommer, Kathleen; Kibel, Adam S; Cybulski, Cezary; Lubiński, Jan; Kluźniak, Wojciech; Cannon-Albright, Lisa; Brenner, Hermann; Butterbach, Katja; Stegmaier, Christa; Park, Jong Y; Sellers, Thomas; Lin, Hui-Yi; Lim, Hui-Yi; Slavov, Chavdar; Kaneva, Radka; Mitev, Vanio; Batra, Jyotsna; Clements, Judith A; Spurdle, Amanda; Teixeira, Manuel R; Paulo, Paula; Maia, Sofia; Pandha, Hardev; Michael, Agnieszka; Kierzek, Andrzej; Gronberg, Henrik; Wiklund, Fredrik

2015-09-01

Polygenic risk scores comprising established susceptibility variants have shown to be informative classifiers for several complex diseases including prostate cancer. For prostate cancer it is unknown if inclusion of genetic markers that have so far not been associated with prostate cancer risk at a genome-wide significant level will improve disease prediction. We built polygenic risk scores in a large training set comprising over 25,000 individuals. Initially 65 established prostate cancer susceptibility variants were selected. After LD pruning additional variants were prioritized based on their association with prostate cancer. Six-fold cross validation was performed to assess genetic risk scores and optimize the number of additional variants to be included. The final model was evaluated in an independent study population including 1,370 cases and 1,239 controls. The polygenic risk score with 65 established susceptibility variants provided an area under the curve (AUC) of 0.67. Adding an additional 68 novel variants significantly increased the AUC to 0.68 (P = 0.0012) and the net reclassification index with 0.21 (P = 8.5E-08). All novel variants were located in genomic regions established as associated with prostate cancer risk. Inclusion of additional genetic variants from established prostate cancer susceptibility regions improves disease prediction. © 2015 Wiley Periodicals, Inc.

Stem cell and neurogenic gene-expression profiles link prostate basal cells to aggressive prostate cancer

PubMed Central

Zhang, Dingxiao; Park, Daechan; Zhong, Yi; Lu, Yue; Rycaj, Kiera; Gong, Shuai; Chen, Xin; Liu, Xin; Chao, Hsueh-Ping; Whitney, Pamela; Calhoun-Davis, Tammy; Takata, Yoko; Shen, Jianjun; Iyer, Vishwanath R.; Tang, Dean G.

2016-01-01

The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here we describe a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep RNA sequencing. Through molecular and biological characterizations, we show that the differential gene-expression profiles account for their distinct functional properties. Strikingly, basal cells preferentially express gene categories associated with stem cells, neurogenesis and ribosomal RNA (rRNA) biogenesis. Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal cell gene-expression profile is enriched in advanced, anaplastic, castration-resistant and metastatic prostate cancers. Therefore, we link the cell-type-specific gene signatures to aggressive subtypes of prostate cancer and identify gene signatures associated with adverse clinical features. PMID:26924072

Stem cell and neurogenic gene-expression profiles link prostate basal cells to aggressive prostate cancer.

PubMed

Zhang, Dingxiao; Park, Daechan; Zhong, Yi; Lu, Yue; Rycaj, Kiera; Gong, Shuai; Chen, Xin; Liu, Xin; Chao, Hsueh-Ping; Whitney, Pamela; Calhoun-Davis, Tammy; Takata, Yoko; Shen, Jianjun; Iyer, Vishwanath R; Tang, Dean G

2016-02-29

The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here we describe a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep RNA sequencing. Through molecular and biological characterizations, we show that the differential gene-expression profiles account for their distinct functional properties. Strikingly, basal cells preferentially express gene categories associated with stem cells, neurogenesis and ribosomal RNA (rRNA) biogenesis. Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal cell gene-expression profile is enriched in advanced, anaplastic, castration-resistant and metastatic prostate cancers. Therefore, we link the cell-type-specific gene signatures to aggressive subtypes of prostate cancer and identify gene signatures associated with adverse clinical features.

BCL2 genotypes and prostate cancer survival.

PubMed

Renner, Wilfried; Langsenlehner, Uwe; Krenn-Pilko, Sabine; Eder, Petra; Langsenlehner, Tanja

2017-06-01

The antiapoptotic B‑cell lymphoma 2 (BCL2) gene is a key player in cancer development and progression. A functional single-nucleotide polymorphism (c.-938C>A, rs2279115) in the inhibitory P2 BCL2 gene promoter has been associated with clinical outcomes in various types of cancer. Aim of the present study was to analyze the role of BCL2-938C>A genotypes in prostate cancer mortality. The association between BCL2-938C>A (rs2279115) genotypes and prostate cancer outcome was studied within the prospective PROCAGENE study comprising 702 prostate cancer patients. During a median follow-up time of 92 months, 120 (17.1%) patients died. A univariate Cox regression model showed a significant association of the CC genotype with reduced cancer-specific survival (CSS; hazard ratio, HR, 2.13, 95% confidence interval, CI, 1.10-4.12; p = 0.024) and overall survival (OS; HR 2.34, 95% CI 1.58-3.47; p < 0.001). In a multivariate Cox regression model including age at diagnosis, risk group, and androgen deprivation therapy, the CC genotype remained a significant predictor of poor CSS (HR 2.05, 95% CI 1.05-3.99; p = 0.034) and OS (HR 2.25, 95% CI 1.51-3.36; p < 0.001). This study provides evidence that the homozygous BCL2-938 CC genotype is associated with OS and C in prostate cancer patients.

Increased Bisecting N-Acetylglucosamine and Decreased Branched Chain Glycans of N-linked Glycoproteins in Expressed Prostatic Secretions Associated with Prostate Cancer Progression

PubMed Central

Nyalwidhe, Julius O.; Betesh, Lucy R.; Powers, Thomas W.; Jones, E. Ellen; White, Krista Y.; Burch, Tanya C.; Brooks, Jasmin; Watson, Megan T.; Lance, Raymond S.; Troyer, Dean A.; Semmes, O. John; Mehta, Anand; Drake, Richard R.

2013-01-01

Purpose Using prostatic fluids rich in glycoproteins like prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) , the goal of this study was to identify the structural types and relative abundance of glycans associated with prostate cancer status for subsequent use in emerging mass spectrometry-based glycopeptide analysis platforms. Experimental Design A series of pooled samples of expressed prostatic secretions (EPS) and exosomes reflecting different stages of prostate cancer disease were used for N-linked glycan profiling by three complementary methods, MALDI-TOF profiling, normal-phase HPLC separation, and triple quadropole MS analysis of PAP glycopeptides. Results Glycan profiling of N-linked glycans from different EPS fluids indicated a global decrease in larger branched tri- and tetra-antennary glycans. Differential exoglycosidase treatments indicated a substantial increase in bisecting N-acetylglucosamines correlated with disease severity. A triple quadrupole MS analysis of the N-linked glycopeptides sites from PAP in aggressive prostate cancer pools was done to cross-reference with the glycan profiling data. Conclusion and clinical relevance Changes in glycosylation as detected in EPS fluids reflect the clinical status of prostate cancer. Defining these molecular signatures at the glycopeptide level in individual samples could improve current approaches of diagnosis and prognosis. PMID:23775902

Fisetin Enhances Chemotherapeutic Effect of Cabazitaxel against Human Prostate Cancer Cells.

PubMed

Mukhtar, Eiman; Adhami, Vaqar Mustafa; Siddiqui, Imtiaz Ahmad; Verma, Ajit Kumar; Mukhtar, Hasan

2016-12-01

Although treatment of prostate cancer has improved over the past several years, taxanes, such as cabazitaxel, remain the only form of effective chemotherapy that improves survival in patients with metastatic castration-resistant prostate cancer. However, the effectiveness of this class of drugs has been associated with various side effects and drug resistance. We previously reported that fisetin, a hydroxyflavone, is a microtubule-stabilizing agent and inhibits prostate cancer cell proliferation, migration, and invasion and suggested its use as an adjuvant for treatment of prostate and other cancer types. In this study, we investigated the effect of fisetin in combination with cabazitaxel with the objective to achieve maximum therapeutic benefit, reduce dose and toxicity, and minimize or delay the induction of drug resistance and metastasis. Our data show for the first time that a combination of fisetin (20 μmol/L) enhances cabazitaxel (5 nmol/L) and synergistically reduces 22Rν1, PC-3M-luc-6, and C4-2 cell viability and metastatic properties with minimal adverse effects on normal prostate epithelial cells. In addition, the combination of fisetin with cabazitaxel was associated with inhibition of proliferation and enhancement of apoptosis. Furthermore, combination treatment resulted in the inhibition of tumor growth, invasion, and metastasis when assessed in two in vivo xenograft mouse models. These results provide evidence that fisetin may have therapeutic benefit for patients with advanced prostate cancer through enhancing the efficacy of cabazitaxel under both androgen-dependent and androgen-independent conditions. This study underscores the benefit of the combination of fisetin with cabazitaxel for the treatment of advanced and resistant prostate cancer and possibly other cancer types. Mol Cancer Ther; 15(12); 2863-74. ©2016 AACR. ©2016 American Association for Cancer Research.

Assessment of the quality of medical care among patients with early stage prostate cancer undergoing expectant management in the United States.

PubMed

Ritchey, Jamie; Gay, E Greer; Spencer, Benjamin A; Miller, David C; Wallner, Lauren P; Stewart, Andrew K; Dunn, Rodney L; Litwin, Mark S; Wei, John T

2012-09-01

Given the increased attention to the quality and cost of medical care, the Institute of Medicine and Centers for Medicare and Medicaid Services have called for performance measurement and reporting. The clinical management of prostate cancer has been outlined, yet is not intended to describe quality prostate cancer care. Therefore, RAND researchers developed quality indicators for early stage prostate cancer. The ACoS (American College of Surgeons) used these indicators to perform the first national assessment to our knowledge of the quality of care among men with early stage prostate cancer undergoing expectant management. Information from medical records was abstracted for evidence of compliance with the RAND indicators (structure and process). Weighted and stratified proportions were calculated to assess indicator compliance. Logistic regression models were fit and evaluated by hospital type and patient factors. A weighted and stratified total of 13,876 early stage prostate cancer cases on expectant management in 2000 to 2001 were investigated. Compliance with structural indicators was high (greater than 80%) and compliance with process indicators varied (19% to 87%). Differences in process indicators were observed from models by hospital type and comorbid conditions, but not for age, race or insurance status. Using the RAND quality indicators this study revealed several process areas for quality improvement among men with early stage prostate cancer on expectant management in the United States. Efforts to improve the quality of early stage prostate cancer care need to move beyond the paradigm of age, race and insurance status. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vilches, J.; Lopez, A.; De Palacio, L.

Calculi removed from human prostates affected with nodular hyperplasia were analyzed with scanning electron microscopy and EDAX system. The general spectrum was made up of Na, Al, Mg, S, P, Ca and Zn. Two types of stone were identified morphostructurally and microanalytically: calculi type I of nodular surface with high peaks of S, and calculi type II polyfaceted with high peaks of P and Ca. Their formation from corpora amylacea and/or exogenous constituents is discussed. The superficial deposit of Zn suggests its incorporation from the prostatic liquid and does not seem to play an important role in the genesis.

Structure and Function of the Splice Variants of TMPRSS2-ERG, a Prevalent Genomic Alteration in Prostate Cancer

DTIC Science & Technology

2009-09-01

binding ETS domain) and five type II (without ETS domain). Fusion-positive type I– and type II–containing phages were amplified with T3 and T7 primers...will be performed to identify the authentic 3’ UTRs from the mRNA pool from CaP patient specimens. Using phage excision strategy, we will use to... phage DNA sequences plasmids (cDNA) clones were generated by using phage excision strategy. Figure 1. ERG splice variants in prostate cancer

Camel heavy chain antibodies against prostate-specific membrane antigen.

PubMed

Evazalipour, Mehdi; Tehrani, Bahram Soltani; Abolhassani, Mohsen; Morovvati, Hamid; Omidfar, Kobra

2012-12-01

Prostate-specific membrane antigen (PSMA), a type II integral membrane glycoprotein, is highly overexpressed in all forms of prostate cancer tissues. It has also been demonstrated in a wide range of neovasculature of non-prostatic solid tumors, including bladder, pancreas, lung, kidney, colorectal, and gastric cancers. Given the unique expression of PSMA, it is considered an alluring target for antibody-based imaging and therapy of cancer. In the present study, the production and characterization of camel heavy chain antibodies (HCAbs) specific for the external domain of the PSMA are reported. Due to the absence of the CH1 domain, HCAbs are smaller than their counterparts in conventional antibodies. In this study, camel antibodies were generated through immunization of Camelus dromedarius with a synthetic 28 amino acid peptide corresponding to the external surface domain of antigen and PSMA-expressing cell lines. Different binding properties to protein A and protein G affinity columns were deployed to separate three subclasses of camel IgG. The affinity purified HCAbs bound selectively to the synthetic peptide in enzyme linked immunosorbent assay (ELISA) and reacted specifically with PSMA-expressing cell line through immunocytochemistry study. Currently, we are attempting to develop recombinant variable domain of these heavy chain antibodies (VHH or nanobody) for tumor imaging and cancer therapy.

Potent 19-norvitamin D analogs for prostate and liver cancer therapy

PubMed Central

Kittaka, Atsushi; Yoshida, Akihiro; Chiang, Kun-Chun; Takano, Masashi; Sawada, Daisuke; Sakaki, Toshiyuki; Chen, Tai C

2013-01-01

The active form of vitamin D3, 1α,25(OH)2D3 or calcitriol, is known to inhibit the proliferation and invasiveness of many types of cancer cells, including prostate and liver cancer cells. These findings support the use of 1α,25(OH)2D3 for prostate and liver cancer therapy. However, 1α,25(OH)2D3 can cause hypercalcemia, thus, analogs of 1α,25(OH)2D3 that are less calcemic but exhibit potent antiproliferative activity would be attractive as therapeutic agents. We have developed 2α-functional group substituted 19-norvitamin D3 analogs with and without 14-epimerization. Among them, 2α- and 2β-(3-hydroxypropyl)-1α,25-dihydroxy-19-norvitamin D3 (MART-10 and -11, respectively) and 14-epi-2α- and 14-epi-2β-(3-hydroxypropyl)-1α,25-dihydroxy-19-norvitamin D3 (14-epi-MART-10 and 14-epi-MART-11, respectively) were found to be the most promising. In this review, we discuss the synthesis of this unique class of vitamin D analogs, the molecular mechanism of anticancer actions of vitamin D, and the biological evaluation of these analogs for potential application to the prevention and treatment of prostate and liver cancer. PMID:23157238

Radiation-Induced Immunogenic Modulation Enhances T-Cell Killing | Center for Cancer Research

Cancer.gov

For many types of cancer, including breast, lung, and prostate carcinomas, radiation therapy is the standard of care. However, limits placed on the tolerable levels of radiation exposure coupled with heterogeneity of biological tissue result in cases where not all tumor cells receive a lethal dose of radiation. Preclinical studies have shown that exposing tumor cells to lethal

Comparison of the complications of traditional 12 cores transrectal prostate biopsy with image fusion guided transperineal prostate biopsy.

PubMed

Huang, Haifeng; Wang, Wei; Lin, Tingsheng; Zhang, Qing; Zhao, Xiaozhi; Lian, Huibo; Guo, Hongqian

2016-11-17

To compare the complications of traditional transrectal (TR) prostate biopsy and image fusion guided transperineal (TP) prostate biopsy in our center. Two hundred and fourty-two patients who underwent prostate biopsy from August 2014 to January 2015were reviewed. Among them, 144 patients underwent systematic 12-core transrectal ultrasonography (TRUS) guided prostate biopsy (TR approach) while 98 patients underwent free-hand transperineal targeted biopsy with TRUS and multi-parameter magnetic resonance imaging (mpMRI) fusion images (TP approach). The complications of the two groups were presented and a simple statistical analysis was performed to compare the two groups. The cohort of our study include242 patients, including 144 patients underwent TR biopsies while 98 patients underwentTP biopsies. There was no significant difference of major complications, including sepsis, bleeding and other complication requiring admissionbetween the two groups (P > 0.05). The incidence rate of infection and rectal bleeding in TR was much higher than TP (p < 0.05), but the incidence rate of perineal swelling in TP was much higher than TR (p < 0.05). There were no significant differences of minor complications including hematuria, lower urinary tract symptoms (LUTS), dysuria, and acuteurinary retention between the two groups (p > 0.05). The present study supports the safety of both techniques. Free-handTP targeted prostate biopsy with real-time fusion imaging of mpMRI and TR ultrasound is a good approach for prostate biopsy.

SYSTEMS MODELING OF PROSTATE REGULATION AND ...

EPA Pesticide Factsheets

The prostate is an androgen-dependent tissue that is an important site of disease in human males as well as an important indicator of androgen status in animals. The rat prostate is used for studying antiandrogenic drugs as well as for evaluation of endocrine disruption (e.g., Hershberger Assay). Pubertal changes in the prostate have been observed to be as sensitive to environmental antiandrogens as in utero effects. The goal of this research is to model the biology of prostate androgen function on a systems level to determine the factors responsible for the dose-response observable with androgens and antiandrogens in the male rat. This includes investigation of the roles of positive and negative feedback loops in prostatic response following castration and dosing with testosterone and/or antiandrogens. A biologically-based, systems-level model will be developed describing the regulation of the prostate by androgens. The model will extend an existing model for the male rat central axis, which describes feedback between luteinizing hormone and testosterone production in the testes, to include the prostate and conversion of testosterone to dihydrotestosterone (DHT). The prostate model will describe binding of androgens to the androgen receptor, 5α-reductase catalyzed production of DHT, and gene regulation affecting cell proliferation, apoptosis, and prostatic fluid production. The model will combine pharmacokinetic models for endogenous hormones (i.e., testost

Acute Bacterial Prostatitis: Diagnosis and Management.

PubMed

Coker, Timothy J; Dierfeldt, Daniel M

2016-01-15

Acute bacterial prostatitis is an acute infection of the prostate gland that causes pelvic pain and urinary tract symptoms, such as dysuria, urinary frequency, and urinary retention, and may lead to systemic symptoms, such as fevers, chills, nausea, emesis, and malaise. Although the true incidence is unknown, acute bacterial prostatitis is estimated to comprise approximately 10% of all cases of prostatitis. Most acute bacterial prostatitis infections are community acquired, but some occur after transurethral manipulation procedures, such as urethral catheterization and cystoscopy, or after transrectal prostate biopsy. The physical examination should include abdominal, genital, and digital rectal examination to assess for a tender, enlarged, or boggy prostate. Diagnosis is predominantly made based on history and physical examination, but may be aided by urinalysis. Urine cultures should be obtained in all patients who are suspected of having acute bacterial prostatitis to determine the responsible bacteria and its antibiotic sensitivity pattern. Additional laboratory studies can be obtained based on risk factors and severity of illness. Radiography is typically unnecessary. Most patients can be treated as outpatients with oral antibiotics and supportive measures. Hospitalization and broad-spectrum intravenous antibiotics should be considered in patients who are systemically ill, unable to voluntarily urinate, unable to tolerate oral intake, or have risk factors for antibiotic resistance. Typical antibiotic regimens include ceftriaxone and doxycycline, ciprofloxacin, and piperacillin/tazobactam. The risk of nosocomial bacterial prostatitis can be reduced by using antibiotics, such as ciprofloxacin, before transrectal prostate biopsy.

Beyond the androgen receptor II: New approaches to understanding and treating metastatic prostate cancer; Report from the 2017 Coffey-Holden Prostate Cancer Academy Meeting.

PubMed

Miyahira, Andrea K; Cheng, Heather H; Abida, Wassim; Ellis, Leigh; Harshman, Lauren C; Spratt, Daniel E; Simons, Jonathan W; Pienta, Kenneth J; Soule, Howard R

2017-11-01

The 2017 Coffey-Holden Prostate Cancer Academy (CHPCA) Meeting, "Beyond the Androgen Receptor II: New Approaches to Understanding and Treating Metastatic Prostate Cancer," was held in Carlsbad, California from June 14-17, 2017. The CHPCA is an annual scientific conference hosted by the Prostate Cancer Foundation (PCF) that is uniquely designed to produce extensive and constructive discussions on the most urgent and impactful topics concerning research into the biology and treatment of metastatic prostate cancer. The 2017 CHPCA Meeting was the 5th meeting in this annual series and was attended by 71 investigators focused on prostate cancer and a variety of other fields including breast and ovarian cancer. The discussions at the meeting were concentrated on topics areas including: mechanisms and therapeutic approaches for molecular subclasses of castrate resistant prostate cancer (CRPC), the epigenetic landscape of prostate cancer, the role of DNA repair gene mutations, advancing the use of germline genetics in clinical practice, radionuclides for imaging and therapy, advances in molecular imaging, and therapeutic strategies for successful use of immunotherapy in advanced prostate cancer. This article reviews the presentations and discussions from the 2017 CHPCA Meeting in order to disseminate this knowledge and accelerate new biological understandings and advances in the treatment of patients with metastatic prostate cancer. © 2017 Wiley Periodicals, Inc.

Augmentation of the anticancer activity of CYT997 in human prostate cancer by inhibiting Src activity.

PubMed

Teng, Yong; Cai, Yafei; Pi, Wenhu; Gao, Lixia; Shay, Chloe

2017-06-12

Abnormalities of tubulin polymerization and microtubule assembly are often seen in cancer, which make them very suitable targets for the development of therapeutic approach against rapidly dividing and aggressive cancer cells. CYT997 is a novel microtubule-disrupting agent with anticancer activity in multiple cancer types including prostate cancer. However, the molecular mechanisms of action of CYT997 in prostate cancer have not been well characterized. Src knockdown cells were achieved by lentiviral-mediated interference. The drug effects on cell proliferation were measured by MTS. The drug effects on cell viability and death were determined by Cell Titer-Glo® Luminescent cell viability kit and flow cytometry with Zombie Aqua™ staining. The drug effects on apoptosis were assessed by Cell Death Detection Elisa kit and Western blot with a cleaved PARP antibody. The drug effects on cell invasion were examined by Matrigel-coated Boyden chambers. Oxidative stress was detected by DCFH-DA staining and electrochemical biosensor. Mouse models generated by subcutaneous or intracardiac injection were used to investigate the in vivo drug efficacy in tumor growth and metastasis. CYT997 effectively inhibited proliferation, survival, and invasion of prostate cancer cells via blocking multiple oncogenic signaling cascades but not the Src pathway. Inhibition of Src expression by small hairpin RNA or inactivation of Src by dasatinib increased the CYT997-induced cytotoxicity of in vitro. Moreover, the combination of dasatinib and CYT997 exhibited a superior inhibitory effect on tumor growth and metastasis compared with either of the drugs alone. Our findings demonstrate that blockage of Src augments the anticancer effect of CYT997 on prostate cancer and suggest that co-treatment of dasatinib and CYT997 may represent an effective therapeutic regimen for limiting prostate cancer.

Does the association of prostate cancer with night-shift work differ according to rotating vs. fixed schedule? A systematic review and meta-analysis.

PubMed

Mancio, Jennifer; Leal, Cátia; Ferreira, Marta; Norton, Pedro; Lunet, Nuno

2018-04-27

Recent studies suggested that the relation between night-shift work and prostate cancer may differ between rotating and fixed schedules. We aimed to quantify the independent association between night-shift work and prostate cancer, for rotating and fixed schedules. We searched MEDLINE for studies assessing the association of night-shift work, by rotating or fixed schedules, with prostate cancer. We computed summary relative risk (RR) estimates with 95% confidence intervals (95% CI) using the inverse variance method and quantified heterogeneity using the I 2 statistic. Meta-regression analysis was used to compare the summary RR estimates for rotating and fixed schedules, while reducing heterogeneity. A total of nine studies assessed the effect of rotating and, in addition, four of them provided the effect of fixed night-shift work, in relation to daytime workers. Rotating night-shift work was associated with a significantly increased risk of prostate cancer (RR = 1.06, 95% CI of 1.01 to 1.12; I 2  = 50%), but not fixed night-shift work (RR of 1.01, 95% CI of 0.81 to 1.26; I 2  = 33%). In meta-regression model including study design, type of population, and control of confounding, the summary RR was 20% higher for rotating vs. fixed schedule, with heterogeneity fully explained by these variables. This is the first meta-analysis suggesting that an increased risk of prostate cancer may be restricted to workers with rotating night shifts. However, the association was weak and additional studies are needed to further clarify this relation before it can be translated into measures for risk reduction in occupational settings.

The pluripotency factor Nanog is directly upregulated by the androgen receptor in prostate cancer cells.

PubMed

Kregel, Steven; Szmulewitz, Russell Z; Vander Griend, Donald J

2014-11-01

The Androgen Receptor (AR) is a nuclear hormone receptor that functions as a critical oncogene in all stages of prostate cancer progression, including progression to castration-resistance following androgen-deprivation therapy. Thus, identifying and targeting critical AR-regulated genes is one potential method to block castration-resistant cancer proliferation. Of particular importance are transcription factors that regulate stem cell pluripotency; many of these genes are emerging as critical oncogenes in numerous tumor cell types. Of these, Nanog has been previously shown to increase the self-renewal and stem-like properties of prostate cancer cells. Thus, we hypothesized that Nanog is a candidate AR target gene that may impart castration-resistance. We modulated AR signaling in LNCaP prostate cancer cells and assayed for Nanog expression. Direct AR binding to the NANOG promoter was tested using AR Chromatin Immunoprecipation (ChIP) and analyses of publically available AR ChIP-sequencing data-sets. Nanog over-expressing cells were analyzed for cell growth and cytotoxicity in response to the AR antagonist enzalutamide and the microtubule stabilizing agent docetaxel. AR signaling upregulates Nanog mRNA and protein. AR binds directly to the NANOG promoter, and was not identified within 75 kb of the NANOGP8 pseudogene, suggesting the NANOG gene locus was preferentially activated. Nanog overexpression in LNCaP cells increases overall growth, but does not increase resistance to enzalutamide or docetaxel. Nanog is a novel oncogenic AR target gene in prostate cancer cells, and stable expression of Nanog increases proliferation and growth of prostate cancer cells, but not resistance to enzalutamide or docetaxel. © 2014 Wiley Periodicals, Inc.

Testing the circadian gene hypothesis in prostate cancer: a population-based case-control study

PubMed Central

Zhu, Yong; Stevens, Richard G.; Hoffman, Aaron E.; FitzGerald, Liesel M.; Kwon, Erika M.; Ostrander, Elaine A.; Davis, Scott; Zheng, Tongzhang; Stanford, Janet L.

2010-01-01

Circadian genes are responsible for maintaining the ancient adaptation of a 24-hour circadian rhythm and influence a variety of cancer-related biological pathways, including the regulation of sex hormone levels. However, few studies have been undertaken to investigate the role of circadian genes in the development of prostate cancer, the most common cancer type among men (excluding non-melanoma skin cancer). The current genetic association study tested the circadian gene hypothesis in relation to prostate cancer by genotyping a total of 41 tagging and amino acid altering SNPs in ten circadian-related genes in a population-based case-control study of Caucasian men (N=1,308 cases and 1,266 controls). Our results showed that at least one SNP in nine core circadian genes (rs885747 and rs2289591 in PER1, rs7602358 in PER2, rs1012477 in PER3, rs1534891 in CSNK1E, rs12315175 in CRY1, rs2292912 in CRY2, rs7950226 in ARNTL, rs11133373 in CLOCK, and rs1369481, rs895521, and rs17024926 in NPAS2) was significantly associated with susceptibility to prostate cancer (either overall risk or risk of aggressive disease), and the risk estimate for four SNPs in three genes (rs885747 and rs2289591 in PER1, rs1012477 in PER3 and rs11133373 in CLOCK) varied by disease aggressiveness. Further analyses of haplotypes were consistent with these genotyping results. Findings from this candidate gene association study support the hypothesis of a link between genetic variants in circadian genes and prostate cancer risk, warranting further confirmation and mechanistic investigation of circadian biomarkers in prostate tumorigenesis. PMID:19934327

IL17 Mediates Pelvic Pain in Experimental Autoimmune Prostatitis (EAP).

PubMed

Murphy, Stephen F; Schaeffer, Anthony J; Done, Joseph; Wong, Larry; Bell-Cohn, Ashlee; Roman, Kenny; Cashy, John; Ohlhausen, Michelle; Thumbikat, Praveen

2015-01-01

Chronic pelvic pain syndrome (CPPS) is the most common form of prostatitis, accounting for 90-95% of all diagnoses. It is a complex multi-symptom syndrome with unknown etiology and limited effective treatments. Previous investigations highlight roles for inflammatory mediators in disease progression by correlating levels of cytokines and chemokines with patient reported symptom scores. It is hypothesized that alteration of adaptive immune mechanisms results in autoimmunity and subsequent development of pain. Mouse models of CPPS have been developed to delineate these immune mechanisms driving pain in humans. Using the experimental autoimmune prostatitis (EAP) in C57BL/6 mice model of CPPS we examined the role of CD4+T-cell subsets in the development and maintenance of prostate pain, by tactile allodynia behavioral testing and flow cytometry. In tandem with increased CD4+IL17A+ T-cells upon EAP induction, prophylactic treatment with an anti-IL17 antibody one-day prior to EAP induction prevented the onset of pelvic pain. Therapeutic blockade of IL17 did not reverse pain symptoms indicating that IL17 is essential for development but not maintenance of chronic pain in EAP. Furthermore we identified a cytokine, IL7, to be associated with increased symptom severity in CPPS patients and is increased in patient prostatic secretions and the prostates of EAP mice. IL7 is fundamental to development of IL17 producing cells and plays a role in maturation of auto-reactive T-cells, it is also associated with autoimmune disorders including multiple sclerosis and type-1 diabetes. More recently a growing body of research has pointed to IL17's role in development of neuropathic and chronic pain. This report presents novel data on the role of CD4+IL17+ T-cells in development and maintenance of pain in EAP and CPPS.

Multifunctional iron platinum stealth immunomicelles: targeted detection of human prostate cancer cells using both fluorescence and magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Taylor, Robert M.; Huber, Dale L.; Monson, Todd C.; Ali, Abdul-Mehdi S.; Bisoffi, Marco; Sillerud, Laurel O.

2011-10-01

Superparamagnetic iron oxide nanoparticles (SPIONs) are the most common type of contrast agents used in contrast agent-enhanced magnetic resonance imaging (MRI). Still, there is a great deal of room for improvement, and nanoparticles with increased MRI relaxivities are needed to increase the contrast enhancement in MRI applied to various medical conditions including cancer. We report the synthesis of superparamagnetic iron platinum nanoparticles (SIPPs) and subsequent encapsulation using PEGylated phospholipids to create stealth immunomicelles (DSPE-SIPPs) that can be specifically targeted to human prostate cancer cell lines and detected using both MRI and fluorescence imaging. SIPP cores and DSPE-SIPPs were 8.5 ± 1.6 nm and 42.9 ± 8.2 nm in diameter, respectively, and the SIPPs had a magnetic moment of 120 A m2/kg iron. J591, a monoclonal antibody against prostate specific membrane antigen (PSMA), was conjugated to the DSPE-SIPPs (J591-DSPE-SIPPs), and specific targeting of J591-DSPE-SIPPs to PSMA-expressing human prostate cancer cell lines was demonstrated using fluorescence confocal microscopy. The transverse relaxivity of the DSPE-SIPPs, measured at 4.7 Tesla, was 300.6 ± 8.5 s-1 mM-1, which is 13-fold better than commercially available SPIONs (23.8 ± 6.9 s-1 mM-1) and 3-fold better than reported relaxivities for Feridex® and Resovist®. Our data suggest that J591-DSPE-SIPPs specifically target human prostate cancer cells in vitro, are superior contrast agents in T 2-weighted MRI, and can be detected using fluorescence imaging. To our knowledge, this is the first report on the synthesis of multifunctional SIPP micelles and using SIPPs for the specific detection of prostate cancer.

Nc886 is epigenetically repressed in prostate cancer and acts as a tumor suppressor through the inhibition of cell growth.

PubMed

Fort, Rafael Sebastián; Mathó, Cecilia; Geraldo, Murilo Vieira; Ottati, María Carolina; Yamashita, Alex Shimura; Saito, Kelly Cristina; Leite, Katia Ramos Moreira; Méndez, Manuel; Maedo, Noemí; Méndez, Laura; Garat, Beatriz; Kimura, Edna Teruko; Sotelo-Silveira, José Roberto; Duhagon, María Ana

2018-02-02

Nc886 is a 102 bp non-coding RNA transcript initially classified as a microRNA precursor (Pre-miR-886), later as a divergent homologue of the vault RNAs (vtRNA 2-1) and more recently as a novel type of RNA (nc886). Although nc886/vtRNA2-1/Pre-miR-886 identity is still controversial, it was shown to be epigenetically controlled, presenting both tumor suppressor and oncogenic function in different cancers. Here, we study for the first time the role of nc886 in prostate cancer. Nc886 promoter methylation status and its correlation with patient clinical parameters or DNMTs levels were evaluated in TCGA and specific GEO prostate tissue datasets. Nc886 level was measured by RT-qPCR to compare normal/neoplastic prostate cells from radical prostatectomies and cell lines, and to assess nc886 response to demethylating agents. The effect of nc886 recovery in cell proliferation (in vitro and in vivo) and invasion (in vitro) was evaluated using lentiviral transduced DU145 and LNCaP cell lines. The association between the expression of nc886 and selected genes was analyzed in the TCGA-PRAD cohort. Nc886 promoter methylation increases in tumor vs. normal prostate tissue, as well as in metastatic vs. normal prostate tissue. Additionally, nc886 promoter methylation correlates with prostate cancer clinical staging, including biochemical recurrence, Clinical T-value and Gleason score. Nc886 transcript is downregulated in tumor vs. normal tissue -in agreement with its promoter methylation status- and increases upon demethylating treatment. In functional studies, the overexpression of nc886 in the LNCaP and DU145 cell line leads to a decreased in vitro cell proliferation and invasion, as well as a reduced in vivo cell growth in NUDE-mice tumor xenografts. Finally, nc886 expression associates with the prostate cancer cell cycle progression gene signature in TCGA-PRAD. Our data suggest a tumor suppressor role for nc886 in the prostate, whose expression is epigenetically silenced in cancer leading to an increase in cell proliferation and invasion. Nc886 might hold clinical value in prostate cancer due to its association with clinical parameters and with a clinically validated gene signature.

Lessons Learned from Implementing a Prostate Cancer Risk Assessment Program for Underserved High-Risk Men in the Community: the Prostate REACH Project.

PubMed

Fleisher, Linda; Davis, Stacy N; Gross, Laura; Bagden, Loretta; Zakrzewski, Debra; González, Evelyn; Kandadai, Venk; Rusten, Cheryl; Baskett, Jerilyn; Obeid, Elias; Giri, Veda N

2016-03-01

Prostate cancer disproportionately affects Black men, who may also encounter barriers to participation in prostate cancer risk assessment. The Prostate Risk, Education and Assessment in the Community with Help (REACH) project was a community-based extension of a comprehensive prostate cancer risk assessment program at a comprehensive cancer center. The goals of the REACH project were the following: (1) establish a community prostate cancer risk assessment clinic, (2) conduct targeted recruitment, and (3) provide navigation services including follow-up for uninsured men. Key implementation steps included the following: (1) choosing a clinic site, (2) establishing patient access procedures, (3) establishing navigator services, (4) developing subsidy fund use guidelines, and (5) designing recruitment and promotion. Through community-based promotion, 64 men inquired about the program and 26 (41 %) participated. Of those screened, 46 % had abnormal results, and 2 men were diagnosed with prostate cancer. Here, we describe a unique demonstration project to implement a comprehensive prostate cancer risk assessment program in an underserved Black community and describe successes and challenges to inform future efforts to promote access to underserved men.

Compact 151 W green laser with U-type resonator for prostate surgery

NASA Astrophysics Data System (ADS)

Bazyar, Hossein; Aghaie, Mohammad; Daemi, Mohammad Hossein; Bagherzadeh, Seyed Morteza

2013-04-01

We analyzed, designed and fabricated a U-type resonator for intra-cavity frequency doubling of a diode-side-pumped Q-switched Nd:YAG rod laser with high power and high stability for surgery of prostatic tissue. The resonator stability conditions were analyzed graphically in the various configurations for a U-type resonator. We obtained green light at 532 nm using a single KTP crystal, with average output power of 151 W at 10 kHz repetition rate, and with 113 ns pulse duration at 810 W input pump power. We achieved 1064-532 nm conversion efficiency of 75.8%, and pump-to-green optical-optical efficiency of 18.6%. The green power fluctuation was ±1.0% and pointing stability was better than 4 μrad. The green laser output was coupled to a side-firing medical fiber to transfer the laser beam to the prostatic tissue.

Acute inflammatory proteins constitute the organic matrix of prostatic corpora amylacea and calculi in men with prostate cancer

PubMed Central

Sfanos, Karen S.; Wilson, Brice A.; De Marzo, Angelo M.; Isaacs, William B.

2009-01-01

Corpora amylacea (CA) are a frequent microscopic finding in radical prostatectomy specimens from men undergoing treatment for prostate cancer. Although often observed histologically to be associated with inflammation, the contribution of CA to prostatitis-related symptoms of unknown etiology or to prostate carcinogenesis remains unclear. Prostatic calculi (PC), which potentially represent calcified forms of CA, are less common but can cause urological disease including urinary retention and prostatitis. We conducted a comprehensive compositional analysis of CA/PC to gain insight into their biogenesis. Infrared spectroscopy analysis of calculi collected from 23 patients confirmed a prevalence of calcium phosphate in the form of hydroxyapatite. This result sets PC apart from most urinary stones, which largely are composed of calcium oxalate. Tandem mass spectrometry-based proteomic analysis of CA/PC revealed that lactoferrin is the predominant protein component, a result that was confirmed by Western blot analysis. Other proteins identified, including calprotectin, myeloperoxidase, and α-defensins, are proteins contained in neutrophil granules. Immunohistochemistry (IHC) suggested the source of lactoferrin to be prostate-infiltrating neutrophils as well as inflamed prostate epithelium; however, IHC for calprotectin suggested prostate-infiltrating neutrophils as a major source of the protein, because it was absent from other prostate compartments. This study represents a definitive analysis of the protein composition of prostatic CA and calculi and suggests that acute inflammation has a role in their biogenesis—an intriguing finding, given the prevalence of CA in prostatectomy specimens and the hypothesized role for inflammation in prostate carcinogenesis. PMID:19202053

Development of cell-penetrating bispecific antibodies targeting the N-terminal domain of androgen receptor for prostate cancer therapy.

PubMed

Goicochea, Nancy L; Garnovskaya, Maria; Blanton, Mary G; Chan, Grace; Weisbart, Richard; Lilly, Michael B

2017-12-01

Castration-resistant prostate cancer cells exhibit continued androgen receptor signaling in spite of low levels of ligand. Current therapies to block androgen receptor signaling act by inhibiting ligand production or binding. We developed bispecific antibodies capable of penetrating cells and binding androgen receptor outside of the ligand-binding domain. Half of the bispecific antibody molecule consists of a single-chain variable fragment of 3E10, an anti-DNA antibody that enters cells. The other half is a single-chain variable fragment version of AR441, an anti-AR antibody. The resulting 3E10-AR441 bispecific antibody enters human LNCaP prostate cells and accumulates in the nucleus. The antibody binds to wild-type, mutant and splice variant androgen receptor. Binding affinity of 3E10-AR441 to androgen receptor (284 nM) was lower than that of the parental AR441 mAb (4.6 nM), but could be improved (45 nM) through alternative placement of the affinity tags, and ordering of the VH and VK domains. The 3E10-AR441 bispecific antibody blocked genomic signaling by wild-type or splice variant androgen receptor in LNCaP cells. It also blocked non-genomic signaling by the wild-type receptor. Furthermore, bispecific antibody inhibited the growth of C4-2 prostate cancer cells under androgen-stimulated conditions. The 3E10-AR441 biAb can enter prostate cancer cells and inhibits androgen receptor function in a ligand-independent manner. It may be an attractive prototype agent for prostate cancer therapy. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Relation between histological prostatitis and lower urinary tract symptoms and erectile function.

PubMed

Mizuno, Taiki; Hiramatsu, Ippei; Aoki, Yusuke; Shimoyama, Hirofumi; Nozaki, Taiji; Shirai, Masato; Lu, Yan; Horie, Shigeo; Tsujimura, Akira

2017-09-01

Chronic prostatitis (CP) significantly worsens a patient's quality of life (QOL), but its etiology is heterogeneous. Although the inflammatory process must be associated with CP symptoms, not all patients with benign prostatic hyperplasia and histological prostatitis complain of CP symptoms. The relation between the severity of histological inflammation and lower urinary tract symptoms (LUTS) and erectile function is not fully understood. This study comprised 26 men with suspected prostate cancer but with no malignant lesion by pathological examination of prostate biopsy specimens. LUTS were assessed by several questionnaires including the International Prostate Symptom Score (IPSS), QOL index, Overactive Bladder Symptom Score (OABSS), and the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI), and erectile function was assessed by the Sexual Health Inventory for Men. Prostate volume (PV) measured by transabdominal ultrasound, maximum flow rate by uroflowmetry, and serum concentration of prostate-specific antigen were also evaluated. All data collections were performed before prostate biopsy. Histological prostatitis was assessed by immunohistochemical staining with anti-CD45 antibody as the Quick score. The relation between the Quick score and several factors was assessed by Pearson correlation coefficient and a multivariate linear regression model after adjustment for PV. The Pearson correlation coefficient showed a correlation between the Quick score and several factors including PV, IPSS, QOL index, OABSS, and NIH-CPSI. A multivariate linear regression model after adjustment for PV showed only the NIH-CPSI to be associated with the Quick score. The relation between the Quick score and each domain score of the NIH-CPSI showed only the subscore of urinary symptoms to be an associated factor. We found a correlation only between histological prostatitis and LUTS, but not erectile dysfunction. Especially, the subscore of urinary symptoms (residual feeling and urinary frequency) was associated with histological prostatitis.

Evaluation of the Prostate Cancer Prevention Trial Risk Calculator in a High-Risk Screening Population

PubMed Central

Kaplan, David J.; Boorjian, Stephen A.; Ruth, Karen; Egleston, Brian L.; Chen, David Y.T.; Viterbo, Rosalia; Uzzo, Robert G.; Buyyounouski, Mark K.; Raysor, Susan; Giri, Veda N.

2009-01-01

Introduction Clinical factors in addition to PSA have been evaluated to improve risk assessment for prostate cancer. The Prostate Cancer Prevention Trial (PCPT) risk calculator provides an assessment of prostate cancer risk based on age, PSA, race, prior biopsy, and family history. This study evaluated the risk calculator in a screening cohort of young, racially diverse, high-risk men with a low baseline PSA enrolled in the Prostate Cancer Risk Assessment Program. Patients and Methods Eligibility for PRAP include men ages 35-69 who are African-American, have a family history of prostate cancer, or have a known BRCA1/2 mutation. PCPT risk scores were determined for PRAP participants, and were compared to observed prostate cancer rates. Results 624 participants were evaluated, including 382 (61.2%) African-American men and 375 (60%) men with a family history of prostate cancer. Median age was 49.0 years (range 34.0-69.0), and median PSA was 0.9 (range 0.1-27.2). PCPT risk score correlated with prostate cancer diagnosis, as the median baseline risk score in patients diagnosed with prostate cancer was 31.3%, versus 14.2% in patients not diagnosed with prostate cancer (p<0.0001). The PCPT calculator similarly stratified the risk of diagnosis of Gleason score ≥7 disease, as the median risk score was 36.2% in patients diagnosed with Gleason ≥7 prostate cancer versus 15.2% in all other participants (p<0.0001). Conclusion PCPT risk calculator score was found to stratify prostate cancer risk in a cohort of young, primarily African-American men with a low baseline PSA. These results support further evaluation of this predictive tool for prostate cancer risk assessment in high-risk men. PMID:19709072

Insufficient Sleep and Risk of Prostate Cancer in a Large Swedish Cohort.

PubMed

Markt, Sarah C; Grotta, Alessandra; Nyren, Olof; Adami, Hans-Olov; Mucci, Lorelei A; Valdimarsdottir, Unnur A; Stattin, Pär; Bellocco, Rino; Lagerros, Ylva Trolle

2015-09-01

There are some data to suggest that insufficient sleep, including short sleep duration and sleep disruption, may be associated with an increased risk of cancer. We investigated the association between sleep duration and sleep disruption and risk of prostate cancer. Prospective cohort study. Sweden. A total of 14,041 men in the Swedish National March Cohort. None. Habitual sleep duration and sleep disruption were self-reported in 1997. Prostate cancer diagnoses, including lethal (metastases at diagnosis or death from prostate cancer) and advanced (stage T4, N1, or M1 at diagnosis or death from prostate cancer), were determined from linkage to nationwide cancer registries through 2010. We conducted Cox proportional hazards regression adjusted for potential confounding variables. During 13 years of follow-up, we identified 785 cases of incident prostate cancer, including 118 lethal and 127 advanced cases. Four percent of men reported sleeping 5 h or less a night, and 2% reported sleeping 9 h or more per night. We found no association between sleep duration and risk of prostate cancer overall or for advanced/lethal disease. We also did not find an association between prostate cancer and sleep disruption, as defined by difficulty falling asleep, difficulty maintaining sleep, sleep quality, and restorative power of sleep. In this large prospective study from Sweden, we found no association between habitual sleep duration or sleep disruption and risk of prostate cancer. © 2015 Associated Professional Sleep Societies, LLC.

Genetic Association Study of Ancestry-Matched African American Prostate Cancer Cases and Control

DTIC Science & Technology

2009-04-01

TO THE ABOVE ADDRESS. 1. REPORT DATE 1 April 2009 2 . REPORT TYPE Final 3. DATES COVERED 1 April 2008 – 31 March 2009 4. TITLE AND SUBTITLE...matching, we have identified and confirmed several prostate cancer susceptibility loci in this study population, on chromosomes 2 , 8 and 17. These and...prostate cancer susceptibility loci in these studies, on chromosomes 2 , 8, and 17. These and other ongoing studies will provide unprecedented insight

Beta Catenin in Prostate Cancer Apoptosis

DTIC Science & Technology

2014-04-01

indicate that, Glycogen Synthase Kinase 3β (GSK3β) might be a key player in mediating this. GSK3β, a multifunctional serine/ threonine kinase regulates...for TRAIL-TZD-induced apoptosis in prostate cancer cells. AMPK is a family of serine/ threonine protein kinase and is highly conserved from yeast to...metabolic syndrome and Type 2 diabetes . We used C42-DN (stably overexpressing AMPK α1-dominant negative) and C42-EV (empty vector) prostate cancer cell

New Players for Advanced Prostate Cancer and the Rationalisation of Insulin-Sensitising Medication

PubMed Central

Gunter, Jennifer H.; Sarkar, Phoebe L.; Lubik, Amy A.; Nelson, Colleen C.

2013-01-01

Obesity and type 2 diabetes are recognised risk factors for the development of some cancers and, increasingly, predict more aggressive disease, treatment failure, and cancer-specific mortality. Many factors may contribute to this clinical observation. Hyperinsulinaemia, dyslipidaemia, hypoxia, ER stress, and inflammation associated with expanded adipose tissue are thought to be among the main culprits driving malignant growth and cancer advancement. This observation has led to the proposal of the potential utility of “old players” for the treatment of type 2 diabetes and metabolic syndrome as new cancer adjuvant therapeutics. Androgen-regulated pathways drive proliferation, differentiation, and survival of benign and malignant prostate tissue. Androgen deprivation therapy (ADT) exploits this dependence to systemically treat advanced prostate cancer resulting in anticancer response and improvement of cancer symptoms. However, the initial therapeutic response from ADT eventually progresses to castrate resistant prostate cancer (CRPC) which is currently incurable. ADT rapidly induces hyperinsulinaemia which is associated with more rapid treatment failure. We discuss current observations of cancer in the context of obesity, diabetes, and insulin-lowering medication. We provide an update on current treatments for advanced prostate cancer and discuss whether metabolic dysfunction, developed during ADT, provides a unique therapeutic window for rapid translation of insulin-sensitising medication as combination therapy with antiandrogen targeting agents for the management of advanced prostate cancer. PMID:23573093

Differential regulation of insulin-like growth factor-I receptor gene expression by wild type and mutant androgen receptor in prostate cancer cells.

PubMed

Schayek, Hagit; Seti, Hila; Greenberg, Norman M; Sun, Shihua; Werner, Haim; Plymate, Stephen R

2010-07-29

The progression of prostate cancer from an organ-confined, androgen-sensitive disease to a metastatic one is associated with dysregulation of androgen receptor (AR)-regulated target genes and with a decrease in insulin-like growth factor-I receptor (IGF-IR) expression. To investigate the differential effects of wild type (wt) and mutant AR on IGF-IR levels we employed a series of isogenic prostate-derived cell lines and human xenografts. We show that basal and phosphorylated IGF-IR levels progressively decreased as prostate cancer cells became more tumorigenic and metastatic. In addition, we show that wt, but not mutant, AR along with dihydrotestosterone treatment increased IGF-IR promoter activity and endogenous IGF-IR levels. ChIP analysis show enhanced AR binding to the IGF-IR promoter in AR-overexpressing cells. Finally, wt AR-overexpressing cells display an enhanced proliferation rate. In summary, we provide evidence that activated wt AR enhances IGF-IR transcription in prostate cancer cells via a mechanism that involves AR binding to the IGF-IR promoter. AR mutations alter the ability of the mutated protein to regulate IGF-IR expression. Our results suggest that prostate cancer progression is associated with a decrease in IGF-IR expression that could be the result of impaired ability of AR to stimulate IGF-IR gene expression. 2010 Elsevier Ireland Ltd. All rights reserved.

Differential regulation of insulin-like growth factor-I receptor gene expression by wild type and mutant androgen receptor in prostate cancer cells

PubMed Central

Schayek, Hagit; Seti, Hila; Greenberg, Norman M.; Sun, Shihua; Werner, Haim; Plymate, Stephen R.

2010-01-01

The progression of prostate cancer from an organ-confined, androgen-sensitive disease to a metastatic one is associated with dysregulation of androgen receptor (AR)-regulated target genes and with a decrease in insulin-like growth factor-I receptor (IGF-IR) expression. To investigate the differential effects of wild type (wt) and mutant AR on IGF-IR levels we employed a series of isogenic prostate-derived cell lines and human xenografts. We show that basal and phosphorylated IGF-IR levels progressively decreased as prostate cancer cells became more tumorigenic and metastatic. In addition, we show that wt, but not mutant, AR along with dihydrotestosterone treatment increased IGF-IR promoter activity and endogenous IGF-IR levels. ChIP analysis show enhanced AR binding to the IGF-IR promoter in AR-overexpressing cells. Finally, wt AR-overexpressing cells display an enhanced proliferation rate. In summary, we provide evidence that activated wt AR enhances IGF-IR transcription in prostate cancer cells via a mechanism that involves AR binding to the IGF-IR promoter. AR mutations alter the ability of the mutated protein to regulate IGF-IR expression. Our results suggest that prostate cancer progression is associated with a decrease in IGF-IR expression that could be the result of impaired ability of AR to stimulate IGF-IR gene expression. PMID:20417685

How does health literacy affect quality of life among men with newly diagnosed clinically localized prostate cancer? Findings from the North Carolina-Louisiana Prostate Cancer Project (PCaP).

PubMed

Song, Lixin; Mishel, Merle; Bensen, Jeannette T; Chen, Ronald C; Knafl, George J; Blackard, Bonny; Farnan, Laura; Fontham, Elizabeth; Su, L Joseph; Brennan, Christine S; Mohler, James L; Godley, Paul A

2012-08-01

Health literacy deficits affect half of the US overall patient population, especially the elderly, and are linked to poor health outcomes among noncancer patients. Yet little is known about how health literacy affects cancer populations. The authors examined the relation between health-related quality of life (HRQOL) and health literacy among men with prostate cancer. Data analysis included 1581 men with newly diagnosed clinically localized prostate cancer from a population-based study, the North Carolina-Louisiana Prostate Cancer Project (PCaP). Participants completed assessment of health literacy using Rapid Estimate of Adult Literacy in Medicine (REALM) and HRQOL using the Short Form-12 General Health Survey (SF12). Bivariate and multivariate regression was used to determine the potential association between REALM and HRQOL, while controlling for sociodemographic and illness-related variables. Higher health literacy level was significantly associated with better mental well-being (SF12-Mental Component Summary [MCS]; P < .001) and physical well-being (SF12-Physical Component Summary [PCS]; P < .001) in bivariate analyses. After controlling for sociodemographic (age, marital status, race, income, and education) and illness-related factors (types of cancer treatment, tumor aggressiveness, and comorbidities), health literacy remained significantly associated with SF12-MCS scores (P < .05) but not with SF12-PCS scores. Among patients with newly diagnosed localized prostate cancer, those with low health literacy levels were more vulnerable to mental distress than those with higher health literacy levels, but physical well-being was no different. These findings suggest that health literacy may be important in patients managing prostate cancer and the effects of treatment, and provide the hypothesis that supportive interventions targeting patients with lower health literacy may improve their HRQOL. Copyright © 2011 American Cancer Society.

Targeted delivery of cisplatin to prostate cancer cells by aptamer functionalized Pt(IV) prodrug-PLGA-PEG nanoparticles.

PubMed

Dhar, Shanta; Gu, Frank X; Langer, Robert; Farokhzad, Omid C; Lippard, Stephen J

2008-11-11

Cisplatin is used to treat a variety of tumors, but dose limiting toxicities or intrinsic and acquired resistance limit its application in many types of cancer including prostate. We report a unique strategy to deliver cisplatin to prostate cancer cells by constructing Pt(IV)-encapsulated prostate-specific membrane antigen (PSMA) targeted nanoparticles (NPs) of poly(D,L-lactic-co-glycolic acid) (PLGA)-poly(ethylene glycol) (PEG)-functionalized controlled release polymers. By using PLGA-b-PEG nanoparticles with PSMA targeting aptamers (Apt) on the surface as a vehicle for the platinum(IV) compound c,t,c-[Pt(NH(3))(2)(O(2)CCH(2)CH(2)CH(2)CH(2)CH(3))(2)Cl(2)] (1), a lethal dose of cisplatin was delivered specifically to prostate cancer cells. PSMA aptamer targeted delivery of Pt(IV) cargos to PSMA(+) LNCaP prostate cancer cells by endocytosis of the nanoparticle vehicles was demonstrated using fluorescence microscopy by colocalization of green fluorescent labeled cholesterol-encapsulated NPs and early endosome marker EEA-1. The choice of linear hexyl chains in 1 was the result of a systematic study to optimize encapsulation and controlled release from the polymer without compromising either feature. Release of cisplatin from the polymeric nanoparticles after reduction of 1 and formation of cisplatin 1,2-intrastrand d(GpG) cross-links on nuclear DNA was confirmed by using a monoclonal antibody for the adduct. A comparison between the cytotoxic activities of Pt(IV)-encapsulated PLGA-b-PEG NPs with the PSMA aptamer on the surface (Pt-NP-Apt), cisplatin, and the nontargeted Pt(IV)-encapsulated NPs (Pt-NP) against human prostate PSMA-overexpressing LNCaP and PSMA(-) PC3 cancer cells revealed significant differences. The effectiveness of PSMA targeted Pt-NP-Apt nanoparticles against the PSMA(+) LNCaP cells is approximately an order of magnitude greater than that of free cisplatin.

Mortality results from a randomized prostate-cancer screening trial.

PubMed

Andriole, Gerald L; Crawford, E David; Grubb, Robert L; Buys, Saundra S; Chia, David; Church, Timothy R; Fouad, Mona N; Gelmann, Edward P; Kvale, Paul A; Reding, Douglas J; Weissfeld, Joel L; Yokochi, Lance A; O'Brien, Barbara; Clapp, Jonathan D; Rathmell, Joshua M; Riley, Thomas L; Hayes, Richard B; Kramer, Barnett S; Izmirlian, Grant; Miller, Anthony B; Pinsky, Paul F; Prorok, Philip C; Gohagan, John K; Berg, Christine D

2009-03-26

The effect of screening with prostate-specific-antigen (PSA) testing and digital rectal examination on the rate of death from prostate cancer is unknown. This is the first report from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial on prostate-cancer mortality. From 1993 through 2001, we randomly assigned 76,693 men at 10 U.S. study centers to receive either annual screening (38,343 subjects) or usual care as the control (38,350 subjects). Men in the screening group were offered annual PSA testing for 6 years and digital rectal examination for 4 years. The subjects and health care providers received the results and decided on the type of follow-up evaluation. Usual care sometimes included screening, as some organizations have recommended. The numbers of all cancers and deaths and causes of death were ascertained. In the screening group, rates of compliance were 85% for PSA testing and 86% for digital rectal examination. Rates of screening in the control group increased from 40% in the first year to 52% in the sixth year for PSA testing and ranged from 41 to 46% for digital rectal examination. After 7 years of follow-up, the incidence of prostate cancer per 10,000 person-years was 116 (2820 cancers) in the screening group and 95 (2322 cancers) in the control group (rate ratio, 1.22; 95% confidence interval [CI], 1.16 to 1.29). The incidence of death per 10,000 person-years was 2.0 (50 deaths) in the screening group and 1.7 (44 deaths) in the control group (rate ratio, 1.13; 95% CI, 0.75 to 1.70). The data at 10 years were 67% complete and consistent with these overall findings. After 7 to 10 years of follow-up, the rate of death from prostate cancer was very low and did not differ significantly between the two study groups. (ClinicalTrials.gov number, NCT00002540.) 2009 Massachusetts Medical Society

Percent free prostate-specific antigen for prostate cancer diagnosis in Chinese men with a PSA of 4.0-10.0 ng/mL: Results from the Chinese Prostate Cancer Consortium.

PubMed

Chen, Rui; Xie, Liping; Cai, Xiaobing; Huang, Yiran; Zhou, Liqun; Ma, Lulin; Gao, Xu; Xu, Chuanliang; Ren, Shancheng; Shao, Pengfei; Xu, Danfeng; Xu, Kexin; Ye, Zhangqun; Liu, Chunxiao; Ye, Dingwei; Lu, Li; Fu, Qiang; Hou, Jianquan; Yuan, Jianlin; He, Dalin; Zhou, Tie; Wang, Fubo; He, Biming; Sun, Yinghao

2015-04-01

To test the diagnostic performance of percent free prostate-specific antigen (%fPSA) in predicting any prostate cancer (PCa) and high-grade prostate cancer (HGPCa) in a retrospective multi-center biopsy cohort with a PSA level of 4.0-10.0 ng/mL in China. Consecutive patients with a PSA of 4.0-10.0 ng/mL who underwent transrectal ultrasound-guided biopsy were enrolled at 16 Chinese medical centers from January 1st, 2010 to December 31st, 2013. Total and free serum PSA determinations were performed using three types of electro-chemiluminescence immunoassays recalibrated to the World Health Organization (WHO) standard. The diagnostic accuracy of PSA, %fPSA, and %fPSA in combination with PSA (%fPSA + PSA) was determined using the area under the receiver operating characteristic (ROC) curve (AUC). A total of 2310 consecutive men with PSA levels between 4.0 and 10.0 ng/mL were included, and the detection rate of PCa was 25.1%. The AUC of %fPSA and %fPSA + PSA in predicting any PCa was superior to PSA alone in men aged ≥60 years (0.623 vs. 0.534, p  < 0.0001) but not in men aged 40-59 years (0.517 vs. 0.518, p  = 0.939). Similar result was yield in predicting HGPCa. In a clinical setting of Chinese men with 4.0-10.0 ng/mL PSA undergoing initial prostate biopsy, adding %fPSA to PSA can moderately improve the diagnostic accuracy for any PCa and HGPCa compared with PSA alone in patients ≥60 but not in patients aged 40-59 years.

Late-onset granulomatous prostatitis following intravesical bacille Calmette-Guerin therapy: case report.

PubMed

Castillo Cádiz, Octavio; Villasenín Parrado, Lorena; Borgna Christie, Vincenzo; Gallegos Méndez, Iván; Martínez Corta, Virginia

2016-06-20

Bacille Calmette-Guerin intravesical treatment is the most effective treatment for reducing the recurrence of non-muscle-invasive urothelial carcinomas. This treatment can sometimes have side effects and serious complications. Granulomatous prostatitis is a common histological finding but it rarely has a clinical presentation. We report a case of a 75-year-old, type 2 diabetic, male patient who was diagnosed with urothelial in situ carcinoma, for which he began treatment with Bacille Calmette-Guerin instillations. Five years later the patient presented nocturia, pollakiuria, severe urgency, and intense and recurrent perineal pain associated with marked elevation of prostatic specific antigen. A prostatic biopsy was performed that showed a moderate to severe granulomatous prostatitis related to bacille Calmette-Guerin. The patient received full antituberculosis combination drugs with a favorable clinical response.

Ornithine Decarboxylase Activity Is Required for Prostatic Budding in the Developing Mouse Prostate

PubMed Central

Gamat, Melissa; Malinowski, Rita L.; Parkhurst, Linnea J.; Steinke, Laura M.; Marker, Paul C.

2015-01-01

The prostate is a male accessory sex gland that produces secretions in seminal fluid to facilitate fertilization. Prostate secretory function is dependent on androgens, although the mechanism by which androgens exert their effects is still unclear. Polyamines are small cationic molecules that play pivotal roles in DNA transcription, translation and gene regulation. The rate-limiting enzyme in polyamine biosynthesis is ornithine decarboxylase, which is encoded by the gene Odc1. Ornithine decarboxylase mRNA decreases in the prostate upon castration and increases upon administration of androgens. Furthermore, testosterone administered to castrated male mice restores prostate secretory activity, whereas administering testosterone and the ornithine decarboxylase inhibitor D,L-α-difluromethylornithine (DFMO) to castrated males does not restore prostate secretory activity, suggesting that polyamines are required for androgens to exert their effects. To date, no one has examined polyamines in prostate development, which is also androgen dependent. In this study, we showed that ornithine decarboxylase protein was expressed in the epithelium of the ventral, dorsolateral and anterior lobes of the adult mouse prostate. Ornithine decarboxylase protein was also expressed in the urogenital sinus (UGS) epithelium of the male and female embryo prior to prostate development, and expression continued in prostatic epithelial buds as they emerged from the UGS. Inhibiting ornithine decarboxylase using DFMO in UGS organ culture blocked the induction of prostatic buds by androgens, and significantly decreased expression of key prostate transcription factor, Nkx3.1, by androgens. DFMO also significantly decreased the expression of developmental regulatory gene Notch1. Other genes implicated in prostatic development including Sox9, Wif1 and Srd5a2 were unaffected by DFMO. Together these results indicate that Odc1 and polyamines are required for androgens to exert their effect in mediating prostatic bud induction, and are required for the expression of a subset of prostatic developmental regulatory genes including Notch1 and Nkx3.1. PMID:26426536

Reduction of prostate intrafraction motion using gas-release rectal balloons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Su Zhong; Zhao Tianyu; Li Zuofeng

2012-10-15

Purpose: To analyze prostate intrafraction motion using both non-gas-release (NGR) and gas-release (GR) rectal balloons and to evaluate the ability of GR rectal balloons to reduce prostate intrafraction motion. Methods: Twenty-nine patients with NGR rectal balloons and 29 patients with GR balloons were randomly selected from prostate patients treated with proton therapy at University of Florida Proton Therapy Institute (Jacksonville, FL). Their pretreatment and post-treatment orthogonal radiographs were analyzed, and both pretreatment setup residual error and intrafraction-motion data were obtained. Population histograms of intrafraction motion were plotted for both types of balloons. Population planning target-volume (PTV) margins were calculated withmore » the van Herk formula of 2.5{Sigma}+ 0.7{sigma} to account for setup residual errors and intrafraction motion errors. Results: Pretreatment and post-treatment radiographs indicated that the use of gas-release rectal balloons reduced prostate intrafraction motion along superior-inferior (SI) and anterior-posterior (AP) directions. Similar patient setup residual errors were exhibited for both types of balloons. Gas-release rectal balloons resulted in PTV margin reductions from 3.9 to 2.8 mm in the SI direction, 3.1 to 1.8 mm in the AP direction, and an increase from 1.9 to 2.1 mm in the left-right direction. Conclusions: Prostate intrafraction motion is an important uncertainty source in radiotherapy after image-guided patient setup with online corrections. Compared to non-gas-release rectal balloons, gas-release balloons can reduce prostate intrafraction motion in the SI and AP directions caused by gas buildup.« less

Benign Prostatic Hyperplasia and the Risk of Prostate Cancer and Bladder Cancer

PubMed Central

Dai, Xiaoyu; Fang, Xiangming; Ma, Ying; Xianyu, Jianbo

2016-01-01

Abstract Benign prostatic hyperplasia (BPH) has been suggested to be a risk factor for certain urologic cancers, but the current evidence is inconsistent. The aim of this study was to investigate the association between BPH and urologic cancers. MEDLINE, EMBASE, Cochrane Library, and Web of Science were searched for potential eligible studies. We included case-control studies or cohort studies, which evaluated the association between BPH and urologic cancers (including prostate cancer, bladder cancer, kidney cancer, testicular cancer, or penile cancer). Overall effect estimates were calculated using the DerSimonian–Laird method for a random-effects model. Summary effect-size was calculated as risk ratio (RR), together with the 95% confidence interval (CI). This systematic review included 16 case-control studies and 10 cohort studies evaluating the association of BPH and prostate or bladder cancer; we did not identify any study about other urologic cancers. Meta-analyses demonstrated that BPH was associated with an increased incidence of prostate cancer (case-control study: RR = 3.93, 95% CI = 2.18–7.08; cohort-study: RR = 1.41, 95% CI = 1.00–1.99) and bladder cancer (case-control study: RR = 2.50, 95% CI = 1.63–3.84; cohort-study: RR = 1.58, 95% CI = 1.28–1.95). Subgroup analysis by ethnicity suggested that the association between BPH and prostate cancer was much stronger in Asians (RR = 6.09, 95% CI = 2.96–12.54) than in Caucasians (RR = 1.54, 95% CI = 1.19–2.01). Egger's tests indicated low risk of publication bias (prostate cancer: P = 0.11; bladder cancer: P = 0.95). BPH is associated with an increased risk of prostate cancer and bladder cancer. The risk of prostate cancer is particularly high in Asian BPH patients. Given the limitations of included studies, additional prospective studies with strict design are needed to confirm our findings. PMID:27149447

Strong expression of the neuronal transcription factor FOXP2 is linked to an increased risk of early PSA recurrence in ERG fusion-negative cancers.

PubMed

Stumm, Laura; Burkhardt, Lia; Steurer, Stefan; Simon, Ronald; Adam, Meike; Becker, Andreas; Sauter, Guido; Minner, Sarah; Schlomm, Thorsten; Sirma, Hüseyin; Michl, Uwe

2013-07-01

Transcription factors of the forkhead box P (FOXP1-4) family have been implicated in various human cancer types before. The relevance and role of neuronal transcription factor FOXP2 in prostate cancer is unknown. A tissue microarray containing samples from more than 11 000 prostate cancers from radical prostatectomy specimens with clinical follow-up data was analysed for FOXP2 expression by immunohistochemistry. FOXP2 data were also compared with pre-existing ERG fusion (by fluorescence in situ hybridisation and immunohistochemistry) and cell proliferation (Ki67 labelling index) data. There was a moderate to strong FOXP2 protein expression in basal and secretory cells of normal prostatic glands. As compared with normal cells, FOXP2 expression was lost or reduced in 25% of cancers. Strong FOXP2 expression was linked to advanced tumour stage, high Gleason score, presence of lymph node metastases and early tumour recurrence (p<0.0001; each) in ERG fusion-negative, but not in ERG fusion-positive cancers. High FOXP2 expression was linked to high Ki67 labelling index (p<0.0001) in all cancers irrespective of ERG fusion status. These data demonstrate that similar high FOXP2 protein levels as in normal prostate epithelium exert a 'paradoxical' oncogenic role in 'non fusion-type' prostate cancer. It may be speculated that interaction of FOXP2 with members of pathways that are specifically activated in 'non fusion-type' cancers may be responsible for this phenomenon.

Recruitment of African Americans into prostate cancer screening.

PubMed

Weinrich, S P; Boyd, M D; Bradford, D; Mossa, M S; Weinrich, M

1998-01-01

Both incidence and mortality rates for prostate cancer are significantly higher in African American men than in white men. This report identifies community sites for the optimal recruitment of African American men into prostate cancer screening. A descriptive study was conducted, providing an educational program to 1369 African American men, 1264 of whom completed a survey on demographic data, prostate cancer knowledge, and prostate cancer screening history. The programs were offered at six different types of community sites, including various work sites, churches, housing projects, National Association for Advancement of Colored Persons (NAACP) sites, barber shops, and a state fairground. Free prostate cancer screening was offered to all participants. The advertised mass screening site (state fairground), the most common method used nationally to recruit African American men for cancer screening, was the least effective site, with only 16 men completing the survey. Of the 1264 men completing the survey at all community sites, 597 men (47%) did so at work sites and 438 (35%) did so at churches. Per site, the largest percentage of men who had never been screened was at work sites (n = 276, 46%) and NAACP sites (n = 22, 33.8%). The highest percentage of men who obtained free screening were at the state fairground (14 of 16), churches (256 of 438), and work sites (336 of 597). The most prostate cancers were detected at the housing projects, where 3 of 38 (7.9%) men who were screened received diagnoses of prostate cancer. To reduce prostate mortality rates in African American men, healthcare providers need to make a concerted effort to increase prostate cancer education and screening in this population. To be effective, recruitment of African American men must move from a provider/health site orientation to a consumer/community orientation. These findings indicate that recruitment strategies are more successful if efforts are based in the community or where a large number of African American men live and/or work. Because a history of screening has been shown to be a predictor for current participation, programs need to target men who have not had previous screening ever or within the last year. In addition, the large percentage of men recruited at work sites who had not been screened previously indicates an opportunity for collaboration with healthcare professionals in employee health programs. Efforts to increase participation in prostate cancer screening will be enhanced significantly by eliciting the active involvement of community leaders.

Cascaded discrimination of normal, abnormal, and confounder classes in histopathology: Gleason grading of prostate cancer

PubMed Central

2012-01-01

Background Automated classification of histopathology involves identification of multiple classes, including benign, cancerous, and confounder categories. The confounder tissue classes can often mimic and share attributes with both the diseased and normal tissue classes, and can be particularly difficult to identify, both manually and by automated classifiers. In the case of prostate cancer, they may be several confounding tissue types present in a biopsy sample, posing as major sources of diagnostic error for pathologists. Two common multi-class approaches are one-shot classification (OSC), where all classes are identified simultaneously, and one-versus-all (OVA), where a “target” class is distinguished from all “non-target” classes. OSC is typically unable to handle discrimination of classes of varying similarity (e.g. with images of prostate atrophy and high grade cancer), while OVA forces several heterogeneous classes into a single “non-target” class. In this work, we present a cascaded (CAS) approach to classifying prostate biopsy tissue samples, where images from different classes are grouped to maximize intra-group homogeneity while maximizing inter-group heterogeneity. Results We apply the CAS approach to categorize 2000 tissue samples taken from 214 patient studies into seven classes: epithelium, stroma, atrophy, prostatic intraepithelial neoplasia (PIN), and prostate cancer Gleason grades 3, 4, and 5. A series of increasingly granular binary classifiers are used to split the different tissue classes until the images have been categorized into a single unique class. Our automatically-extracted image feature set includes architectural features based on location of the nuclei within the tissue sample as well as texture features extracted on a per-pixel level. The CAS strategy yields a positive predictive value (PPV) of 0.86 in classifying the 2000 tissue images into one of 7 classes, compared with the OVA (0.77 PPV) and OSC approaches (0.76 PPV). Conclusions Use of the CAS strategy increases the PPV for a multi-category classification system over two common alternative strategies. In classification problems such as histopathology, where multiple class groups exist with varying degrees of heterogeneity, the CAS system can intelligently assign class labels to objects by performing multiple binary classifications according to domain knowledge. PMID:23110677

Prostate Cancer Pathology Resource Network

DTIC Science & Technology

2012-07-01

microarrays (TMAs), serum, plasma , buffy coat, prostatic fluid, and derived specimens (DNA and RNA); these specimens are linked to clinical and...research community. The specimens in the PCBN include tissues from prostatectomies, serum, plasma , buffy coat, prostatic fluid, derived specimens such...prostatectomy, seminal vesicles), body fluids (serum, plasma , buffy coat, prostatic fluid; most can be matched to tumor and benign tissue), and

Metallothionein - immunohistochemical cancer biomarker: a meta-analysis.

PubMed

Gumulec, Jaromir; Raudenska, Martina; Adam, Vojtech; Kizek, Rene; Masarik, Michal

2014-01-01

Metallothionein (MT) has been extensively investigated as a molecular marker of various types of cancer. In spite of the fact that numerous reviews have been published in this field, no meta-analytical approach has been performed. Therefore, results of to-date immunohistochemistry-based studies were summarized using meta-analysis in this review. Web of science, PubMed, Embase and CENTRAL databases were searched (up to April 30, 2013) and the eligibility of individual studies and heterogeneity among the studies was assessed. Random and fixed effects model meta-analysis was employed depending on the heterogeneity, and publication bias was evaluated using funnel plots and Egger's tests. A total of 77 studies were included with 8,015 tissue samples (4,631 cases and 3,384 controls). A significantly positive association between MT staining and tumors (vs. healthy tissues) was observed in head and neck (odds ratio, OR 9.95; 95% CI 5.82-17.03) and ovarian tumors (OR 7.83; 1.09-56.29), and a negative association was ascertained in liver tumors (OR 0.10; 0.03-0.30). No significant associations were identified in breast, colorectal, prostate, thyroid, stomach, bladder, kidney, gallbladder, and uterine cancers and in melanoma. While no associations were identified between MT and tumor staging, a positive association was identified with the tumor grade (OR 1.58; 1.08-2.30). In particular, strong associations were observed in breast, ovarian, uterine and prostate cancers. Borderline significant association of metastatic status and MT staining were determined (OR 1.59; 1.03-2.46), particularly in esophageal cancer. Additionally, a significant association between the patient prognosis and MT staining was also demonstrated (hazard ratio 2.04; 1.47-2.81). However, a high degree of inconsistence was observed in several tumor types, including colorectal, kidney and prostate cancer. Despite the ambiguity in some tumor types, conclusive results are provided in the tumors of head and neck, ovary and liver and in relation to the tumor grade and patient survival.

Differential expression of immune factor between patients with chronic prostatitis/chronic pelvic pain syndrome and the healthy volunteers.

PubMed

Ye, Chen; Xiao, Guang'an; Xu, Jian; Qin, Shengfei; Luo, Yuhua; Chen, Guanghua; Lai, H Henry; Zhou, Tie

2018-03-01

Immune mechanisms have been hypothesized to contribute to the development of CP/CPPS. In this study, we investigated the differential expression of immune factors between patients with CP/CPPS and healthy volunteers. This study was registered in Australian New Zealand Clinical Trials Registry. Healthy volunteers and patients with CP/CPPS were enrolled in this study. The inclusion criteria for patients were below: (1) aged 18-45 years old; (2) prostatitis-related syndrome longer than 3 months; (3) normal routine urine culture and negative bacterial culture in prostatic fluid. Patients were further classified into two groups: types IIIA and IIIB CP/CPPS according to the results of EPS routine test. Serum immune markers include IgA, IgM, IgG, CD4 + and CD8 + . There are total 23 CP/CPPS patients, including 12 type IIIB and 11 type IIIA. Relatively, there are 26 healthy volunteers. The serum levels of IgG were higher in CP/CPPS patients compared to healthy volunteers (1141.2 ± 204.3 vs 1031.9 ± 173.7 mg/L, p = 0.045), while the serum levels of CD8 + were lower in CP/CPPS patients compared to healthy volunteers (492.8 ± 185.6 vs 640.0 ± 246.8 cells/μL, p = 0.021). Furthermore, serum levels of IgG were higher in patients with IIIA CP/CPPS compared to those with IIIB (1244.3 ± 151.6 vs 1054.3 ± 209.3 mg/L, p = 0.023). Differential levels of IgG and CD8 + between CPPS patients and healthy volunteers suggest a contributing role of immune mechanisms to the development of CP/CPPS; and IgG may play an important role in inflammatory CPPS. Clinical Study registration number ACTRN12613000792729.

Cadaveric and radiologic study of the anatomical variations of the prostatic arteries: A review of the literature and a new classification proposal with application to prostatectomy.

PubMed

Moya, Celia; Cuesta, Julián; Friera, Alfonsina; Gil-Vernet Sedó, Jose María; Valderrama-Canales, Francisco J

2017-01-01

Development of prostatic arterial embolization (PAE) to treat benign prostatic hyperplasia (BPH) has raised interest in the variations of the prostatic arteries (PA). The aim of this study is to identify these vascular variations, to compare them with previous data, and to propose a simple classification. Ten adult male pelvis sides from embalmed cadavers were dissected, ages 69 to 92 years, and 10 PA were examined. In a retrospective analysis of 34 DSA pelvic angiographies on 28 patients aged 50 to 90 years, 48 PA were identified. A total of 58 PA were therefore analyzed. Six types are defined. Type I: PA originates from the anterior division (AD) of the internal iliac artery (IIA), 20.7%; Type II: PA emerges from the obturator artery (OA), 5.2%; type III: PA arises from the gluteal-pudendal trunk (GPT), 27.5%; Type IV: PA originates from the internal pudendal artery (IPA), 29.3%; Type V: PA comes from the middle rectal artery (MRA), 15.5%. Other origins, not observed in our sample but described in the literature, were amalgamated under Type VI. The AD/GPT/IPA stem is the main source of the PA. Analysis of the definitions of IIA branches and the associated terminology is necessary for interpreting the results reported by several authors on different samples, but in general the results fit the meta-analysis well. A new, simple, and complete classification for vascular variations of the PA is proposed. Clin. Anat. 30:71-80, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Multifunctional PSCA Antibody Fragments for PET and Optical Prostate Cancer Imaging

DTIC Science & Technology

2016-10-01

INVESTIGATOR: Anna M. Wu CONTRACTING ORGANIZATION: University of California, Los Angeles Los Angeles, CA 90095-1406 REPORT DATE : October 2016 TYPE OF...control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE October 2016 2. REPORT TYPE Annual 3. DATES COVERED 30 Sep 2015...minibodies and cys-diabodies) can be labeled with radioisotopes for non-invasive PET imaging for use at multiple points in the prostate cancer treatment

Increased frequency and nocturia in a middle aged male may not always be due to benign prostatic hypertrophy: a case report.

PubMed

Gaurav, Kumar; Fitch, Jamie; Panda, Mukta

2009-09-15

Primary signet ring cell carcinoma of urinary bladder is a rare type of bladder tumor and carries a very high mortality rate. It may have a clinical presentation similar to common diseases like benign prostatic hypertrophy and the management options are extremely limited. We report a case of 58-year-old Caucasian male who presented with a 5 month history of increased frequency of urination, nocturia and weight loss without any fever or hematuria. He was found to have an increased creatinine of 2.8 mg/dl and a prostate specific antigen level of 0.18 ng/ml. His azotemia was thought to be secondary to BPH. A Foley catheter was initially placed with a plan for outpatient follow up. On removal of the catheter his problems persisted and he returned to the hospital. Diagnostic work up including abdominal ultrasonography, computed tomography scan, retrograde pyelogram, cystography and cystoscopic biopsies revealed the diagnosis of primary signet ring cell carcinoma of urinary bladder. Although cystectomy was planned, our patient passed away before this could be done.

Increased frequency and nocturia in a middle aged male may not always be due to Benign Prostatic Hypertrophy (BPH): a case report.

PubMed

Gaurav, Kumar; Fitch, Jamie; Panda, Mukta

2009-10-27

Primary signet ring cell carcinoma of urinary bladder is a rare type of bladder tumor and carries a very high mortality rate. It may have a clinical presentation similar to common diseases like Benign Prostatic Hypertrophy (BPH) and the management options are extremely limited. We report a case of 58 year old Caucasian male who presented with a 5 month history of increased frequency of urination, nocturia and weight loss without any fever or hematuria. He was found to have an increased creatinine of 2.8 mg/dl and a prostate specific antigen level of 0.18 ng/ml. His azotemia was thought to be secondary to BPH. A foley catheter was initially placed with a plan for outpatient follow up. On removal of the catheter his problems persisted and he returned to the hospital. Diagnostic work up including abdominal ultrasonography, computed tomography (CT) scan, retrograde pyelogram, cystography and cystoscopic biopsies revealed the diagnosis of primary signet ring cell carcinoma of urinary bladder. Although cystectomy was planned, our patient passed away before this could be done.

Ultrasound detection of prostatic calculi as a parameter to predict the appearance of hematospermia after a prostate biopsy.

PubMed

Dell'Atti, Lucio

2017-01-01

We evaluated the correlation between prostate calculi and hematospermia in patients undergoing prostate biopsy, and its impact on sexual activity of patients. A single-center prospective randomized study of 212 patients referred for transrectal ultrasound-guided prostate biopsy (TRUSBx) was performed. All patients were divided into two groups: Group A (GA), 106 patients with moderate/marked presence of prostatic calculi visualized by TRUS; Group B (GB), 106 patients with absence/scarce of prostatic calcifications. Patients were handed questionnaires to obtain a validated data on the duration and impact of hematospermia on sexual activity. The anxiety scores were recorded using a visual analogue scale. No significant difference was noted between the two groups when comparing age, preoperative PSA level, prostate volume, and biopsy number, except for digital rectal examination (DRE) findings. Post-biopsy results of patients included in GA revealed that the complication of hematospermia was present in 65.1%, while in GB was present in 39.7% (p<0.001). On multivariate analysis for identifying significant preoperative predictors of hematospermia, which included variables of age, PSA, prostate volume, and prostate cancer were not shown to be significant predictors of hematospermia, except DRE and prostate calculi (p<0.001). The mean anxiety score was 3.7±2.8 in GA and 2.3±1.9 in GB, respectively (p<0.001). Prostatic calculi are an independent predictive factor of severe hematospermia after TRUSBx on the basis of multivariate analysis, but don't affect the positive rate of prostate cancer. Patients should be adequately counselled before TRUSBx to avoid undue anxiety and alterations in sexual activity. Copyright® by the International Brazilian Journal of Urology.

SOX4 is essential for prostate tumorigenesis initiated by PTEN ablation | Office of Cancer Genomics

Cancer.gov

Understanding remains incomplete of the mechanisms underlying initiation and progression of prostate cancer, the most commonly diagnosed cancer in American men. The transcription factor SOX4 is overexpressed in many human cancers, including prostate cancer, suggesting it may participate in prostate tumorigenesis. In this study, we investigated this possibility by genetically deleting Sox4 in a mouse model of prostate cancer initiated by loss of the tumor suppressor Pten.

Disparities in staging prostate magnetic resonance imaging utilization for nonmetastatic prostate cancer patients undergoing definitive radiation therapy.

PubMed

Ajayi, Ayobami; Hwang, Wei-Ting; Vapiwala, Neha; Rosen, Mark; Chapman, Christina H; Both, Stefan; Shah, Meera; Wang, Xingmei; Agawu, Atu; Gabriel, Peter; Christodouleas, John; Tochner, Zelig; Deville, Curtiland

2016-01-01

There is growing evidence supporting incorporating multiparametric (mp) magnetic resonance imaging (MRI) scans into risk stratification, active surveillance, and treatment paradigms for prostate cancer. The purpose of our study was to determine whether demographic disparities exist in staging MRI utilization for prostate cancer patients. An institutional database of 705 nonmetastatic prostate cancer patients treated with radiation therapy from 2005 through 2013 was used to identify patients undergoing versus not undergoing pretreatment diagnostic prostate mpMRI. Uni- and multivariable logistic regression evaluated the relationship of clinical and demographic characteristics with MRI utilization. All demographic variables assessed, except the other race category, were significantly associated with MRI utilization (all P < .05), including age (odds ratio [OR], 0.92), black race (OR, 0.51), poverty (OR, 0.53), closer distance to radiation facility (OR, 1.79), and nonprivate primary insurance (OR, 0.57) on univariable analysis, while clinical stage T3 (OR, 3.37) was the only clinical characteristic. On multivariable analysis stratified by D'Amico risk group, age remained significant across all risk groups, whereas the black versus white racial (OR, 0.21; 95% confidence interval, 0.08-0.55) and nonprivate versus private insurance type (OR, 0.37; 95% confidence interval, 0.16-0.86) disparities persisted in the low-risk group. Clinical stage T3 remained associated in the high-risk group. For race specifically, the percentages of whites, blacks, and others undergoing MRI in the overall cohort and by risk group were, respectively: overall, 80% (343/427), 68% (156/231), and 85% (40/47); low risk, 86%, 56%, and 63%; intermediate risk, 79%, 72%, and 95%; and high risk, 72%, 72%, and 100%. In this urban, academic center cohort, older patients across all risk groups and black or nonprivate insurance patients in the low risk group were less likely to undergo staging prostate MRI scans. Further research should investigate these differences to ensure equitable utilization across all demographic groups considering the burden of prostate cancer disparities.

Distinct function of estrogen receptor α in smooth muscle and fibroblast cells in prostate development.

PubMed

Vitkus, Spencer; Yeh, Chiuan-Ren; Lin, Hsiu-Hsia; Hsu, Iawen; Yu, Jiangzhou; Chen, Ming; Yeh, Shuyuan

2013-01-01

Estrogen signaling, through estrogen receptor (ER)α, has been shown to cause hypertrophy in the prostate. Our recent report has shown that epithelial ERα knockout (KO) will not affect the normal prostate development or homeostasis. However, it remains unclear whether ERα in different types of stromal cells has distinct roles in prostate development. This study proposed to elucidate how KO of ERα in the stromal smooth muscle or fibroblast cells may interrupt cross talk between prostate stromal and epithelial cells. Smooth muscle ERαKO (smERαKO) mice showed decreased glandular infolding with the proximal area exhibiting a significant decrease. Fibroblast ERαKO mouse prostates did not exhibit this phenotype but showed a decrease in the number of ductal tips. Additionally, the amount of collagen observed in the basement membrane was reduced in smERαKO prostates. Interestingly, these phenotypes were found to be mutually exclusive among smERαKO or fibroblast ERαKO mice. Compound KO of ERα in both fibroblast and smooth muscle showed combined phenotypes from each of the single KO. Further mechanistic studies showed that IGF-I and epidermal growth factor were down-regulated in prostate smooth muscle PS-1 cells lacking ERα. Together, our results indicate the distinct functions of fibroblast vs. smERα in prostate development.

Genetic variation: effect on prostate cancer

PubMed Central

Sissung, Tristan M.; Price, Douglas K.; Del Re, Marzia; Ley, Ariel M.; Giovannetti, Elisa; Danesi, Romano

2014-01-01

Summary The crucial role of androgens in the development of prostate cancer is well established. The aim of this review is to examine the role of constitutional (germline) and tumor-specific (somatic) polymorphisms within important regulatory genes of prostate cancer. These include genes encoding enzymes of the androgen biosynthetic pathway, the androgen receptor gene, genes that encode proteins of the signal transduction pathways that may have a role in disease progression and survival, and genes involved in prostate cancer angiogenesis. Characterization of deregulated pathways critical to cancer cell growth have lead to the development of new treatments, including the CYP17 inhibitor abiraterone and clinical trials using novel drugs that are ongoing or recently completed [1]. The pharmacogenetics of the drugs used to treat prostate cancer will also be addressed. This review will define how germline polymorphisms are known affect a multitude of pathways, and therefore phenotypes, in prostate cancer etiology, progression, and treatment. PMID:25199985

Endocrine disruptors and prostate cancer risk

PubMed Central

Prins, Gail S

2010-01-01

There is increasing evidence both from epidemiology studies and animal models that specific endocrine-disrupting compounds may influence the development or progression of prostate cancer. In large part, these effects appear to be linked to interference with estrogen signaling, either through interacting with ERs or by influencing steroid metabolism and altering estrogen levels within the body. In humans, epidemiologic evidence links specific pesticides, PCBs and inorganic arsenic exposures to elevated prostate cancer risk. Studies in animal models also show augmentation of prostate carcinogenesis with several other environmental estrogenic compounds including cadmium, UV filters and BPA. Importantly, there appears to be heightened sensitivity of the prostate to these endocrine disruptors during the critical developmental windows including in utero and neonatal time points as well as during puberty. Thus infants and children may be considered a highly susceptible population for ED exposures and increased risk of prostate cancers with aging. PMID:18524946

HER2 and EGFR overexpression support metastatic progression of prostate cancer to bone

PubMed Central

Day, Kathleen C.; Hiles, Guadalupe Lorenzatti; Kozminsky, Molly; Dawsey, Scott J.; Paul, Alyssa; Broses, Luke J.; Shah, Rajal; Kunja, Lakshmi P.; Hall, Christopher; Palanisamy, Nallasivam; Daignault-Newton, Stephanie; El-Sawy, Layla; Wilson, Steven James; Chou, Andrew; Ignatoski, Kathleen Woods; Keller, Evan; Thomas, Dafydd; Nagrath, Sunitha; Morgan, Todd; Day, Mark L.

2016-01-01

Activation of the epidermal growth factor receptors EGFR (ErbB1) and HER2 (ErbB2) drive the progression of multiple cancer types through complex mechanisms that are still not fully understood. In this study, we report that HER2 expression is elevated in bone metastases of prostate cancer independently of gene amplification. An examination of HER2 and NF-κB receptor (RANK) coexpression revealed increased levels of both proteins in aggressive prostate tumors and metastatic deposits. Inhibiting HER2 expression in bone tumor xenografts reduced proliferation and RANK expression while maintaining EGFR expression. In examining the role of EGFR in tumor-initiating cells (TIC), we found that EGFR expression was required for primary and secondary sphere formation of prostate cancer cells. EGFR expression was also observed in circulating tumor cells (CTC) during prostate cancer metastasis. Dual inhibition of HER2 and EGFR resulted in significant inhibition of tumor xenograft growth, further supporting the significance of these receptors in prostate cancer progression. Overall, our results indicate that EGFR promotes survival of prostate TIC and CTC that metastasize to bone, whereas HER2 supports the growth of prostate cancer cells once they are established at metastatic sites. PMID:27793843

Intraprostatic injection of botulinum toxin type- A relieves bladder outlet obstruction in human and induces prostate apoptosis in dogs

PubMed Central

Chuang, Yao-Chi; Tu, Chieh-Hsien; Huang, Chao-Cheng; Lin, Hsin-Ju; Chiang, Po-Hui; Yoshimura, Naoki; Chancellor, Michael B

2006-01-01

Background With the increasing interest with botulinum toxin – A (BTX-A) application in the lower urinary tract, we investigated the BTX-A effects on the canine prostate and also in men with bladder outlet obstruction (BOO) due to benign prostatic hyperplasia (BPH). Methods Transperineal injection into the prostate using transrectal ultrasound (TRUS) was performed throughout the study. Saline with or without 100 U of BTX-A was injected into mongrel dogs prostate. One or 3 months later, the prostate was harvested for morphologic and apoptotic study. In addition, eight BPH patients refractory to α-blockers were treated with ultrasound guided intraprostatic injection of 200 U of BTX-A. Results In the BTX-A treated dogs, atrophy and diffuse apoptosis was observed with H&E stain and TUNEL stain at 1 and 3 months. Clinically, the mean prostate volume, symptom score, and quality of life index were significantly reduced by 18.8%, 73.1%, and 61.5% respectively. Maximal flow rate significantly increased by 72.0%. Conclusion Intraprostatic BTX-A injection induces prostate apotosis in dogs and relieves BOO in humans. It is therefore a promising alternative treatment for refractory BOO due to BPH. PMID:16620393

Non-Coding RNAs in Castration-Resistant Prostate Cancer: Regulation of Androgen Receptor Signaling and Cancer Metabolism.

PubMed

Shih, Jing-Wen; Wang, Ling-Yu; Hung, Chiu-Lien; Kung, Hsing-Jien; Hsieh, Chia-Ling

2015-12-04

Hormone-refractory prostate cancer frequently relapses from therapy and inevitably progresses to a bone-metastatic status with no cure. Understanding of the molecular mechanisms conferring resistance to androgen deprivation therapy has the potential to lead to the discovery of novel therapeutic targets for type of prostate cancer with poor prognosis. Progression to castration-resistant prostate cancer (CRPC) is characterized by aberrant androgen receptor (AR) expression and persistent AR signaling activity. Alterations in metabolic activity regulated by oncogenic pathways, such as c-Myc, were found to promote prostate cancer growth during the development of CRPC. Non-coding RNAs represent a diverse family of regulatory transcripts that drive tumorigenesis of prostate cancer and various other cancers by their hyperactivity or diminished function. A number of studies have examined differentially expressed non-coding RNAs in each stage of prostate cancer. Herein, we highlight the emerging impacts of microRNAs and long non-coding RNAs linked to reactivation of the AR signaling axis and reprogramming of the cellular metabolism in prostate cancer. The translational implications of non-coding RNA research for developing new biomarkers and therapeutic strategies for CRPC are also discussed.

Non-Coding RNAs in Castration-Resistant Prostate Cancer: Regulation of Androgen Receptor Signaling and Cancer Metabolism

PubMed Central

Shih, Jing-Wen; Wang, Ling-Yu; Hung, Chiu-Lien; Kung, Hsing-Jien; Hsieh, Chia-Ling

2015-01-01

Hormone-refractory prostate cancer frequently relapses from therapy and inevitably progresses to a bone-metastatic status with no cure. Understanding of the molecular mechanisms conferring resistance to androgen deprivation therapy has the potential to lead to the discovery of novel therapeutic targets for type of prostate cancer with poor prognosis. Progression to castration-resistant prostate cancer (CRPC) is characterized by aberrant androgen receptor (AR) expression and persistent AR signaling activity. Alterations in metabolic activity regulated by oncogenic pathways, such as c-Myc, were found to promote prostate cancer growth during the development of CRPC. Non-coding RNAs represent a diverse family of regulatory transcripts that drive tumorigenesis of prostate cancer and various other cancers by their hyperactivity or diminished function. A number of studies have examined differentially expressed non-coding RNAs in each stage of prostate cancer. Herein, we highlight the emerging impacts of microRNAs and long non-coding RNAs linked to reactivation of the AR signaling axis and reprogramming of the cellular metabolism in prostate cancer. The translational implications of non-coding RNA research for developing new biomarkers and therapeutic strategies for CRPC are also discussed. PMID:26690121

[Expression of SRD5A1 and its prognostic role in prostate cancer: Analysis based on the data-mining of ONCOMINE].

PubMed

Xu, Bin; Liu, Ning; Chen, Shu-Qiu; Jiang, Hua; Zhang, Li-Jie; Zhang, Xiao-Wen; Yang, Yu; Sha, Guo-Zhu; Liu, Jing; Zhu, Wei-Dong; Chen, Ming

2016-09-01

To explore the expression of I-5α-reductase (SRD5A1)and its prognostic role in prostate cancer . Data about SRD5A1 were retrieved from the ONCOMINE database and the role of SRD5A1 in prostate cancer was analyzed. Totally, 992 studies of different types relevant to the expression of SRD5A1 were identified in the ONCOMINE database. The SRD5A1 expression was statistically significant in 239 of the studies, overexpressed in 157 (11 in prostate cancer) and underexpressed in the other 82 (3 in prostate cancer). Eighteen of the studies, with 1 068 samples, addressed the expression of SRD5A1 in prostate cancer and normal tissues, which was significantly higher in the former than in the latter tissue (P<0.05). In 3 of the studies, the SRD5A1 expression was high in primary prostate cancer and increased with its metastasis (P<0.0 5). Two of the studies with prognostic data showed a higher rate of postoperative biochemical recurrence and a higher total mortality rate in the patients with a high than in those with a low expression of SRD5A1 (P<0.05). SRD5A1 is highly expressed in prostate cancer, especially in metastatic and castration-resistant prostate cancer and its expression is associated with the prognosis of prostate cancer, which may be an important target of medication for prostate cancer.

IL‑8 promotes proliferation and inhibition of apoptosis via STAT3/AKT/NF‑κB pathway in prostate cancer.

PubMed

Guo, Yidi; Zang, Ying; Lv, Lianzheng; Cai, Feng; Qian, Tingting; Zhang, Guoying; Feng, Quancheng

2017-12-01

Interleukin-8 (IL-8) possesses tumorigenic and proangiogenic properties, and is overexpressed in many human cancer types. However, only few studies have demonstrated the mechanisms of action of IL‑8 regarding the ability to promote proliferation and to inhibit apoptosis in prostate cancer. Here, the aim of the present study was to investigate the effects of IL‑8 on the prostate cancer cell line and determine possible mechanisms underlying its effect. In this study, IL‑8 was shown to be significantly upregulated in prostate cancer compared with paired normal control tissues. The data showed that IL‑8 exhibits direct oncogenicity, which significantly induced cell proliferation, invasion and attenuated apoptosis in prostate cancer cells via signal transducer and activator of transcription 3/protein kinase B/nuclear factor‑κB signaling pathways. In conclusion, modulation of IL‑8 expression or its associated signaling pathway may provide a novel working mechanism of IL‑8 in prostate cancer, and a promising strategy for controlling the progression and metastasis of prostate cancer.

Effect of Selenium and Vitamin E on Risk of Prostate Cancer and Other Cancers: The Selenium and Vitamin E Cancer Prevention Trial (SELECT)

PubMed Central

Lippman, Scott M.; Klein, Eric A.; Goodman, Phyllis J.; Lucia, M. Scott; Thompson, Ian M.; Ford, Leslie G.; Parnes, Howard L.; Minasian, Lori M.; Gaziano, J. Michael; Hartline, Jo Ann; Parsons, J. Kellogg; Bearden, James D.; Crawford, E. David; Goodman, Gary E.; Claudio, Jaime; Winquist, Eric; Cook, Elise D.; Karp, Daniel D.; Walther, Philip; Lieber, Michael M.; Kristal, Alan R.; Darke, Amy K.; Arnold, Kathryn B.; Ganz, Patricia A.; Santella, Regina M.; Albanes, Demetrius; Taylor, Philip R.; Probstfield, Jeffrey L.; Jagpal, T. J.; Crowley, John J.; Meyskens, Frank L.; Baker, Laurence H.; Coltman, Charles A.

2013-01-01

Context Secondary analyses of two randomized controlled trials (RCTs) and supportive epidemiologic and preclinical indicated the potential of selenium and vitamin E for preventing prostate cancer. Objective To determine whether selenium or vitamin E or both could prevent prostate cancer with little or no toxicity in relatively healthy men. Design, Setting, and Participants Randomization of a planned 32,400 men to selenium, vitamin E, selenium plus vitamin E, and placebo in a double-blinded fashion. Participants were recruited and followed in community practices, local hospitals and HMOs, and tertiary cancer centers in the United States, Canada and Puerto Rico. Baseline eligibility included 50 years or older (African American) or 55 years or older (all others), a serum prostate-specific antigen (PSA) ≤ 4 ng/mL, and a digital rectal examination (DRE) not suspicious for prostate cancer. Between 2001 and 2004, 35,533 men (10% more than planned because of a faster-than-expected accrual rate) were randomly assigned to the four study arms, which were well balanced with respect to all potentially important risk factors. Interventions Oral selenium (200 µg/day from L-selenomethionine) and matched vitamin E placebo, vitamin E (400 IU/day of all rac-α-tocopheryl acetate) and matched selenium placebo, or the two combined or placebo plus placebo for a planned minimum of 7 and maximum of 12 years. Main Outcome Measures Prostate cancer (as determined by routine community diagnostic standards) and prespecified secondary outcomes including lung, colorectal and overall cancer. Results Study supplements were discontinued at the recommendation of the Data and Safety Monitoring Committee at a planned 7-year interim analysis because the evidence convincingly demonstrated no benefit from either study agent (p < 0.0001) and no possibility of a benefit to the planned degree with additional follow-up. As of October 23, 2008, median overall follow-up was 5.46 years (range, 4.17 and 7.33). Hazard ratios (number of prostate cancers, 99% confidence intervals [CIs]) for prostate cancer were 1.13 for vitamin E (n=473; CI, 0.91–1.41), 1.04 for selenium (n=432; CI, 0.83–1.30), and 1.05 for the combination (n=437; CI, 0.83–1.31) compared with placebo (n=416). There were no significant differences (all p-values > 0.15) in any prespecified cancer endpoints. There were nonsignificant increased risks of prostate cancer in the vitamin E arm (p=0.06; relative risk [RR]=1.13; 99% CI, 0l95–1.35) and of Type 2 diabetes mellitus in the selenium arm (p=0.16; RR=1.07; 99% CI, 0.94–1.22), but they were not observed in the combination arm. Conclusion Selenium or vitamin E, alone or in combination, did not prevent prostate cancer in this population at the doses and formulations used. PMID:19066370

Ratio of prostate specific antigen to the outer gland volume of prostrate as a predictor for prostate cancer.

PubMed

Zhang, Hai-Min; Yan, Yang; Wang, Fang; Gu, Wen-Yu; Hu, Guang-Hui; Zheng, Jun-Hua

2014-01-01

As a definite diagnosis of prostate cancer, puncture biopsy of the prostate is invasive method. The aim of this study was to evaluate the value of OPSAD (the ratio of PSA to the outer gland volume of prostate) as a non-invasive screening and diagnosis method for prostate cancer in a select population. The diagnosis data of 490 subjects undergoing ultrasound-guided biopsy of the prostate were retrospectively analyzed. This included 133 patients with prostate cancer, and 357 patients with benign prostate hyperplasia (BPH). The OPSAD was significantly greater in patients with prostate cancer (1.87 ± 1.26 ng/ml(2)) than those with BPH (0.44 ± 0.21 ng/ml(2)) (P < 0.05). Receiver operating characteristic (ROC) curve analysis revealed that the performance of OPSAD as a diagnostic tool is superior to PSA and PSAD for the diagnosis of prostate cancer. In the different groups divided according to the Gleason score of prostate cancer, OPSAD is elevated with the rise of the Gleason score. OPSAD may be used as a new indicator for the diagnosis and prognosis of prostate cancer, and it can reduce the use of unnecessary puncture biopsy of the prostate.

Effect of Whole Pelvic Radiotherapy for Patients With Locally Advanced Prostate Cancer Treated With Radiotherapy and Long-Term Androgen Deprivation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mantini, Giovanna; Tagliaferri, Luca, E-mail: luca.tagliaferri@rm.unicatt.it; Mattiucci, Gian Carlo

2011-12-01

Purpose: To evaluate the effect of whole pelvic radiotherapy (WPRT) in prostate cancer patients treated with RT and long-term (>1 year) androgen deprivation therapy (ADT). Methods and materials: Prostate cancer patients with high-risk features (Stage T3-T4 and/or Gleason score {>=}7 and/or prostate-specific antigen level {>=}20 ng/mL) who had undergone RT and long-term ADT were included in the present analysis. Patients with bowel inflammatory disease, colon diverticula, and colon diverticulitis were excluded from WPRT and treated with prostate-only radiotherapy (PORT). Patients were grouped according to nodal risk involvement as assessed by the Roach formula using different cutoff levels (15%, 20%, 25%,more » and 30%). Biochemical disease-free survival (bDFS) was analyzed in each group according to the RT type (WPRT or PORT). Results: A total of 358 patients treated between 1994 and 2007 were included in the analysis (46.9% with WPRT and 53.1% with PORT). The median duration of ADT was 24 months (range, 12-38). With a median follow-up of 52 months (range, 20-150), the overall 4-year bDFS rate was 90.5%. The 4-year bDFS rate was similar between the patients who had undergone WPRT or PORT (90.4% vs. 90.5%; p = NS). However, in the group of patients with the greatest nodal risk (>30%), a significant bDFS improvement was recorded for the patients who had undergone WPRT (p = .03). No differences were seen in acute toxicity among the patients treated with WPRT or PORT. The late gastrointestinal toxicity was similar in patients treated with PORT or WPRT (p = NS). Conclusions: Our analysis has supported the use of WPRT in association with long-term ADT for patients with high-risk nodal involvement (>30%), although a definitive recommendation should be confirmed by a randomized trial.« less

Prostate Cancer Prevention (PDQ®)—Health Professional Version

Cancer.gov

Prostate cancer prevention strategies include avoiding risk factors, increasing protective factors, and considering chemoprevention when appropriate. Get detailed information about factors that influence the risk of prostate cancer and research aimed at preventing it in this clinician summary.

The Infectious Pathogenesis of Prostate Cancer

DTIC Science & Technology

2010-03-01

of cancers, including prostate. Infections are important agents in the genesis of inflammation. For prostate cancer, several lines of evidence point...to a role of infections as important agents , although no specific infection has consistently been identified. In this project, we are examining two...specific infectious agents with respect to prostate cancer: T vaginalis, the most common non-viral sexually transmitted infection, and the recently

Macrophage Efferocytosis and Prostate Cancer Bone Metastasis

DTIC Science & Technology

2015-10-01

prostate cancer bone metastasis through the phagocytosis of apoptotic tumor cells (efferocytosis). Specific Aims: 1. To identify the phagocytic ...2: To identify the phagocytic /efferocytic macrophage population in the tumor microenvironment of prostate bone metastases and determine its ability...preparation for Cancer Research. We obtained an array of prostate cancer tissue including bone metastasis (N=72) and stained the tissue for the phagocytic

[Changes in prostatic circulation in response to laser therapy and magnetic therapy in patients with benign prostatic hyperplasia].

PubMed

2005-01-01

The results of preoperative preparation were analysed in 59 patients with prostatic benign hyperplasia (PBH) subjected to TUR. Treatment outcomes were assessed by transrectal ultrasound (color Doppler mapping) in two groups of patients. Group 1 received combined therapy including transrectal laser radiation of the prostate, group 2--transrectal magnetotherapy. The analysis showed that laser radiation reduced insignificantly the size of the prostate and adenomatous node, improved microcirculation and circulation in the prostate. This resulted in relief of inflammation and reduction of the number of postoperative inflammatory complications. Transrectal magnetotherapy has a positive effect on vascularization and hemodynamics of the prostate, local immunity, contamination of the tissues with pathogenic flora.

Inherited DNA-Repair Gene Mutations in Men with Metastatic Prostate Cancer.

PubMed

Pritchard, Colin C; Mateo, Joaquin; Walsh, Michael F; De Sarkar, Navonil; Abida, Wassim; Beltran, Himisha; Garofalo, Andrea; Gulati, Roman; Carreira, Suzanne; Eeles, Rosalind; Elemento, Olivier; Rubin, Mark A; Robinson, Dan; Lonigro, Robert; Hussain, Maha; Chinnaiyan, Arul; Vinson, Jake; Filipenko, Julie; Garraway, Levi; Taplin, Mary-Ellen; AlDubayan, Saud; Han, G Celine; Beightol, Mallory; Morrissey, Colm; Nghiem, Belinda; Cheng, Heather H; Montgomery, Bruce; Walsh, Tom; Casadei, Silvia; Berger, Michael; Zhang, Liying; Zehir, Ahmet; Vijai, Joseph; Scher, Howard I; Sawyers, Charles; Schultz, Nikolaus; Kantoff, Philip W; Solit, David; Robson, Mark; Van Allen, Eliezer M; Offit, Kenneth; de Bono, Johann; Nelson, Peter S

2016-08-04

Inherited mutations in DNA-repair genes such as BRCA2 are associated with increased risks of lethal prostate cancer. Although the prevalence of germline mutations in DNA-repair genes among men with localized prostate cancer who are unselected for family predisposition is insufficient to warrant routine testing, the frequency of such mutations in patients with metastatic prostate cancer has not been established. We recruited 692 men with documented metastatic prostate cancer who were unselected for family history of cancer or age at diagnosis. We isolated germline DNA and used multiplex sequencing assays to assess mutations in 20 DNA-repair genes associated with autosomal dominant cancer-predisposition syndromes. A total of 84 germline DNA-repair gene mutations that were presumed to be deleterious were identified in 82 men (11.8%); mutations were found in 16 genes, including BRCA2 (37 men [5.3%]), ATM (11 [1.6%]), CHEK2 (10 [1.9% of 534 men with data]), BRCA1 (6 [0.9%]), RAD51D (3 [0.4%]), and PALB2 (3 [0.4%]). Mutation frequencies did not differ according to whether a family history of prostate cancer was present or according to age at diagnosis. Overall, the frequency of germline mutations in DNA-repair genes among men with metastatic prostate cancer significantly exceeded the prevalence of 4.6% among 499 men with localized prostate cancer (P<0.001), including men with high-risk disease, and the prevalence of 2.7% in the Exome Aggregation Consortium, which includes 53,105 persons without a known cancer diagnosis (P<0.001). In our multicenter study, the incidence of germline mutations in genes mediating DNA-repair processes among men with metastatic prostate cancer was 11.8%, which was significantly higher than the incidence among men with localized prostate cancer. The frequencies of germline mutations in DNA-repair genes among men with metastatic disease did not differ significantly according to age at diagnosis or family history of prostate cancer. (Funded by Stand Up To Cancer and others.).

αVβ6 integrin expression is induced in the POET and Ptenpc-/- mouse models of prostatic inflammation and prostatic adenocarcinoma

PubMed Central

Garlick, David S; Li, Jing; Sansoucy, Brian; Wang, Tao; Griffith, Leeanne; FitzGerald, TJ; Butterfield, Julie; Charbonneau, Bridget; Violette, Shelia M; Weinreb, Paul H; Ratliff, Timothy L; Liao, Chun-Peng; Roy-Burman, Pradip; Vietri, Michele; Lian, Jane B; Stein, Gary S; Altieri, Dario C; Languino, Lucia R

2012-01-01

Chronic inflammation is proposed to prime the development of prostate cancer. However, the mechanisms of prostate cancer initiation and development are not completely understood. The αvβ6 integrin has been shown to play a role in epithelial development, wound healing and some epithelial cancers [1, 2]. Here, we investigate the expression of αvβ6 in mouse models of prostatic inflammation and prostate cancer to establish a possible relationship between inflammation of the prostate, αvβ6 expression and the progression of prostate cancer. Using immunohistochemical techniques, we show expression of αvβ6 in two in vivo mouse models; the Ptenpc-/- model containing a prostate- specific Pten tumor suppressor deletion that causes cancer, and the prostate ovalbumin-expressing transgenic (POET) inflammation mouse model. We show that the αvβ6 integrin is induced in prostate cancer and inflammation in vivo in these two mouse models. αvβ6 is expressed in all the mice with cancer in the Ptenpc-/- model but not in age-matched wild-type mice. In the POET inflammation model, αvβ6 is expressed in mice injected with activated T-cells, but in none of the control mice. In the POET model, we also used real time PCR to assess the expression of Transforming Growth Factor Beta 1 (TGFβ1), a factor in inflammation that is activated by αvβ6. In conclusion, through in vivo evidence, we conclude that αvβ6 integrin may be a crucial link between prostatic inflammation and prostatic adenocarcinoma. PMID:22611469

α(V)β(6) integrin expression is induced in the POET and Pten(pc-/-) mouse models of prostatic inflammation and prostatic adenocarcinoma.

PubMed

Garlick, David S; Li, Jing; Sansoucy, Brian; Wang, Tao; Griffith, Leeanne; Fitzgerald, Tj; Butterfield, Julie; Charbonneau, Bridget; Violette, Shelia M; Weinreb, Paul H; Ratliff, Timothy L; Liao, Chun-Peng; Roy-Burman, Pradip; Vietri, Michele; Lian, Jane B; Stein, Gary S; Altieri, Dario C; Languino, Lucia R

2012-01-01

Chronic inflammation is proposed to prime the development of prostate cancer. However, the mechanisms of prostate cancer initiation and development are not completely understood. The α(v)β(6) integrin has been shown to play a role in epithelial development, wound healing and some epithelial cancers [1, 2]. Here, we investigate the expression of α(v)β(6) in mouse models of prostatic inflammation and prostate cancer to establish a possible relationship between inflammation of the prostate, α(v)β(6) expression and the progression of prostate cancer. Using immunohistochemical techniques, we show expression of α(v)β(6) in two in vivo mouse models; the Pten(pc)-/- model containing a prostate- specific Pten tumor suppressor deletion that causes cancer, and the prostate ovalbumin-expressing transgenic (POET) inflammation mouse model. We show that the α(v)β(6) integrin is induced in prostate cancer and inflammation in vivo in these two mouse models. α(v)β(6) is expressed in all the mice with cancer in the Pten(pc-/-) model but not in age-matched wild-type mice. In the POET inflammation model, α(v)β(6) is expressed in mice injected with activated T-cells, but in none of the control mice. In the POET model, we also used real time PCR to assess the expression of Transforming Growth Factor Beta 1 (TGFβ1), a factor in inflammation that is activated by α(v)β(6). In conclusion, through in vivo evidence, we conclude that α(v)β(6) integrin may be a crucial link between prostatic inflammation and prostatic adenocarcinoma.

Racial and Ethnic Variation in Time to Prostate Biopsy After an Elevated Screening Level of Serum Prostate-specific Antigen.

PubMed

Reading, Stephanie R; Porter, Kimberly R; Hsu, Jin-Wen Y; Wallner, Lauren P; Loo, Ronald K; Jacobsen, Steven J

2016-10-01

To examine the racial and ethnic variation in time to prostate biopsy after an elevated screening level of serum prostate-specific antigen (PSA). Male members of the Kaiser Permanente of Southern California health plan, 45 years of age or older, with no history of prostate cancer or a prostate biopsy, and at least 1 elevated screening level of serum PSA between January 1, 1998 and December 31, 2007 were retrospectively identified (n = 59,506). All participants were passively followed via electronic health records until their time of prostate biopsy, death, membership disenrollment, or study conclusion (December 31, 2014), whichever was the initial event. Proportional hazard regression analyses were used to estimate the association between time from an elevated screening level of serum PSA to prostate biopsy, adjusting for age, benign prostatic hyperplasia, prostatitis, type 2 diabetes mellitus, hypertension, and Charlson Comorbidity Index score. Median time until biopsy was 0.6 years (214 days), with approximately 41% of participants receiving a prostate biopsy within the study period. Results from the fully adjusted analysis indicated that the non-Hispanic Asian or Pacific Islanders (hazard ratio: 1.10, 95% confidence interval: [1.04, 1.15]) and the non-Hispanic blacks (hazard ratio: 1.04, 95% confidence interval: [1.00, 1.08]) had a slightly shorter time to prostate biopsy after an elevated screening level of serum PSA compared to the non-Hispanic whites. These data suggest that, within an integrated healthcare organization, minimal differences exist between racial and ethnic subgroups in their time to prostate biopsy after an elevated screening level of serum PSA. Copyright © 2016. Published by Elsevier Inc.

Screening for prostate cancer

NASA Technical Reports Server (NTRS)

Weirich, Stephen A.

1993-01-01

Despite recent advances in both the survival and cure rates for many forms of cancer, unfortunately the same has not been true for prostate cancer. In fact, the age-adjusted death rate from prostate cancer has not significantly improved since 1949, and prostate cancer remains the most common cancer in American men, causing the second highest cancer mortality rate. Topics discussed include the following: serum testosterone levels; diagnosis; mortality statistics; prostate-sppecific antigen (PSA) tests; and the Occupational Medicine Services policy at LeRC.

Prostate cancer molecular detection in plasma samples by glutathione S-transferase P1 (GSTP1) methylation analysis.

PubMed

Dumache, Raluca; Puiu, Maria; Motoc, Marilena; Vernic, Corina; Dumitrascu, Victor

2014-01-01

Prostate cancer (PCa) represents the most commonly diagnosed type of malignancy among men in Western European countries and the second cause of cancer-related deaths among men worldwide. Methylation of the CpG island has an important role in prostate carcinogenesis and progression. The purpose of the study was to analyse the diagnostic value of aberrant promoter hypermethylation of the gene for glutathione S-transferase P1 (GSTP1) in plasma DNA to discriminate between prostate cancer (PCa) and benign prostatic hyperplasia (BPH) patients by minimally invasive methods. Aberrant promoter hypermethylation was investigated in DNA isolated from plasma samples of 31 patients with diagnostic of PCa and 44 cancer-free males (control subjects). Extracted genomic DNA was bisulfite treated and analyzed using methylation-specific polymerase chain reaction (MS-PCR) technique. Hypermethylation of the GSTP1 gene was detected in plasma samples from 27 of 31 (92.86%) patients with PCa. Genomic DNA from plasma samples from the 44 controls without genitourinary cancer revealed promoter hypermethylation of GSTP1 gene in 3 (10.6%) of the 44 patients. Receiver operating curve (ROC) included clinico-pathological parameters such as: serum PSA levels, pathological stage, Gleason score, hypermethylation status of GSTP1 gene, and it gave a predictive accuracy of 93% with a sensitivity and specificity of 95% and 87%, respectively. In this study, we have evaluated the ability of GSTP1 gene to discriminate between PCa and BPH patients in genomic DNA from plasma samples by non-invasive methods.

Caregiving and Social Support for Gay and Bisexual Men with Prostate Cancer

PubMed Central

Capistrant, Benjamin D.; Torres, Beatriz; Merengwa, Enyinnaya; West, William G.; Mitteldorf, Darryl; Simon Rosser, B. R.

2017-01-01

Objective Prostate cancer, the second most common cancer among men, typically onsets in middle or older age. Gay/bisexual men have different social networks and unique social support needs, particularly as it pertains to health care access and prostate side effects. Few studies have investigated the availability and provision of social support for gay and bisexual men with prostate cancer (GBMPCa). Methods This study used qualitative data from in-depth, semi-structured, one-on-one telephone interviews with 30 GBMPCa recruited from a national cancer support group network, Malecare. Inductive and deductive coding were used to identify themes about social support provided to GBMPCa during diagnosis and treatment. Results GBMPCa reported help from friends, family (parents, siblings), ex-partners, and paid caregivers. Men in relationships reported varying levels of reliance on their partners for support, in part due to relationship dynamics and living arrangements. Single men showed a theme of independence (“I turned down all help”, “my friends don’t want to be bothered”). After diagnosis, many men reported seeking informational and emotional support from prostate cancer support groups; most expressed wanting more support groups specifically for GBMPCa. During or after treatment, men reported receiving a range of instrumental support, largely a function of relationship status and treatment type. Conclusions GBMPCa received variable, but generally low, social support during diagnosis and treatment and from a diverse social network, including a prominence of friends and family. Clinicians should be aware of GBMPCa’s distinct patterns of social support needs and providers. PMID:27530377

Caregiving and social support for gay and bisexual men with prostate cancer.

PubMed

Capistrant, Benjamin D; Torres, Beatriz; Merengwa, Enyinnaya; West, William G; Mitteldorf, Darryl; Rosser, B R Simon

2016-11-01

Prostate cancer, the second most common cancer among men, typically onsets in middle or older age. Gay/bisexual men have different social networks and unique social support needs, particularly as it pertains to health care access and prostate side effects. Few studies have investigated the availability and provision of social support for gay and bisexual men with prostate cancer (GBMPCa). This study used qualitative data from in-depth, semistructured, one-on-one telephone interviews with 30 GBMPCa recruited from a national cancer support group network, Malecare. Inductive and deductive codes were used to identify themes about social support provided to GBMPCa during diagnosis and treatment. GBMPCa reported help from friends, family (parents and siblings), ex-partners, and paid caregivers. Men in relationships reported varying levels of reliance on their partners for support, in part due to relationship dynamics and living arrangements. Single men showed a theme of independence ("I turned down all help," "My friends don't want to be bothered"). After diagnosis, many men reported seeking informational and emotional support from prostate cancer support groups; most expressed wanting more support groups specifically for GBMPCa. During or after treatment, men reported receiving a range of instrumental support, largely a function of relationship status and treatment type. GBMPCa received variable, but generally low, social support during diagnosis and treatment and from a diverse social network, including a prominence of friends and family. Clinicians should be aware of GBMPCa's distinct patterns of social support needs and providers. Copyright © 2016 John Wiley & Sons, Ltd.

Low-level arsenic exposure from drinking water is associated with prostate cancer in Iowa.

PubMed

Roh, Taehyun; Lynch, Charles F; Weyer, Peter; Wang, Kai; Kelly, Kevin M; Ludewig, Gabriele

2017-11-01

Inorganic arsenic is a toxic naturally occurring element in soil and water in many regions of the US including the Midwest. Prostate cancer is the second most common type of cancer in men in Iowa, surpassed only by non-melanotic skin cancer. Epidemiology studies have evaluated arsenic exposure from drinking water and prostate cancer, but most have focused on high-level exposures outside the US. As drinking water from groundwater sources is a major source of arsenic exposure, we conducted an ecologic study to evaluate prostate cancer and arsenic in drinking water from public water sources and private wells in Iowa, where exposure levels are low, but duration of exposure can be long. Arsenic data from public water systems were obtained from the Iowa Safe Drinking Water Information System for the years 1994-2003 and for private wells from two Iowa Well Water Studies, the Iowa Community Private Well Study (ICPWS, 2002-2003) and Iowa Statewide Rural Well Water Survey Phase 2 (SWIRL2, 2006-2008) that provided data for 87 Iowa counties. Prostate cancer incidence data from 2009 to 2013 for Iowa were obtained from Surveillance, Epidemiology and End Results' SEER*Stat software. County averages of water arsenic levels varied from 1.08 to 18.6 ppb, with three counties above the current 10 ppb limit. Based on the tertiles of arsenic levels, counties were divided into three groups: low (1.08-2.06 ppb), medium (2.07-2.98 ppb), and high (2.99-18.6 ppb). Spatial Poisson regression modeling was conducted to estimate the risk ratios (RR) of prostate cancer by tertiles of arsenic level at a county level, adjusted for demographic and risk factors. The RR of prostate cancer were 1.23 (95% CI, 1.16-1.30) and 1.28 (95% CI, 1.21-1.35) in the medium and high groups, respectively, compared to the low group after adjusting for risk factors. The RR increased to 1.36 (95% CI, 1.28-1.45) in the high group when analyses were restricted to aggressive prostate cancers (Gleason score ≥ 7). This study shows a significant dose-dependent association between low-level arsenic exposure and prostate cancer, and if this result is replicated in future individual-level studies, may suggest that 10 ppb is not protective for human health. Copyright © 2017 Elsevier Inc. All rights reserved.

Epigenetic Control of Prostate Cancer Metastasis: Role of Runx2 Phosphorylation

DTIC Science & Technology

2014-04-01

prostate cancer cells. In the third budget year, we achieved the following: a. Generation of retrovirus and lentivirus vectors expressing WT RUNX2 and S301A... retrovirus vectors will be developed that express β-galactosidase (negative control), wild type Runx2, S301A/S319A (non-phosphorylated) or S301E/S310E...constitutively active) Runx2 mutants. As described last year, retrovirus and lentivirus vectors were constructed to stably introduce wild type and mutant

Development of a PET Prostate-Specific Membrane Antigen Imaging Agent: Preclinical Translation for Future Clinical Application

DTIC Science & Technology

2017-10-01

94103 REPORT DATE : October 2017 TYPE OF REPORT: Annual PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland...display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE October 2017 2. REPORT TYPE...Annual 3. DATES COVERED 30 Sep 2016 - 29 Sep 2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Development of a PET Prostate-Specific Membrane Antigen

High-Resolution Radioluminescence Microscopy for the Study of Prostate Tissue Slice Cell Metabolism and Monitoring of Treatment Response

DTIC Science & Technology

2015-09-01

University, The Stanford CA 94305-2004 REPORT DATE : October 2015 TYPE OF REPORT: annual PREPARED FOR: U.S. Army Medical Research and Materiel... DATE (DD-MM-YYYY) October 2015 2. REPORT TYPE Annual Report 3. DATES COVERED (From - To) 30 Sep 2014 - 29 Sep 2015 4. TITLE AND SUBTITLE Monitoring...ABSTRACT Currently, prostate cancers are classified using the Gleason Grade system and immunohistochemistry. The shortcoming of this method is that

Transurethral lithotripsy with holmium-YAG laser of a large exogenous prostatic calculus.

PubMed

Hasegawa, Masanori; Ohara, Rei; Kanao, Kent; Nakajima, Yosuke

2011-04-01

Prostatic calculi are classified into two types, endogenous and exogenous calculi, based on their origin. Endogenous calculi are commonly observed in elderly men; however, exogenous prostatic calculi are extremely rare. We report here the case of a 51-year-old man who suffered incontinence and pollakiuria with a giant exogenous prostatic calculus almost completely replacing the prostatic tissue. X-rays and computed tomography demonstrated a large calculus of 65 × 58 mm in the small pelvic cavity. The patient underwent a transurethral lithotripsy with a holmium-YAG laser and a total of 85 g of disintegrated stones was retrieved and chemical stone analysis revealed the presence of magnesium ammonium phosphate. The incontinence improved and the voiding volume increased dramatically, and no stone recurrence in the prostatic fossa occurred at the 2 years follow-up. The etiology of this stone formation seemed to be based on some exogenous pathways combined with urinary stasis and chronic urinary infection due to compression fracture of the lumbar vertebra.

[11C]choline-PET-guided helical tomotherapy and estramustine in a patient with pelvic-recurrent prostate cancer: local control and toxicity profile after 24 months.

PubMed

Alongi, Filippo; Schipani, Stefano; Samanes Gajate, Ana Maria; Rosso, Alberto; Cozzarini, Cesare; Fiorino, Claudio; Alongi, Pierpaolo; Picchio, Maria; Gianolli, Luigi; Messa, Cristina; Di Muzio, Nadia

2010-01-01

[11C]choline positron emission tomograhy can be useful to detect metastatic disease and to localize isolated lymph node relapse after primary treatment in case of prostate-specific antigen failure. In case of lymph node failure in prostate cancer patients, surgery or radiotherapy can be proposed with a curative intent. Some reports have suggested that radiotherapy could have a role in local control of oligometastatic lymph node disease. This is the first reported case of [11C]choline positron emission tomography-guided helical tomotherapy concomitant with estramustine for the treatment of pelvic-recurrent prostate cancer. At 24 months after the end of helical tomotherapy, prostate-specific antigen was undetectable and no late toxicities were recorded. A disease-free survival of 24 months, in the absence of any type of systemic therapy, is uncommon in metastatic prostate cancer. The therapeutic approach of the case report is discussed and a literature review on the issue is presented.

The oncogenic gene fusion TMPRSS2: ERG is not a diagnostic or prognostic marker for ovarian cancer

PubMed Central

Huang, Lillian; Schauer, Isaiah G; Zhang, Jing; Mercado-Uribe, Imelda; Deavers, Michael T; Huang, Jiaoti; Liu, Jinsong

2011-01-01

TMPRSS2:ERG is a gene fusion resulting from the chromosomal rearrangement of the androgen-regulated TMPRSS2 gene and the ETS transcription factor ERG, leading to the over-expression of the oncogenic molecule ERG. This gene rearrangement has been found in approximately half of all prostate cancers and ERG overexpression is considered as a novel diagnostic marker for prostate carcinoma. However, little is known about the role of the TMPRSS2:ERG gene fusion in ovarian cancer. The purpose of this study was to test ERG expression in ovarian cancer and its potential as a diagnostic marker for ovarian carcinoma progression. A tissue microarray containing 180 ovarian cancer tissues of various pathological types and grades were examined by immunohistochemical analysis for expression of ERG. We also used 40 prostate carcinoma tissues and 40 normal tissues for comparison in parallel experiments. ERG-positive expression was detected in 40% of the prostate tumor cancer, as well as in internal positive control endothelial cells, confirming over-expression of ERG in prostate cancer at relatively the same rate observed by others. In contrast, all of the ovarian tumor patient tissues of varying histologic types were ERG-negative, despite some positivity in endothelial cells. These results suggest that the oncogenic gene fusion TMPRSS2:ERG does not occur in ovarian cancer relative to prostate cancer. Therefore, development of ERG expression profile would not be a useful diagnostic or prognostic marker for ovarian cancer patient screening. PMID:22076164

The oncogenic gene fusion TMPRSS2: ERG is not a diagnostic or prognostic marker for ovarian cancer.

PubMed

Huang, Lillian; Schauer, Isaiah G; Zhang, Jing; Mercado-Uribe, Imelda; Deavers, Michael T; Huang, Jiaoti; Liu, Jinsong

2011-01-01

TMPRSS2:ERG is a gene fusion resulting from the chromosomal rearrangement of the androgen-regulated TMPRSS2 gene and the ETS transcription factor ERG, leading to the over-expression of the oncogenic molecule ERG. This gene rearrangement has been found in approximately half of all prostate cancers and ERG overexpression is considered as a novel diagnostic marker for prostate carcinoma. However, little is known about the role of the TMPRSS2:ERG gene fusion in ovarian cancer. The purpose of this study was to test ERG expression in ovarian cancer and its potential as a diagnostic marker for ovarian carcinoma progression. A tissue microarray containing 180 ovarian cancer tissues of various pathological types and grades were examined by immunohistochemical analysis for expression of ERG. We also used 40 prostate carcinoma tissues and 40 normal tissues for comparison in parallel experiments. ERG-positive expression was detected in 40% of the prostate tumor cancer, as well as in internal positive control endothelial cells, confirming over-expression of ERG in prostate cancer at relatively the same rate observed by others. In contrast, all of the ovarian tumor patient tissues of varying histologic types were ERG-negative, despite some positivity in endothelial cells. These results suggest that the oncogenic gene fusion TMPRSS2:ERG does not occur in ovarian cancer relative to prostate cancer. Therefore, development of ERG expression profile would not be a useful diagnostic or prognostic marker for ovarian cancer patient screening.

Clinical outcomes and nadir prostate-specific antigen (PSA) according to initial PSA levels in primary androgen deprivation therapy for metastatic prostate cancer.

PubMed

Kitagawa, Yasuhide; Ueno, Satoru; Izumi, Kouji; Kadono, Yoshifumi; Mizokami, Atsushi; Hinotsu, Shiro; Akaza, Hideyuki; Namiki, Mikio

2016-03-01

To investigate the clinical outcomes of metastatic prostate cancer patients and the relationship between nadir prostate-specific antigen (PSA) levels and different types of primary androgen deprivation therapy (PADT). This study utilized data from the Japan Study Group of Prostate Cancer registry, which is a large, multicenter, population-based database. A total of 2982 patients treated with PADT were enrolled. Kaplan-Meier analysis was used to compare progression-free survival (PFS) and overall survival (OS) in patients treated using combined androgen blockade (CAB) and non-CAB therapies. The relationships between nadir PSA levels and PADT type according to initial serum PSA levels were also investigated. Among the 2982 enrolled patients, 2101 (70.5 %) were treated with CAB. Although CAB-treated patients had worse clinical characteristics, their probability of PFS and OS was higher compared with those treated with a non-CAB therapy. These results were due to a survival benefit with CAB in patients with an initial PSA level of 500-1000 ng/mL. Nadir PSA levels were significantly lower in CAB patients than in non-CAB patients with comparable initial serum PSA levels. A small survival benefit for CAB in metastatic prostate cancer was demonstrated in a Japanese large-scale prospective cohort study. The clinical significance of nadir PSA levels following PADT was evident, but the predictive impact of PSA nadir on OS was different between CAB and non-CAB therapy.

78 FR 24750 - Scientific Information Request Therapies for Clinically Localized Prostate Cancer

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-26

... and benefits of the following therapies for clinically localized prostate cancer? a. Radical... prostate cancer: radical prostatectomy (including retropubic, perineal, laparoscopic, robotic-assisted..., biochemical (PSA) progression, metastatic and/or clinical progression-free survival, health status, and...

The Natural History of Erectile Dysfunction After Prostatic Radiotherapy: A Systematic Review and Meta-Analysis.

PubMed

Gaither, Thomas W; Awad, Mohannad A; Osterberg, E Charles; Murphy, Gregory P; Allen, Isabel E; Chang, Albert; Rosen, Raymond C; Breyer, Benjamin N

2017-09-01

Erectile dysfunction (ED) after treatment for prostate cancer with radiotherapy (RT) is well known, and pooled estimates of ED after RT will provide more accurate patient education. To systematically evaluate the natural history of ED in men with previous erectile function after prostate RT and to determine clinical factors associated with ED. We performed a review of the PubMed and Medline, Embase, Cochrane Library, and Web of Science databases in April 2016 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Identified reports included a measurement of ED before and after prostate RT. Two hundred seventy-eight abstracts were screened and 105 publications met the criteria for inclusion. Only men with known erectile function before RT were included in the analysis. ED after RT of the prostate. In total, 17,057 men underwent brachytherapy (65%), 8,166 men underwent external-beam RT (31%), and 1,046 men underwent both (4%). Seven common instruments were used to measure ED, including 23 different cutoffs for ED. The Sexual Health Inventory for Men (SHIM) was used in 31 studies (30%). Pooled estimates of SHIM-confirmed ED (score <10-17) suggested the prevalence of ED after RT is 34% of men (95% CI = 0.29-0.39) at 1 year and 57% (95% CI = 0.53-0.61) at 5.5 years. Compared with brachytherapy, studies of the two types of radiation increased the proportion of new-onset ED found by 12.3% of studies (95% CI = 2.3-22.4). For every 10% who were lost to follow-up, the proportion of ED reported increased by 2.3% (95% CI = 0.03-4.7). ED is common regardless of RT modality and increases during each year of follow-up. Using the SHIM, ED is found in approximately 50% patients at 5 years. The strengths of this systematic review include strict inclusion criteria of studies that measured baseline erectile function, no evidence for large effect size bias, and a large number of studies, which allow for modeling techniques. However, all data included in this analysis were observational, which leaves the possibility that residual confounding factors increase the rates of ED. Definitions and measurements of ED after RT vary considerably in published series and could account for variability in the prevalence of reported ED. Loss to follow-up in studies could bias the results to overestimate ED. Gaither TW, Awad MA, Osterberg EC, et al. The Natural History of Erectile Dysfunction After Prostatic Radiotherapy: A Systematic Review and Meta-Analysis. J Sex Med 2017;14:1071-1078. Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

RNA splicing and splicing regulator changes in prostate cancer pathology.

PubMed

Munkley, Jennifer; Livermore, Karen; Rajan, Prabhakar; Elliott, David J

2017-09-01

Changes in mRNA splice patterns have been associated with key pathological mechanisms in prostate cancer progression. The androgen receptor (abbreviated AR) transcription factor is a major driver of prostate cancer pathology and activated by androgen steroid hormones. Selection of alternative promoters by the activated AR can critically alter gene function by switching mRNA isoform production, including creating a pro-oncogenic isoform of the normally tumour suppressor gene TSC2. A number of androgen-regulated genes generate alternatively spliced mRNA isoforms, including a prostate-specific splice isoform of ST6GALNAC1 mRNA. ST6GALNAC1 encodes a sialyltransferase that catalyses the synthesis of the cancer-associated sTn antigen important for cell mobility. Genetic rearrangements occurring early in prostate cancer development place ERG oncogene expression under the control of the androgen-regulated TMPRSS2 promoter to hijack cell behaviour. This TMPRSS2-ERG fusion gene shows different patterns of alternative splicing in invasive versus localised prostate cancer. Alternative AR mRNA isoforms play a key role in the generation of prostate cancer drug resistance, by providing a mechanism through which prostate cancer cells can grow in limited serum androgen concentrations. A number of splicing regulator proteins change expression patterns in prostate cancer and may help drive key stages of disease progression. Up-regulation of SRRM4 establishes neuronal splicing patterns in neuroendocrine prostate cancer. The splicing regulators Sam68 and Tra2β increase expression in prostate cancer. The SR protein kinase SRPK1 that modulates the activity of SR proteins is up-regulated in prostate cancer and has already given encouraging results as a potential therapeutic target in mouse models.

Common Questions About Chronic Prostatitis.

PubMed

Holt, James D; Garrett, W Allan; McCurry, Tyler K; Teichman, Joel M H

2016-02-15

Chronic prostatitis is relatively common, with a lifetime prevalence of 1.8% to 8.2%. Risk factors include conditions that facilitate introduction of bacteria into the urethra and prostate (which also predispose the patient to urinary tract infections) and conditions that can lead to chronic neuropathic pain. Chronic prostatitis must be differentiated from other causes of chronic pelvic pain, such as interstitial cystitis/bladder pain syndrome and pelvic floor dysfunction; prostate and bladder cancers; benign prostatic hyperplasia; urolithiasis; and other causes of dysuria, urinary frequency, and nocturia. The National Institutes of Health divides prostatitis into four syndromes: acute bacterial prostatitis, chronic bacterial prostatitis (CBP), chronic nonbacterial prostatitis (CNP)/chronic pelvic pain syndrome (CPPS), and asymptomatic inflammatory prostatitis. CBP and CNP/CPPS both lead to pelvic pain and lower urinary tract symptoms. CBP presents as recurrent urinary tract infections with the same organism identified on repeated cultures; it responds to a prolonged course of an antibiotic that adequately penetrates the prostate, if the urine culture suggests sensitivity. If four to six weeks of antibiotic therapy is effective but symptoms recur, another course may be prescribed, perhaps in combination with alpha blockers or nonopioid analgesics. CNP/CPPS, accounting for more than 90% of chronic prostatitis cases, presents as prostatic pain lasting at least three months without consistent culture results. Weak evidence supports the use of alpha blockers, pain medications, and a four- to six-week course of antibiotics for the treatment of CNP/CPPS. Patients may also be referred to a psychologist experienced in managing chronic pain. Experts on this condition recommend a combination of treatments tailored to the patient's phenotypic presentation. Urology referral should be considered when appropriate treatment is ineffective. Additional treatments include pelvic floor physical therapy, phytotherapy, and pain management techniques. The UPOINT (urinary, psychosocial, organ-specific, infection, neurologic/systemic, tenderness) approach summarizes the various factors that may contribute to presentation and can guide treatment.

Combined spectroscopic imaging and chemometric approach for automatically partitioning tissue types in human prostate tissue biopsies

NASA Astrophysics Data System (ADS)

Haka, Abigail S.; Kidder, Linda H.; Lewis, E. Neil

2001-07-01

We have applied Fourier transform infrared (FTIR) spectroscopic imaging, coupling a mercury cadmium telluride (MCT) focal plane array detector (FPA) and a Michelson step scan interferometer, to the investigation of various states of malignant human prostate tissue. The MCT FPA used consists of 64x64 pixels, each 61 micrometers 2, and has a spectral range of 2-10.5 microns. Each imaging data set was collected at 16-1 resolution, resulting in 512 image planes and a total of 4096 interferograms. In this article we describe a method for separating different tissue types contained within FTIR spectroscopic imaging data sets of human prostate tissue biopsies. We present images, generated by the Fuzzy C-Means clustering algorithm, which demonstrate the successful partitioning of distinct tissue type domains. Additionally, analysis of differences in the centroid spectra corresponding to different tissue types provides an insight into their biochemical composition. Lastly, we demonstrate the ability to partition tissue type regions in a different data set using centroid spectra calculated from the original data set. This has implications for the use of the Fuzzy C-Means algorithm as an automated technique for the separation and examination of tissue domains in biopsy samples.

Benign prostatic hyperplasia (BPH) management in the primary care setting.

PubMed

Kapoor, Anil

2012-10-01

Benign prostate hyperplasia (BPH) occurs in up to 50% of men by age 50, and the incidence increases with age. This common clinical problem is diagnosed by history, including the International Prostate Symptom Score (IPSS) questionnaire, and physical examination by digital rectal examination (DRE). Initial management for BPH includes lifestyle modification, and smooth muscle relaxant alpha blocker therapy. Alpha blockers usually take effect quickly within 3-5 days, and have minimal side effects. Current commonly used alpha blockers include the selective alpha blockers tamsulosin (Flomax), alfusosin (Xatral), and silodosin (Rapaflo). For patients with larger prostates, the 5-alpha reductase inhibitor class (finasteride (Proscar) and dutasteride (Avodart)) work effectively to shrink prostate stroma resulting in improved voiding. The 5-ARI class of drugs, in addition to reducing prostate size, also reduce the need for future BPH-related surgery, and reduce the risk of future urinary retention. Drugs from the phosphodiesterase-5 (PDE-5) inhibitor class may now be considered for treating BPH. Once daily 5 mg tadalafil has been shown to improve BPH-related symptoms and is currently approved to treat patients with BPH. Referral to a urologist can be considered for patients with a rising prostate-specific antigen (PSA), especially while on 5-ARI, failure of urinary symptom control despite maximal medical therapy, suspicion of prostate cancer, hematuria, recurrent urinary infections, urinary retention, or renal failure. Currently the primary care physician is armed with multiple treatment options to effectively treat men with symptomatic BPH.

Gonorrhea infection increases the risk of prostate cancer in Asian population: a nationwide population-based cohort study.

PubMed

Wang, Y-C; Chung, C-H; Chen, J-H; Chiang, M-H; Ti-Yin; Tsao, C-H; Lin, F-H; Chien, W-C; Shang, S-T; Chang, F-Y

2017-05-01

This nationwide population-based retrospective cohort study evaluated the risk of developing prostate cancer among patients with gonorrhea. We identified cases of newly diagnosed gonorrhea in men between 2000 and 2010 from the Taiwan National Health Insurance Research Database. Each patient with gonorrhea was matched to four controls, based on age and index year. All subjects were followed up from the index date to December 31, 2010. The Cox proportional hazards regression model was used to assess the risk of prostate cancer. A total of 355 men were included in the study group, and 1,420 age-matched subjects without gonorrhea were included in the control group. After adjusting for age, comorbidities, urbanization level, hospital level, and monthly income, gonorrhea was significantly associated with an increased risk of prostate cancer (adjusted hazard ratio = 5.66, 95% confidence interval = 1.36-23.52). Men aged 45-70 years and those with lower monthly income were more strongly associated with prostate cancer in the study group than the control group. The higher risk for developing prostate cancer were also found in those without syphilis, without genital warts, without diabetes mellitus, without chronic obstructive pulmonary disease, without benign prostatic hypertrophy, without chronic prostatitis, and without alcoholism. The Kaplan-Meier analysis showed the risk of prostate cancer was significantly higher in the study group than in the control group. Gonorrhea may be involved in the development of prostate cancer. More intensive screening and prevention interventions for prostate cancer should be recommended in men with gonorrhea.

Current Perspectives on Novel Drug Delivery Systems and Therapies for Management of Prostate Cancer: An Inclusive Review.

PubMed

Bhosale, Rohit R; Gangadharappa, H V; Hani, Umme; Ali M Osmani, Riyaz; Vaghela, Rudra; Kulkarni, P K; Koganti, Venkata Sairam

2017-01-01

Prostate cancer (PC) is a prostate gland cells carcinoma, the foremost reason of cancer deaths in men in developed countries, representing most common malignancy in adult males. The key obstacle to achieve practicable therapeutic effect of active drugs and capable hopeful agents including proteins and peptides, and nucleic acid for prostate cancer is the scarcity of targeted drug delivery to cells of prostate cancer. As a result, need for novel systems, strategies or therapeutic approaches to enhance the assortment of active agents meant for prostate cancer becomes an important criterion. Currently cancer research focuses on improving treatment of prostate cancer using various novel drug delivery systems of chemotherapeutic agents. These novel drug delivery systems comprise nanoparticles and liposomes. Also, strategies or therapeutic approaches intended for the prostate cancer include radiation therapy for localized prostate cancer, hormonal therapy for suppressing tumor growth, and gene-and-immunologic therapy. These systems and approaches can deliver the drugs to their selected or targeted cancer cells for the drug release in cancer atmosphere of prostate thereby enhancing the effectiveness of tumor penetration. The objective was to collect and report the recent research findings to manage the PC. Present review encloses existing diverse novel drug delivery systems and approaches intended for the management of PC. The reported miscellaneous novel drug delivery systems along with the diverse therapies are seem to be precise, secure and relatively effective; and in consequence could lead to a new track for obliteration of prostate cancer. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The gene expression program of prostate fibroblast senescence modulates neoplastic epithelial cell proliferation through paracrine mechanisms.

PubMed

Bavik, Claes; Coleman, Ilsa; Dean, James P; Knudsen, Beatrice; Plymate, Steven; Nelson, Peter S

2006-01-15

The greatest risk factor for developing carcinoma of the prostate is advanced age. Potential molecular and physiologic contributors to the frequency of cancer occurrence in older individuals include the accumulation of somatic mutations through defects in genome maintenance, epigenetic gene silencing, oxidative stress, loss of immune surveillance, telomere dysfunction, chronic inflammation, and alterations in tissue microenvironment. In this context, the process of prostate carcinogenesis can be influenced through interactions between intrinsic cellular alterations and the extrinsic microenvironment and macroenvironment, both of which change substantially as a consequence of aging. In this study, we sought to characterize the molecular alterations that occur during the process of prostate fibroblast senescence to identify factors in the aged tissue microenvironment capable of promoting the proliferation and potentially the neoplastic progression of prostate epithelium. We evaluated three mechanisms leading to cell senescence: oxidative stress, DNA damage, and replicative exhaustion. We identified a consistent program of gene expression that includes a subset of paracrine factors capable of influencing adjacent prostate epithelial growth. Both direct coculture and conditioned medium from senescent prostate fibroblasts stimulated epithelial cell proliferation, 3-fold and 2-fold, respectively. The paracrine-acting proteins fibroblast growth factor 7, hepatocyte growth factor, and amphiregulin (AREG) were elevated in the extracellular environment of senescent prostate fibroblasts. Exogenous AREG alone stimulated prostate epithelial cell growth, and neutralizing antibodies and small interfering RNA targeting AREG attenuated, but did not completely abrogate the growth-promoting effects of senescent fibroblast conditioned medium. These results support the concept that aging-related changes in the prostate microenvironment may contribute to the progression of prostate neoplasia.

STEAP: A prostate-specific cell-surface antigen highly expressed in human prostate tumors

PubMed Central

Hubert, Rene S.; Vivanco, Igor; Chen, Emily; Rastegar, Shiva; Leong, Kahan; Mitchell, Steve C.; Madraswala, Rashida; Zhou, Yanhong; Kuo, James; Raitano, Arthur B.; Jakobovits, Aya; Saffran, Douglas C.; Afar, Daniel E. H.

1999-01-01

In search of novel genes expressed in metastatic prostate cancer, we subtracted cDNA isolated from benign prostatic hypertrophic tissue from cDNA isolated from a prostate cancer xenograft model that mimics advanced disease. One novel gene that is highly expressed in advanced prostate cancer encodes a 339-amino acid protein with six potential membrane-spanning regions flanked by hydrophilic amino- and carboxyl-terminal domains. This structure suggests a potential function as a channel or transporter protein. This gene, named STEAP for six-transmembrane epithelial antigen of the prostate, is expressed predominantly in human prostate tissue and is up-regulated in multiple cancer cell lines, including prostate, bladder, colon, ovarian, and Ewing sarcoma. Immunohistochemical analysis of clinical specimens demonstrates significant STEAP expression at the cell–cell junctions of the secretory epithelium of prostate and prostate cancer cells. Little to no staining was detected at the plasma membranes of normal, nonprostate human tissues, except for bladder tissue, which expressed low levels of STEAP at the cell membrane. Protein analysis located STEAP at the cell surface of prostate-cancer cell lines. Our results support STEAP as a cell-surface tumor-antigen target for prostate cancer therapy and diagnostic imaging. PMID:10588738

Prostate-Specific Antigen and Prostate-Specific Antigen Velocity as Threshold Indicators in 11C-Acetate PET/CTAC Scanning for Prostate Cancer Recurrence

PubMed Central

Dusing, Reginald W.; Peng, Warner; Lai, Sue-Min; Grado, Gordon L.; Holzbeierlein, Jeffrey M.; Thrasher, J. Brantley; Hill, Jacqueline; Van Veldhuizen, Peter J.

2014-01-01

Purpose The aim of this study was to identify which patient characteristics are associated with the highest likelihood of positive findings on 11C-acetate PET/computed tomography attenuation correction (CTAC) (PET/CTAC) scan when imaging for recurrent prostate cancer. Methods From 2007 to 2011, 250 11C-acetate PET/CTAC scans were performed at a single institution on patients with prostate cancer recurrence after surgery, brachytherapy, or external beam radiation. Of these patients, 120 met our inclusion criteria. Logistic regression analysis was used to examine the relationship between predictability of positive findings and patients’ characteristics, such as prostate-specific antigen (PSA) level at the time of scan, PSA kinetics, Gleason score, staging, and type of treatment before scan. Results In total, 68.3% of the 120 11C-acetate PET/CTAC scans were positive. The percentage of positive scans and PSA at the time of scanning and PSA velocity (PSAV) had positive correlations. The putative sensitivity and specificity were 86.6% and 65.8%, respectively, when a PSA level greater than 1.24 ng/mL was used as the threshold for scanning. The putative sensitivity and specificity were 74% and 75%, respectively, when a PSAV level greater than 1.32 ng/mL/y was used as the threshold. No significant associations were found between scan positivity and age, PSA doubling time, Gleason score, staging, or type of treatment before scanning. Conclusions This retrospective study suggests that threshold models of PSA greater than 1.24 ng/mL or PSAV greater than 1.32 ng/mL per year are independent predictors of positive findings in 11C-acetate PET/CTAC imaging of recurrent prostate cancer. PMID:25036021

Prostate-specific antigen lowering effect of metabolic syndrome is influenced by prostate volume.

PubMed

Choi, Woo Suk; Heo, Nam Ju; Paick, Jae-Seung; Son, Hwancheol

2016-04-01

To investigate the influence of metabolic syndrome on prostate-specific antigen levels by considering prostate volume and plasma volume. We retrospectively analyzed 4111 men who underwent routine check-ups including prostate-specific antigen and transrectal ultrasonography. The definition of metabolic syndrome was based on the modified Adult Treatment Panel III criteria. Prostate-specific antigen mass density (prostate-specific antigen × plasma volume / prostate volume) was calculated for adjusting plasma volume and prostate volume. We compared prostate-specific antigen and prostate-specific antigen mass density levels of participants with metabolic syndrome (metabolic syndrome group, n = 1242) and without metabolic syndrome (non-prostate-specific antigen metabolic syndrome group, n = 2869). To evaluate the impact of metabolic syndrome on prostate-specific antigen, linear regression analysis for the natural logarithm of prostate-specific antigen was used. Patients in the metabolic syndrome group had significantly older age (P < 0.001), larger prostate volume (P < 0.001), higher plasma volume (P < 0.001) and lower mean serum prostate-specific antigen (non-metabolic syndrome group vs metabolic syndrome group; 1.22 ± 0.91 vs 1.15 ± 0.76 ng/mL, P = 0.006). Prostate-specific antigen mass density in the metabolic syndrome group was still significantly lower than that in the metabolic syndrome group (0.124 ± 0.084 vs 0.115 ± 0.071 μg/mL, P = 0.001). After adjusting for age, prostate volume and plasma volume using linear regression model, the presence of metabolic syndrome was a significant independent factor for lower prostate-specific antigen (prostate-specific antigen decrease by 4.1%, P = 0.046). Prostate-specific antigen levels in patients with metabolic syndrome seem to be lower, and this finding might be affected by the prostate volume. © 2016 The Japanese Urological Association.

Long term organ culture of human prostate tissue in a NASA-designed rotating wall bioreactor

NASA Technical Reports Server (NTRS)

Margolis, L.; Hatfill, S.; Chuaqui, R.; Vocke, C.; Emmert-Buck, M.; Linehan, W. M.; Duray, P. H.

1999-01-01

PURPOSE: To maintain ex vivo integral prostatic tissue including intact stromal and ductal elements using the NASA-designed Rotating Wall Vessel (RWV) which maintains colocalized cells in an environment that promotes both three-dimensional cellular interactions together with the uniform mass transfer of nutrients and metabolic wastes. MATERIALS AND METHODS: Samples of normal prostate were obtained as a byproduct of transurethral prostatectomy or needle biopsy. Prostatic tissue dissected into small 1 x 1 mm. blocks was cultured in the Rotating Wall Vessel (RWV) Bioreactor for various time periods and analyzed using histological, immunochemical, and total cell RNA assays. RESULTS: We report the long term maintenance of benign explanted human prostate tissue grown in simple culture medium, under the simulated microgravity conditions afforded by the RWV bioreactor. Mesenchymal stromal elements including blood vessels and architecturally preserved tubuloglandular acini were maintained for a minimum of 28 days. Cytokeratins, vimentin and TGF-beta2 receptor and ligand were preserved through the entire culture period as revealed by immunocytochemistry. Prostatic acid phosphatase (PAP) was continuously expressed during the culture period, although somewhat decreased. Prostatic specific antigen (PSA) and its transcript were down regulated over time of culture. Prostatic carcinoma cells from the TSU cell line were able to invade RWV-cultured benign prostate tissue explants. CONCLUSIONS: The RWV bioreactor represents an additional new technology for culturing prostate tissue for further investigations concerning the basic physiology and pathobiology of this clinically important tissue.

Comparative analysis of the effect of prostatic invasion patterns on cancer-specific mortality after radical cystectomy in pT4a urothelial carcinoma of the bladder.

PubMed

Vallo, Stefan; Gilfrich, Christian; Burger, Maximilian; Volkmer, Björn; Boehm, Katharina; Rink, Michael; Chun, Felix K; Roghmann, Florian; Novotny, Vladimir; Mani, Jens; Brisuda, Antonin; Mayr, Roman; Stredele, Regina; Noldus, Joachim; Schnabel, Marco; May, Matthias; Fritsche, Hans-Martin; Pycha, Armin; Martini, Thomas; Wirth, Manfred; Roigas, Jan; Bastian, Patrick J; Nuhn, Philipp; Dahlem, Roland; Haferkamp, Axel; Fisch, Margit; Aziz, Atiqullah

2016-10-01

To evaluate the prognostic relevance of different prostatic invasion patterns in pT4a urothelial carcinoma of the bladder (UCB) after radical cystectomy. Our study comprised a total of 358 men with pT4a UCB. Patients were divided in 2 groups-group A with stromal infiltration of the prostate via the prostatic urethra with additional muscle-invasive UCB (n = 121, 33.8%) and group B with continuous infiltration of the prostate through the entire bladder wall (n = 237, 66.2%). The effect of age, tumor grade, carcinoma in situ, lymphovascular invasion, soft tissue surgical margin, lymph node metastases, administration of adjuvant chemotherapy, and prostatic invasion patterns on cancer-specific mortality (CSM) was evaluated using competing-risk regression analysis. Decision curve analysis was used to evaluate the net benefit of including the variable invasion pattern within our model. The estimated 5-year CSM-rates for group A and B were 50.1% and 66.0%, respectively. In multivariable competing-risk analysis, lymph node metastases (hazard ratio [HR] = 1.73, P<0.001), lymphovascular invasion (HR = 1.62, P = 0.0023), soft tissue surgical margin (HR = 1.49, P = 0.026), absence of adjuvant chemotherapy (HR = 2.11, P<0.001), and tumor infiltration of the prostate by continuous infiltration of the entire bladder wall (HR = 1.37, P = 0.044) were significantly associated with a higher risk for CSM. Decision curve analysis showed a net benefit of our model including the variable invasion pattern. Continuous infiltration of the prostate through the entire bladder wall showed an adverse effect on CSM. Besides including these patients into clinical trials for an adjuvant therapy, we recommend including prostatic invasion patterns in predictive models in pT4a UCB in men. Copyright © 2016 Elsevier Inc. All rights reserved.

Perceptions of Radiation Oncologists and Urologists on Sources and Type of Evidence to Inform Prostate Cancer Treatment Decisions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, Leona C.; Delpe, Sophia; Shah, Nilay D.

2014-06-01

Purpose: To perform a national survey of radiation oncologists and urologists about the type of resources used and the level of evidence needed to change clinical practice in localized prostate cancer. Methods and Materials: From a random sample, 1422 physicians were mailed a survey assessing the types of information used and what level of evidence could alter their clinical practice in prostate cancer. Multivariable logistic regression models were used to identify differences in physician characteristics for each outcome. Results: Survey response rates were similar for radiation oncologists and urologists (44% vs 46%; P=.46). Specialty-specific journals represented the most commonly usedmore » resource for informing the clinical practice for radiation oncologists (65%) and urologists (70%). Relative to radiation oncologists, urologists were less likely to report utilizing top-tier medical journals (25% vs 39%; adjusted odds ratio [OR] 0.50; P=.01) or cancer journals (22% vs 51%; adjusted OR 0.50; P<.001) but more likely to rely on clinical guidelines (46% vs 38%; adjusted OR 1.6; P=.006). Both radiation oncologists and urologists most commonly reported large randomized, clinical trials as the level of evidence to change treatment recommendations for localized prostate cancer (85% vs 77%; P=.009). Conclusions: Both specialties rely on their own specialty-specific journals and view randomized, clinical trials as the level of evidence needed to change clinical practice. Our study provides a context on meaningful ways of disseminating evidence for localized prostate cancer.« less

Recent developments in tissue-type imaging (TTI) for planning and monitoring treatment of prostate cancer.

PubMed

Feleppa, Ernest J; Porter, Christopher R; Ketterling, Jeffrey; Lee, Paul; Dasgupta, Shreedevi; Urban, Stella; Kalisz, Andrew

2004-07-01

Because current methods of imaging prostate cancer are inadequate, biopsies cannot be effectively guided and treatment cannot be effectively planned and targeted. Therefore, our research is aimed at ultrasonically characterizing cancerous prostate tissue so that we can image it more effectively and thereby provide improved means of detecting, treating and monitoring prostate cancer. We base our characterization methods on spectrum analysis of radiofrequency (rf) echo signals combined with clinical variables such as prostate-specific antigen (PSA). Tissue typing using these parameters is performed by artificial neural networks. We employed and evaluated different approaches to data partitioning into training, validation, and test sets and different neural network configuration options. In this manner, we sought to determine what neural network configuration is optimal for these data and also to assess possible bias that might exist due to correlations among different data entries among the data for a given patient. The classification efficacy of each neural network configuration and data-partitioning method was measured using relative-operating-characteristic (ROC) methods. Neural network classification based on spectral parameters combined with clinical data generally produced ROC-curve areas of 0.80 compared to curve areas of 0.64 for conventional transrectal ultrasound imaging combined with clinical data. We then used the optimal neural network configuration to generate lookup tables that translate local spectral parameter values and global clinical-variable values into pixel values in tissue-type images (TTIs). TTIs continue to show cancerous regions successfully, and may prove to be particularly useful clinically in combination with other ultrasonic and nonultrasonic methods, e.g., magnetic-resonance spectroscopy.

Recent Developments in Tissue-type Imaging(TTI) for Planning and Monitoring Treatment of Prostate Cancer

PubMed Central

Feleppa, Ernest J.; Porter, Christopher R.; Ketterling, Jeffrey; Lee, Paul; Dasgupta, Shreedevi; Urban, Stella; Kalisz, Andrew

2006-01-01

Because current methods of imaging prostate cancer are inadequate, biopsies cannot be effectively guided and treatment cannot be effectively planned and targeted. Therefore, our research is aimed at ultrasonically characterizing cancerous prostate tissue so that we can image it more effectively and thereby provide improved means of detecting, treating and monitoring prostate cancer. We base our characterization methods on spectrum analysis of radio frequency (rf) echo signals combined with clinical variables such as prostate-specific antigen (PSA). Tissue typing using these parameters is performed by artificial neural networks. We employedand evaluated different approaches to data partitioning into training, validation, and test sets and different neural network configuration options. In this manner, we sought to determine what neural network configuration is optimal for these data and also to assess possible bias that might exist due to correlations among different data entries among the data for a given patient. The classification efficacy of each neural network configuration and data-partitioning method was measured using relative-operating-characteristic (ROC) methods. Neural network classification based on spectral parameters combined with clinical data generally produced ROC-curve areas of 0.80 compared to curve areas of 0.64 for conventional transrectal ultrasound imaging combined with clinical data. We then used the optimal neural network configuration to generate lookup tables that translate local spectral parameter values and global clinical-variable values into pixel values in tissue-type images (TTIs). TTIs continue to show can cerous regions successfully, and may prove to be particularly useful clinically in combination with other ultrasonic and nonultrasonic methods, e.g., magnetic-resonance spectroscopy. PMID:15754797

Diagnostic performance of a computer-assisted diagnosis system for bone scintigraphy of newly developed skeletal metastasis in prostate cancer patients: search for low-sensitivity subgroups.

PubMed

Koizumi, Mitsuru; Motegi, Kazuki; Koyama, Masamichi; Terauchi, Takashi; Yuasa, Takeshi; Yonese, Junji

2017-08-01

The computer-assisted diagnostic system for bone scintigraphy (BS) BONENAVI is used to evaluate skeletal metastasis. We investigated its diagnostic performance in prostate cancer patients with and without skeletal metastasis and searched for the problems. An artificial neural network (ANN) value was calculated in 226 prostate cancer patients (124 with skeletal metastasis and 101 without) using BS. Receiver operating characteristic curve analysis was performed and the sensitivity and specificity determined (cutoff ANN = 0.5). Patient's situation at the time of diagnosis of skeletal metastasis, computed tomography (CT) type, extent of disease (EOD), and BS uptake grade were analyzed. False-negative and false-positive results were recorded. BONENAVI showed 82% (102/124) of sensitivity and 83% (84/101) specificity for metastasis detection. There were no significant differences among CT types, although low EOD and faint BS uptake were associated with low ANN values and low sensitivity. Patients showed lower sensitivity during the follow-up period than staging work-up. False-negative lesions were often located in the pelvis or adjacent to it. They comprised not only solitary, faint BS lesions but also overlaying to urinary excretion. BONENAVI with BS has good sensitivity and specificity for detecting prostate cancer's osseous metastasis. Low EOD and faint BS uptake are associated with low sensitivity but not the CT type. Prostate cancer patients likely to have false-negative results during the follow-up period had a solitary lesion in the pelvis with faint BS uptake or lesions overlaying to urinary excretion.

Expression of potential target antigens for immunotherapy on primary and metastatic prostate cancers.

PubMed

Zhang, S; Zhang, H S; Reuter, V E; Slovin, S F; Scher, H I; Livingston, P O

1998-02-01

Defining the expression of tumor-associated antigens on primary and metastatic prostate cancer is the crucial first step in selecting appropriate targets for immune attack. In this study, the distribution of the tumor-associated antigens GM2, Tn, sTn, Thompson-Friedenreich antigen (TF), Globo H, Le(y), MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, MUC7, carcinoembryonic antigen, beta chain of human chorionic gonadotropin (hCG beta), HER2/neu, PSMA, and KSA on primary and metastatic prostate cancer and 16 types of normal tissues was compared by immunohistochemistry, using a panel of well-characterized monoclonal antibodies. Our results show that GM2, KSA, and MUC2 were strongly expressed on 8 or 9 of 9 metastatic prostate cancer biopsy specimens and, with PSMA, hCG beta, TF, Tn, and sTn, on 8 or more of 11 primary prostate cancer specimens. Tn, MUC1, and PSMA were expressed on 4-6 of 9 metastatic specimens. The remaining antigens were expressed on no more than three of nine metastatic specimens. Normal tissues were also tested with all antibodies. With regard to the eight antigens most widely expressed on prostate cancers, PSMA was not expressed significantly on any of the normal tissues except prostate epithelium. Tn, sTn, hCG beta, and MUC2 were detected on up to 3 of 10 types of normal epithelia. GM2, TF, MUC1, and KSA were more broadly distributed on normal epithelia, all primarily at the secretory borders. STn, KSA, and hCG beta were also detected in the testis, and GM2 was expressed on gray matter of brain. From the 30 antigens that we have screened, this study provides the basis for selecting GM2, TF, Tn, sTn, hCG beta, MUC1, MUC2, KSA, and PSMA as target antigens for specific immunotherapy of prostate cancer.

Dietary tomato and lycopene impact androgen signaling- and carcinogenesis-related gene expression during early TRAMP prostate carcinogenesis

PubMed Central

Wan, Lei; Tan, Hsueh-Li; Thomas-Ahner, Jennifer M.; Pearl, Dennis K.; Erdman, John W.; Moran, Nancy E.; Clinton, Steven K.

2014-01-01

Consumption of tomato products containing the carotenoid lycopene is associated with a reduced risk of prostate cancer. To identify gene expression patterns associated with early testosterone-driven prostate carcinogenesis, which are impacted by dietary tomato and lycopene, wild type (WT) and transgenic adenocarcinoma of the mouse prostate (TRAMP) mice were fed control or tomato- or lycopene-containing diets from 4-10 wk-of-age. Eight-week-old mice underwent sham surgery, castration, or castration followed by testosterone-repletion (2.5 mg/kg/d initiated 1 wk after castration). Ten-wk-old intact TRAMP mice exhibit early multifocal prostatic intraepithelial neoplasia (PIN). Of the 200 prostate cancer-related genes measured by quantitative NanoString®, 189 are detectable, 164 significantly differ by genotype, 179 by testosterone status, and 30 by diet type (P<0.05). In TRAMP, expression of Birc5, Mki67, Aurkb, Ccnb2, Foxm1, and Ccne2 is greater compared to WT and is decreased by castration. In parallel, castration reduces Ki67-positive staining (P<0.0001) compared to intact and testosterone-repleted TRAMP mice. Expression of genes involved in androgen metabolism/signaling pathways are reduced by lycopene feeding (Srd5a1) and by tomato-feeding (Srd5a2, Pxn, and Srebf1). Additionally, tomato-feeding significantly reduced expression of genes associated with stem cell features, Aldh1a and Ly6a, while lycopene-feeding significantly reduced expression of neuroendocrine differentiation-related genes, Ngfr and Syp. Collectively, these studies demonstrate a profile of testosterone-regulated genes associated with early stages of prostate carcinogenesis that are potential mechanistic targets of dietary tomato components. Future studies on androgen signaling/metabolism, stem cell features, and neuroendocrine differentiation pathways may elucidate the mechanisms by which dietary tomato and lycopene impact prostate cancer risk. PMID:25315431

Dissecting the roles of the androgen receptor in prostate cancer from molecular perspectives.

PubMed

Hu, Jieping; Wang, Gongxian; Sun, Ting

2017-05-01

Androgen receptor plays a pivotal role in prostate cancer progression, and androgen deprivation therapy to intercept androgen receptor signal pathway is an indispensable treatment for most advanced prostate cancer patients to delay cancer progression. However, the emerging of castration-resistant prostate cancer reminds us the alteration of androgen receptor, which includes androgen receptor mutation, the formation of androgen receptor variants, and androgen receptor distribution in cancer cells. In this review, we introduce the process of androgen receptor and also its variants' formation, translocation, and function alteration by protein modification or interaction with other pathways. We dissect the roles of androgen receptor in prostate cancer from molecular perspective to provide clues for battling prostate cancer, especially castration-resistant prostate cancer.

Recent Advances in Prostate Cancer Treatment and Drug Discovery.

PubMed

Nevedomskaya, Ekaterina; Baumgart, Simon J; Haendler, Bernard

2018-05-04

Novel drugs, drug sequences and combinations have improved the outcome of prostate cancer in recent years. The latest approvals include abiraterone acetate, enzalutamide and apalutamide which target androgen receptor (AR) signaling, radium-223 dichloride for reduction of bone metastases, sipuleucel-T immunotherapy and taxane-based chemotherapy. Adding abiraterone acetate to androgen deprivation therapy (ADT) in order to achieve complete androgen blockade has proven highly beneficial for treatment of locally advanced prostate cancer and metastatic hormone-sensitive prostate cancer (mHSPC). Also, ADT together with docetaxel treatment showed significant benefit in mHSPC. Ongoing clinical trials for different subgroups of prostate cancer patients include the evaluation of the second-generation AR antagonists enzalutamide, apalutamide and darolutamide, of inhibitors of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) pathway, of inhibitors of DNA damage response, of targeted alpha therapy and of prostate-specific membrane antigen (PSMA) targeting approaches. Advanced clinical studies with immune checkpoint inhibitors have shown limited benefits in prostate cancer and more trials are needed to demonstrate efficacy. The identification of improved, personalized treatments will be much supported by the major progress recently made in the molecular characterization of early- and late-stage prostate cancer using “omics” technologies. This has already led to novel classifications of prostate tumors based on gene expression profiles and mutation status, and should greatly help in the choice of novel targeted therapies best tailored to the needs of patients.

Proteinase-Activated Receptor-1 and Immunomodulatory Effects of a PAR1-Activating Peptide in a Mouse Model of Prostatitis

PubMed Central

Stanton, M. Mark; Nelson, Lisa K.; Benediktsson, Hallgrimur; Hollenberg, Morley D.; Buret, Andre G.; Ceri, Howard

2013-01-01

Background. Nonbacterial prostatitis has no established etiology. We hypothesized that proteinase-activated receptor-1 (PAR1) can play a role in prostatitis. We therefore investigated the effects of PAR1 stimulation in the context of a new model of murine nonbacterial prostatitis. Methods. Using a hapten (ethanol-dinitrobenzene sulfonic acid- (DNBS-)) induced prostatitis model with both wild-type and PAR1-null mice, we examined (1) the location of PAR1 in the mouse prostate and (2) the impact of a PAR1-activating peptide (TFLLR-NH2: PAR1-TF) on ethanol-DNBS-induced inflammation. Results. Ethanol-DNBS-induced inflammation was maximal at 2 days. In the tissue, PAR1 was expressed predominantly along the apical acini of prostatic epithelium. Although PAR1-TF on its own did not cause inflammation, its coadministration with ethanol-DNBS reduced all indices of acute prostatitis. Further, PAR1-TF administration doubled the prostatic production of interleukin-10 (IL-10) compared with ethanol-DNBS treatment alone. This enhanced IL-10 was not observed in PAR1-null mice and was not caused by the reverse-sequence receptor-inactive peptide, RLLFT-NH2. Surprisingly, PAR1-TF, also diminished ethanol-DNBS-induced inflammation in PAR1-null mice. Conclusions. PAR1 is expressed in the mouse prostate and its activation by PAR1-TF elicits immunomodulatory effects during ethanol-DNBS-induced prostatitis. However, PAR1-TF also diminishes ethanol-DNBS-induced inflammation via a non-PAR1 mechanism by activating an as-yet unknown receptor. PMID:24459330

TLR7 expression is decreased during tumour progression in transgenic adenocarcinoma of mouse prostate mice and its activation inhibits growth of prostate cancer cells.

PubMed

Han, Ju-Hee; Park, Shin-Young; Kim, Jin-Bum; Cho, Sung-Dae; Kim, Bumseok; Kim, Bo-Yeon; Kang, Min-Jung; Kim, Dong-Jae; Park, Jae-Hak; Park, Jong-Hwan

2013-10-01

Although various Toll-like receptors (TLRs) have been associated with immune response and tumorigenesis in the prostate cells, little is known about the role of TLR7. Accordingly, we examined the expression of TLR7 during tumour progression of TRMAP (transgenic mouse model for prostate cancer) mice and its role on cell growth. Toll-like receptor7 expression was examined by RT-polymerase chain reaction (PCR), Western blot, and immunohistochemistry. Cell growth was examined by MTT assay. Colony formation was investigated by crystal violet staining. Strong expression of TLR7 was detected in the normal prostate epithelia of Wild-type (WT) mice, but not in TLR7-deficient mice. In contrast, TLR7 expression was weak in transgenic adenocarcinoma of mouse prostate (TRAMP)-C2 cells, as compared with murine bone marrow-derived macrophages (BMDMs). Moreover, TLR7 mRNA was markedly expressed in RWPE-1 cells (non-cancerous prostate epithelial cells), but not in PC3 and DU145 (prostate cancer cells). Immunohistochemically, TLR7 expression gradually decreased in TRAMP mice depending on the pathologic grade of the prostate cells. TLR7 agonists increased both the gene and protein expression of TLR7 and promoted production of proinflammatory cytokines/chemokines and IFN-β gene expression in prostate cancer cell lines. Moreover, loxoribine inhibited the growth and colony formation of TRAMP-C2 cells dependent of TLR7. These findings suggest that TLR7 may participate in tumour suppression in the prostate cells. © 2013 John Wiley & Sons Ltd.

Immortalization of human prostate epithelial cells by HPV 16 E6/E7 open reading frames.

PubMed

Choo, C K; Ling, M T; Chan, K W; Tsao, S W; Zheng, Z; Zhang, D; Chan, L C; Wong, Y C

1999-08-01

The exact pathogenesis for prostate cancer is not known. Progress made in prostate cancer research has been slow, largely due to the lack of suitable in vitro models. Here, we report our work on the immortalization of a human prostate epithelial cell line and show that it can be used as a model to study prostate tumorigenesis. Replication-defective retrovirus harboring the human papillomavirus (HPV) type 16 E6 and E7 open reading frames was used to infect primary human prostate epithelial cells. Polymerase chain reaction, followed by Southern hybridization for the HPV 16 E6/E7, Western blot for prostatic acid phosphatase, telomeric repeat amplification protocol assay for telomerase activity, two-dimensional gels for cytokeratins, and cytogenetic analysis were undertaken to characterized the infected cells. The retrovirus-infected cell line, HPr-1, continued to grow in culture for more than 80 successive passages. Normal primary cells failed to proliferate after passage 6. HPr-1 cells bore close resemblance to normal primary prostate epithelial cells, both morphologically and biochemically. However, they possessed telomerase activity and proliferated indefinitely. Cytogenetic analysis of HPr-1 cells revealed a human male karyotype with clonal abnormalities and the appearance of multiple double minutes. The HPr-1 cells expressed prostatic acid phosphatase and cytokeratins K8 and K18, proving that they were prostate epithelial cells. They were benign in nude mice tumor formation and soft agar colony formation assay. The HPr-1 cell line is an in vitro representation of early prostate neoplastic progression. Copyright 1999 Wiley-Liss, Inc.

The emerging role of obesity, diet and lipid metabolism in prostate cancer.

PubMed

Ferro, Matteo; Terracciano, Daniela; Buonerba, Carlo; Lucarelli, Giuseppe; Bottero, Danilo; Perdonà, Sisto; Autorino, Riccardo; Serino, Alessandro; Cantiello, Francesco; Damiano, Rocco; Andras, Iulia; De Placido, Sabino; Di Lorenzo, Giuseppe; Battaglia, Michele; Jereczek-Fossa, Barbara A; Mirone, Vincenzo; De Cobelli, Ottavio

2017-02-01

Obesity is associated with an increased risk of a number of serious medical conditions, including cancer. As far as prostate cancer is concerned, obesity is associated with an increased risk of high-grade tumors, which is possibly related to lower androgen levels. Diet may also affect prostate cancer risk since countries with a higher dietary fat intake also present higher prostate cancer mortality rates. Interestingly, prostate cancer is associated with a number of metabolic alterations that may provide valuable diagnostic and therapeutic targets. This review explores the available clinical as well as biological evidence supporting the relationship between obesity, diet, alteration in metabolic pathways and prostate cancer.

A panel of kallikrein markers can reduce unnecessary biopsy for prostate cancer: data from the European Randomized Study of Prostate Cancer Screening in Göteborg, Sweden

PubMed Central

Vickers, Andrew J; Cronin, Angel M; Aus, Gunnar; Pihl, Carl-Gustav; Becker, Charlotte; Pettersson, Kim; Scardino, Peter T; Hugosson, Jonas; Lilja, Hans

2008-01-01

Background Prostate-specific antigen (PSA) is widely used to detect prostate cancer. The low positive predictive value of elevated PSA results in large numbers of unnecessary prostate biopsies. We set out to determine whether a multivariable model including four kallikrein forms (total, free, and intact PSA, and human kallikrein 2 (hK2)) could predict prostate biopsy outcome in previously unscreened men with elevated total PSA. Methods The study cohort comprised 740 men in Göteborg, Sweden, undergoing biopsy during the first round of the European Randomized study of Screening for Prostate Cancer. We calculated the area-under-the-curve (AUC) for predicting prostate cancer at biopsy. AUCs for a model including age and PSA (the 'laboratory' model) and age, PSA and digital rectal exam (the 'clinical' model) were compared with those for models that also included additional kallikreins. Results Addition of free and intact PSA and hK2 improved AUC from 0.68 to 0.83 and from 0.72 to 0.84, for the laboratory and clinical models respectively. Using a 20% risk of prostate cancer as the threshold for biopsy would have reduced the number of biopsies by 424 (57%) and missed only 31 out of 152 low-grade and 3 out of 40 high-grade cancers. Conclusion Multiple kallikrein forms measured in blood can predict the result of biopsy in previously unscreened men with elevated PSA. A multivariable model can determine which men should be advised to undergo biopsy and which might be advised to continue screening, but defer biopsy until there was stronger evidence of malignancy. PMID:18611265

Portfolio of prospective clinical trials including brachytherapy: an analysis of the ClinicalTrials.gov database.

PubMed

Cihoric, Nikola; Tsikkinis, Alexandros; Miguelez, Cristina Gutierrez; Strnad, Vratislav; Soldatovic, Ivan; Ghadjar, Pirus; Jeremic, Branislav; Dal Pra, Alan; Aebersold, Daniel M; Lössl, Kristina

2016-03-22

To evaluate the current status of prospective interventional clinical trials that includes brachytherapy (BT) procedures. The records of 175,538 (100 %) clinical trials registered at ClinicalTrials.gov were downloaded on September 2014 and a database was established. Trials using BT as an intervention were identified for further analyses. The selected trials were manually categorized according to indication(s), BT source, applied dose rate, primary sponsor type, location, protocol initiator and funding source. We analyzed trials across 8 available trial protocol elements registered within the database. In total 245 clinical trials were identified, 147 with BT as primary investigated treatment modality and 98 that included BT as an optional treatment component or as part of the standard treatment. Academic centers were the most frequent protocol initiators in trials where BT was the primary investigational treatment modality (p < 0.01). High dose rate (HDR) BT was the most frequently investigated type of BT dose rate (46.3 %) followed by low dose rate (LDR) (42.0 %). Prostate was the most frequently investigated tumor entity in trials with BT as the primary treatment modality (40.1 %) followed by breast cancer (17.0 %). BT was rarely the primary investigated treatment modality for cervical cancer (6.8 %). Most clinical trials using BT are predominantly in early phases, investigator-initiated and with low accrual numbers. Current investigational activities that include BT mainly focus on prostate and breast cancers. Important questions concerning the optimal usage of BT will not be answered in the near future.

Prostatic Artery Embolization (PAE) for Symptomatic Benign Prostatic Hyperplasia (BPH): Part 2, Insights into the Technical Rationale

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, Fei, E-mail: feisun@ccmijesususon.com; Crisóstomo, Verónica, E-mail: crisosto@ccmijesususon.com; Báez-Díaz, Claudia, E-mail: cbaez@ccmijesususon.com

Rationale of prostatic artery embolization (PAE) in the treatment of symptomatic benign prostatic hyperplasia is conventionally believed to include two parts: shrinkage of the enlarged prostate gland as a result of PAE-induced ischemic infarction and potential effects to relax the increased prostatic smooth muscle tone by reducing the number and density of α{sub 1}-adrenergic receptor in the prostate stroma. This review describes new insights into the likely mechanisms behind PAE, such as ischemia-induced apoptosis, apoptosis enhanced by blockage of androgens circulation to the embolized prostate, secondary denervation following PAE, and potential effect of nitric oxide pathway immediately after embolization. Studiesmore » on therapeutic mechanisms in PAE may shed light on potentially new treatment strategies and development of novel techniques.« less

Sca-1 Identifies a Distinct Androgen-Independent Murine Prostatic Luminal Cell Lineage with Bipotent Potential

PubMed Central

Kwon, Oh-Joon; Zhang, Li; Xin, Li

2016-01-01

Recent lineage tracing studies support the existence of prostate luminal progenitors that possess extensive regenerative capacity, but their identity remains unknown. We show that Sca-1 (Stem Cell Antigen-1) identifies a small population of murine prostate luminal cells that reside in the proximal prostatic ducts adjacent to the urethra. Sca-1+ luminal cells do not express Nkx3.1. They do not carry the secretory function, although they express the androgen receptor. These cells are enriched in the prostates of castrated mice. In the in vitro prostate organoid assay, a small fraction of the Sca-1+ luminal cells are capable of generating budding organoids that are morphologically distinct from those derived from other cell lineages. Histologically, this type of organoid is composed of multiple inner layers of luminal cells surrounded by multiple outer layers of basal cells. When passaged, these organoids retain their morphological and histological features. Finally, the Sca-1+ luminal cells are capable of forming small prostate glands containing both basal and luminal cells in an in vivo prostate regeneration assay. Collectively, our study establishes the androgen-independent and bipotent organoid-forming Sca-1+ luminal cells as a functionally distinct cellular entity. These cells may represent a putative luminal progenitor population and serve as a cellular origin for castration resistant prostate cancer. PMID:26418304

Cell-autonomous intracellular androgen receptor signaling drives the growth of human prostate cancer initiating cells.

PubMed

Vander Griend, Donald J; D'Antonio, Jason; Gurel, Bora; Antony, Lizamma; Demarzo, Angelo M; Isaacs, John T

2010-01-01

The lethality of prostate cancer is due to the continuous growth of cancer initiating cells (CICs) which are often stimulated by androgen receptor (AR) signaling. However, the underlying molecular mechanism(s) for such AR-mediated growth stimulation are not fully understood. Such mechanisms may involve cancer cell-dependent induction of tumor stromal cells to produce paracrine growth factors or could involve cancer cell autonomous autocrine and/or intracellular AR signaling pathways. We utilized clinical samples, animal models and a series of AR-positive human prostate cancer cell lines to evaluate AR-mediated growth stimulation of prostate CICs. The present studies document that stromal AR expression is not required for prostate cancer growth, since tumor stroma surrounding AR-positive human prostate cancer metastases (N = 127) are characteristically AR-negative. This lack of a requirement for AR expression in tumor stromal cells is also documented by the fact that human AR-positive prostate cancer cells grow equally well when xenografted in wild-type versus AR-null nude mice. AR-dependent growth stimulation was documented to involve secretion, extracellular binding, and signaling by autocrine growth factors. Orthotopic xenograft animal studies documented that the cellautonomous autocrine growth factors which stimulate prostate CIC growth are not the andromedins secreted by normal prostate stromal cells. Such cell autonomous and extracellular autocrine signaling is necessary but not sufficient for the optimal growth of prostate CICs based upon the response to anti-androgen plus/or minus preconditioned media. AR-induced growth stimulation of human prostate CICs requires AR-dependent intracellular pathways. The identification of such AR-dependent intracellular pathways offers new leads for the development of effective therapies for prostate cancer. (c) 2009 Wiley-Liss, Inc.

Serum quantitative proteomic analysis reveals potential zinc-associated biomarkers for nonbacterial prostatitis.

PubMed

Yang, Xiaoli; Li, Hongtao; Zhang, Chengdong; Lin, Zhidi; Zhang, Xinhua; Zhang, Youjie; Yu, Yanbao; Liu, Kun; Li, Muyan; Zhang, Yuening; Lv, Wenxin; Xie, Yuanliang; Lu, Zheng; Wu, Chunlei; Teng, Ruobing; Lu, Shaoming; He, Min; Mo, Zengnan

2015-10-01

Prostatitis is one of the most common urological problems afflicting adult men. The etiology and pathogenesis of nonbacterial prostatitis, which accounts for 90-95% of cases, is largely unknown. As serum proteins often indicate the overall pathologic status of patients, we hypothesized that protein biomarkers of prostatitis might be identified by comparing the serum proteomes of patients with and without nonbacterial prostatitis. All untreated samples were collected from subjects attending the Fangchenggang Area Male Health and Examination Survey (FAMHES). We profiled pooled serum samples from four carefully selected groups of patients (n = 10/group) representing the various categories of nonbacterial prostatitis (IIIa, IIIb, and IV) and matched healthy controls using a mass spectrometry-based 4-plex iTRAQ proteomic approach. More than 160 samples were validated by ELISA. Overall, 69 proteins were identified. Among them, 42, 52, and 37 proteins were identified with differential expression in Category IIIa, IIIb, and IV prostatitis, respectively. The 19 common proteins were related to immunity and defense, ion binding, transport, and proteolysis. Two zinc-binding proteins, superoxide dismutase 3 (SOD3), and carbonic anhydrase I (CA1), were significantly higher in all types of prostatitis than in the control. A receiver operating characteristic curve estimated sensitivities of 50.4 and 68.1% and specificities of 92.1 and 83.8% for CA1 and SOD3, respectively, in detecting nonbacterial prostatitis. The serum CA1 concentration was inversely correlated to the zinc concentration in expressed-prostatic secretions. Our findings suggest that SOD3 and CA1 are potential diagnostic markers of nonbacterial prostatitis, although further large-scale studies are required. The molecular profiles of nonbacterial prostatitis pathogenesis may lay a foundation for discovery of new therapies. © 2015 Wiley Periodicals, Inc.

Recommended patient-reported core set of symptoms to measure in prostate cancer treatment trials.

PubMed

Chen, Ronald C; Chang, Peter; Vetter, Richard J; Lukka, Himansu; Stokes, William A; Sanda, Martin G; Watkins-Bruner, Deborah; Reeve, Bryce B; Sandler, Howard M

2014-07-01

The National Cancer Institute (NCI) Symptom Management and Health-Related Quality of Life Steering Committee convened four working groups to recommend core sets of patient-reported outcomes to be routinely incorporated in clinical trials. The Prostate Cancer Working Group included physicians, researchers, and a patient advocate. The group's process included 1) a systematic literature review to determine the prevalence and severity of symptoms, 2) a multistakeholder meeting sponsored by the NCI to review the evidence and build consensus, and 3) a postmeeting expert panel synthesis of findings to finalize recommendations. Five domains were recommended for localized prostate cancer: urinary incontinence, urinary obstruction and irritation, bowel-related symptoms, sexual dysfunction, and hormonal symptoms. Four domains were recommended for advanced prostate cancer: pain, fatigue, mental well-being, and physical well-being. Additional domains for consideration include decisional regret, satisfaction with care, and anxiety related to prostate cancer. These recommendations have been endorsed by the NCI for implementation. © The Author 2014. Published by Oxford University Press. All rights reserved.

78 FR 57505 - World Trade Center Health Program; Addition of Prostate Cancer to the List of WTC-Related Health...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-19

.... Public Participation III. Background A. WTC Health Program Statutory Authority B. Methods Used by the... condition to the List of WTC-Related Health Conditions (List) codified in 42 CFR 88.1. B. Methods Used by... types of cancer to the List of WTC-Related Health Conditions included in 42 CFR 88.1.\\2\\ Method 1 is the...

The Role of a Novel Myosin Isoform in Prostate Cancer Metastasis

DTIC Science & Technology

2013-10-01

of unconventional myosin function and targeting, Annu. Rev. Cell Dev. Biol. 27 (2011) 133–155. [42] W. Kliche, S. Fujita- Becker , M. Kollmar, D.J...tissue-specific diseases (laminopathies), including Emery–Dreifuss muscular dystrophy , Dunnigan-type familial partial lipodystrophy (FPLD), and...structure of the C-terminal domain of lamin A/C, mutated in muscular dystrophies , cardiomyopathy, and partial lipodystrophy. Structure 10, 811–823

Prostate Stem Cell Antigen DNA Vaccination Breaks Tolerance to Self-antigen and Inhibits Prostate Cancer Growth

PubMed Central

Ahmad, Sarfraz; Casey, Garrett; Sweeney, Paul; Tangney, Mark; O'Sullivan, Gerald C

2009-01-01

Prostate stem cell antigen (PSCA) is a cell surface antigen expressed in normal human prostate and over expressed in prostate cancer. Elevated levels of PSCA protein in prostate cancer correlate with increased tumor stage/grade, with androgen independence and have higher expression in bone metastases. In this study, the PSCA gene was isolated from the transgenic adenocarcinoma mouse prostate cell line (TRAMPC1), and a vaccine plasmid construct was generated. This plasmid PSCA (pmPSCA) was delivered by intramuscular electroporation (EP) and induced effective antitumor immune responses against subcutaneous TRAMPC1 tumors in male C57 BL/6 mice. The pmPSCA vaccination inhibited tumor growth, resulting in cure or prolongation in survival. Similarly, the vaccine inhibited metastases in PSCA expressing B16 F10 tumors. There was activation of Th-1 type immunity against PSCA, indicating the breaking of tolerance to a self-antigen. This immunity was tumor specific and was transferable by adoptive transfer of splenocytes. The mice remained healthy and there was no evidence of collateral autoimmune responses in normal tissues. EP-assisted delivery of the pmPSCA evoked strong specific responses and could, in neoadjuvant or adjuvant settings, provide a safe and effective immune control of prostate cancer, given that there is significant homology between human and mouse PSCA. PMID:19337234

Autonomic nerve development contributes to prostate cancer progression.

PubMed

Magnon, Claire; Hall, Simon J; Lin, Juan; Xue, Xiaonan; Gerber, Leah; Freedland, Stephen J; Frenette, Paul S

2013-07-12

Nerves are a common feature of the microenvironment, but their role in tumor growth and progression remains unclear. We found that the formation of autonomic nerve fibers in the prostate gland regulates prostate cancer development and dissemination in mouse models. The early phases of tumor development were prevented by chemical or surgical sympathectomy and by genetic deletion of stromal β2- and β3-adrenergic receptors. Tumors were also infiltrated by parasympathetic cholinergic fibers that promoted cancer dissemination. Cholinergic-induced tumor invasion and metastasis were inhibited by pharmacological blockade or genetic disruption of the stromal type 1 muscarinic receptor, leading to improved survival of the mice. A retrospective blinded analysis of prostate adenocarcinoma specimens from 43 patients revealed that the densities of sympathetic and parasympathetic nerve fibers in tumor and surrounding normal tissue, respectively, were associated with poor clinical outcomes. These findings may lead to novel therapeutic approaches for prostate cancer.

Prostate cancer and social media.

PubMed

Loeb, Stacy; Katz, Matthew S; Langford, Aisha; Byrne, Nataliya; Ciprut, Shannon

2018-04-11

The use of social media is increasing globally and is employed in a variety of ways in the prostate cancer community. In addition to their use in research, advocacy, and awareness campaigns, social media offer vast opportunities for education and networking for patients with prostate cancer and health-care professionals, and many educational resources and support networks are available to patients with prostate cancer and their caregivers. Despite the considerable potential for social media to be employed in the field of prostate cancer, concerns remain - particularly regarding the maintenance of patient confidentiality, variable information quality, and possible financial conflicts of interest. A number of professional societies have, therefore, issued guidance regarding social media use in medicine. Social media are used extensively in other cancer communities, particularly among patients with breast cancer, and both the quantity and type of information available are expected to grow in the future.

Testing the feasibility, acceptability and effectiveness of a 'decision navigation' intervention for early stage prostate cancer patients in Scotland--a randomised controlled trial.

PubMed

Hacking, Belinda; Wallace, Louise; Scott, Sarah; Kosmala-Anderson, Joanna; Belkora, Jeffrey; McNeill, Alan

2013-05-01

Does decision navigation (DN) increase prostate cancer patients' confidence and certainty in treatment decisions, while reducing regret associated with the decisions made? Two hundred eighty-nine newly diagnosed prostate cancer patients were eligible. 123 consented and were randomised to usual care (n = 60) or navigation (n = 63). The intervention involved a 'navigator' guiding the patient in creating a personal question list for a consultation and providing a CD and typed summary of the consultation to patients, the general practitioner and physician. The primary outcome was decisional self efficacy. Secondary outcomes included decisional conflict (DCS) and decisional regret (RS). Measures of mood (Hospital Anxiety and Depression Scale) and adjustment (Mental Adjustment to Cancer Scale) were included to detect potential adverse effects of the intervention. ANOVA showed a main effect for the group (F = 7.161, df 1, p = 0.009). Post hoc comparisons showed significantly higher decisional self efficacy in the navigated patients post-consultation and 6 months later. Decisional conflict was lower for navigated patients initially (t = 2.005, df = 105, p = 0.047), not at follow-up (t = 1.969, df = 109, p = 0.052). Regret scores were significantly lower in the navigation group compared to the controls 6 months later (t = -2.130, df = 100, p = 0.036). There was no impact of the intervention on mood or adjustment. Compared to control patients, navigated patients were more confident in making decisions about cancer treatment, were more certain they had made the right decision after the consultation and had less regret about their decision 6 months later. Decision navigation was feasible, acceptable and effective for newly diagnosed prostate cancer patients in Scotland. Copyright © 2012 John Wiley & Sons, Ltd.

Genome-wide CRISPR screen identifies HNRNPL as a prostate cancer dependency regulating RNA splicing.

PubMed

Fei, Teng; Chen, Yiwen; Xiao, Tengfei; Li, Wei; Cato, Laura; Zhang, Peng; Cotter, Maura B; Bowden, Michaela; Lis, Rosina T; Zhao, Shuang G; Wu, Qiu; Feng, Felix Y; Loda, Massimo; He, Housheng Hansen; Liu, X Shirley; Brown, Myles

2017-06-27

Alternative RNA splicing plays an important role in cancer. To determine which factors involved in RNA processing are essential in prostate cancer, we performed a genome-wide CRISPR/Cas9 knockout screen to identify the genes that are required for prostate cancer growth. Functional annotation defined a set of essential spliceosome and RNA binding protein (RBP) genes, including most notably heterogeneous nuclear ribonucleoprotein L (HNRNPL). We defined the HNRNPL-bound RNA landscape by RNA immunoprecipitation coupled with next-generation sequencing and linked these RBP-RNA interactions to changes in RNA processing. HNRNPL directly regulates the alternative splicing of a set of RNAs, including those encoding the androgen receptor, the key lineage-specific prostate cancer oncogene. HNRNPL also regulates circular RNA formation via back splicing. Importantly, both HNRNPL and its RNA targets are aberrantly expressed in human prostate tumors, supporting their clinical relevance. Collectively, our data reveal HNRNPL and its RNA clients as players in prostate cancer growth and potential therapeutic targets.

The expanding role of epigenetics in the development, diagnosis and treatment of prostate cancer and benign prostatic hyperplasia.

PubMed

Dobosy, Joseph R; Roberts, J Lea W; Fu, Vivian X; Jarrard, David F

2007-03-01

Prostate cancer research has focused significant attention on the mutation, deletion or amplification of the DNA base sequence that encodes critical growth or suppressor genes. However, these changes have left significant gaps in our understanding of the development and progression of disease. It has become clear that epigenetic changes or modifications that influence phenotype without altering the genotype present a new and entirely different mechanism for gene regulation. Several interrelated epigenetic modifications that are altered in abnormal growth states are DNA methylation changes, histone modifications and genomic imprinting. We discuss the status of epigenetic alterations in prostate cancer and benign prostatic hyperplasia progression. In addition, the rationale and status of ongoing clinical trials altering epigenetic processes in urological diseases are reviewed. An online search of current and past peer reviewed literature on DNA methylation, histone acetylation and methylation, imprinting and epigenetics in prostate cancer and benign prostatic hyperplasia was performed. Relevant articles and reviews were examined and a synopsis of reproducible data was generated with the goal of informing the practicing urologist of these advances and their implications. Only 20 years ago the first study was published demonstrating global changes in DNA methylation patterns in tumors. Accumulating data have now identified specific genes that are commonly hypermethylated and inactivated during prostate cancer progression, including GSTpi, APC, MDR1, GPX3 and 14-3-3sigma. Altered histone modifications, including acetylation and methylation, were also recently described that may modify gene function, including androgen receptor function. These epigenetic changes are now being used to assist in prostate cancer diagnosis and cancer outcome prediction. Epigenetic changes appear to have a role in benign prostatic hyperplasia development as well as in the susceptibility of the prostate to developing cancer. Treatments involving 5-aza-deoxycytosine and other, more selective DNA methyltransferase inhibitors remove methyl residues from silenced genes, generating re-expression, and are currently being used in therapeutic trials. Histone deacetylase inhibitors have shown promise, not only by directly reactivating silenced genes, but also as regulators of apoptosis and sensitizers to radiation therapy. Evolving data support a significant role for epigenetic processes in the development of prostate cancer and benign prostatic hyperplasia. Epigenetic changes can predict tumor behavior and often distinguish between genetically identical tumors. Targeted drugs that alter epigenetic modifications hold promise as a tool for curing and preventing these diseases.

Mitochondrial β-Carotene 9',10' Oxygenase Modulates Prostate Cancer Growth via NF-κB Inhibition: A Lycopene-Independent Function.

PubMed

Gong, Xiaoming; Marisiddaiah, Raju; Zaripheh, Susan; Wiener, Doris; Rubin, Lewis P

2016-10-01

Despite numerous inquiries into protective roles of lycopene in prostate cancer prevention or therapy, little is known about mechanisms by which lycopene or its metabolites inhibit prostate cancer. The enzyme β-carotene 9',10'-oxygenase (BCO2), which catalyzes asymmetric cleavage of several carotenoids, is the principal regulator of lycopene metabolism, but the range of BCO2 biological functions is incompletely understood. This study investigated expression and functional roles of BCO2 in human prostate cancer. Expression of the bco2 gene is dramatically decreased in prostate cancer tissue and in a range of prostate cancer cell lines as compared with nonneoplastic prostate tissue and normal prostatic epithelial cells, respectively. Inhibition of DNA methyltransferase activity restored bco2 expression in prostate cancer cell lines tested. Treatment with lycopene or its metabolite, apo-10-lycopenal, also increased bco2 expression and reduced cell proliferation in androgen-sensitive cell lines, but lycopene neither altered bco2 expression nor cell growth in androgen-resistant cells. Notably, restoring bco2 expression in prostate cancer cells inhibited cell proliferation and colony formation, irrespective of lycopene exposure. Exogenous expression of either wild-type BCO2 or a mutant (enzymatically inactive) BCO2 in prostate cancer cells reduced NF-κB activity and decreased NF-κB nuclear translocation and DNA binding. Together, these results indicate epigenetic loss of BCO2 expression is associated with prostate cancer progression. Moreover, these findings describe previously unanticipated functions of BCO2 that are independent of its enzymatic role in lycopene metabolism. This study identifies BCO2 as a tumor suppressor in prostate cancer. BCO2-mediated inhibition of NF-κB signaling implies BCO2 status is important in prostate cancer progression. Mol Cancer Res; 14(10); 966-75. ©2016 AACR. ©2016 American Association for Cancer Research.

Hypoexpression and epigenetic regulation of candidate tumor suppressor gene CADM-2 in human prostate cancer.

PubMed

Chang, Guimin; Xu, Shuping; Dhir, Rajiv; Chandran, Uma; O'Keefe, Denise S; Greenberg, Norman M; Gingrich, Jeffrey R

2010-11-15

Cell adhesion molecules (CADM) comprise a newly identified protein family whose functions include cell polarity maintenance and tumor suppression. CADM-1, CADM-3, and CADM-4 have been shown to act as tumor suppressor genes in multiple cancers including prostate cancer. However, CADM-2 expression has not been determined in prostate cancer. The CADM-2 gene was cloned and characterized and its expression in human prostatic cell lines and cancer specimens was analyzed by reverse transcription-PCR and an immunohistochemical tissue array, respectively. The effects of adenovirus-mediated CADM-2 expression on prostate cancer cells were also investigated. CADM-2 promoter methylation was evaluated by bisulfite sequencing and methylation-specific PCR. We report the initial characterization of CADM-2 isoforms: CADM-2a and CADM-2b, each with separate promoters, in human chromosome 3p12.1. Prostate cancer cell lines, LNCaP and DU145, expressed negligible CADM-2a relative to primary prostate tissue and cell lines, RWPE-1 and PPC-1, whereas expression of CADM-2b was maintained. Using immunohistochemistry, tissue array results from clinical specimens showed statistically significant decreased expression in prostate carcinoma compared with normal donor prostate, benign prostatic hyperplasia, prostatic intraepithelial neoplasia, and normal tissue adjacent to tumor (P < 0.001). Adenovirus-mediated CADM-2a expression suppressed DU145 cell proliferation in vitro and colony formation in soft agar. The decrease in CADM-2a mRNA in cancer cell lines correlated with promoter region hypermethylation as determined by bisulfite sequencing and methylation-specific PCR. Accordingly, treatment of cells with the demethylating agent 5-aza-2'-deoxycytidine alone or in combination with the histone deacetylase inhibitor trichostatin A resulted in the reactivation of CADM-2a expression. CADM-2a protein expression is significantly reduced in prostate cancer. Its expression is regulated in part by promoter methylation and implicates CADM-2 as a previously unrecognized tumor suppressor gene in a proportion of human prostate cancers. ©2010 AACR.

Prostate-specific antigen velocity is not better than total prostate-specific antigen in predicting prostate biopsy diagnosis.

PubMed

Gorday, William; Sadrzadeh, Hossein; de Koning, Lawrence; Naugler, Christopher T

2015-12-01

1.) Identify whether prostate-specific antigen velocity improves the ability to predict prostate biopsy diagnosis. 2.) Test whether there is an increase in the predictive capability of models when Gleason 7 prostate cancers are separated into a 3+4 and a 4+3 group. Calgary Laboratory Services' Clinical Laboratory Information System was searched for prostate biopsies reported between January 1, 2009 and December 31, 2013. Total prostate-specific antigen tests were recorded for each patient from January 1, 2007 to the most recent test before their recorded prostate biopsy. The data set was divided into the following three groups for comparison; benign, all prostate cancer and Gleason 7-10. The Gleason grade 7-10 group was further divided into 4+3 and 3+4 Gleason 7 prostate cancers. Prostate-specific antigen velocity was calculated using four different methods found in the literature. Receiver operator curves were used to assess operational characteristics of the tests. 4622 men between the ages of 40-89 with a prostate biopsy were included for analysis. Combining prostate-specific antigen velocity with total prostate-specific antigen (AUC=0.570-0.712) resulted in small non-statistically significant changes to the area under the curve compared to the area under the curve of total prostate-specific antigen alone (AUC=0.572-0.699). There were marked increases in the area under curves when 3+4 and 4+3 Gleason 7 cancers were separated. Prostate-specific antigen velocity does not add predictive value for prostate biopsy diagnosis. The clinical significance of the prostate specific antigen test can be improved by separating Gleason 7 prostate cancers into a 3+4 and 4+3 group. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Quantification of mutant SPOP proteins in prostate cancer using mass spectrometry-based targeted proteomics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Hui; Barbieri, Christopher E.; He, Jintang

Speckle-type POZ protein (SPOP) is an E3 ubiquitin ligase adaptor protein that functions as a potential tumor suppressor, and SPOP mutations have been identified in ~10% of human prostate cancers. However, it remains unclear if mutant SPOP proteins can be utilized as biomarkers for early detection, diagnosis, prognosis or targeted therapy of prostate cancer. Moreover, the SPOP mutation sites are distributed in a relatively short region where multiple lysine residues, posing significant challenges for bottom-up proteomics analysis of the SPOP mutations. To address this issue, PRISM (high-pressure, high-resolution separations coupled with intelligent selection and multiplexing)-SRM (selected reaction monitoring) mass spectrometrymore » assays have been developed for quantifying wild-type SPOP protein and 11 prostate cancer-derived SPOP mutations. Despite inherent limitations due to amino acid sequence constraints, all the PRISM-SRM assays developed using Arg-C digestion showed a linear dynamic range of at least two orders of magnitude, with limits of quantification range from 0.1 to 1 fmol/μg of total protein in the cell lysate. Applying these SRM assays to analyze HEK293T cells with and without expression of the three most frequent SPOP mutations in prostate cancer (Y87N, F102C or F133V) led to confident detection of all three SPOP mutations in corresponding positive cell lines but not in the negative cell lines. Expression of the F133V mutation and wild-type SPOP was at much lower levels compared to that of F102C and Y87N mutations; however, at present it is unknown if this also affects the activity of the SPOP protein. In summary, PRISM-SRM enables multiplexed, isoform-specific detection of mutant SPOP proteins in cell lysates, which holds great potential in biomarker development for prostate cancer.« less

Comparison of 68Ga-PSMA PET/CT and multiparametric MRI for staging of high-risk prostate cancer68Ga-PSMA PET and MRI in prostate cancer.

PubMed

Tulsyan, Shruti; Das, Chandan J; Tripathi, Madhavi; Seth, Amlesh; Kumar, Rajeev; Bal, Chandrasekhar

2017-12-01

We carried out this study to compare Glu-NH-CO-NH-Lys-(Ahx) [Ga(HBED-CC)] [Ga prostate-specific membrane antigen-11 (PSMA-11)] PET with multiparametric MRI (mpMRI) for the staging of high-risk prostate cancer. This was a prospective study in which 36 patients with high-risk prostate cancer were included. The criteria for inclusion were biopsy-proven prostate cancer with a serum prostate specific antigen of at least 20 and/or Gleason's score of at least 8. Each patient then underwent both gallium-68 (Ga)-PSMA PET/computed tomography (CT) and mpMRI including diffusion-weighted whole-body imaging with background body signal suppression within an interval of 1 week and both modalities were compared for staging of primary disease, lymph node, and distant metastasis. The median age of the 36 patients included was 65 years (range: 44-80 years) and the median prostate specific antigen was 94.3 ng/ml (range: 20-19005  ng/ml). Concordance for localization of primary on Ga-PSMA PET/CT and MRI was observed in 19/36 (52.7%) patients. Concurrence for T staging on Ga-PSMA and MRI was observed in 58.3% of patients. Ga-PSMA PET/CT detected higher numbers of patients with regional (29) and nonregional (15) lymph nodes in comparison with MRI (20 and 5, respectively). Concurrence for regional and nonregional lymph node staging was observed in 72.2% of patients. Additional sites of metastatic disease reported on Ga-PSMA PET/CT were to the skeleton in one patient, the lung in two patients, and the liver in one patient. This study suggests that Ga-PSMA PET/CT is useful for lymph node and metastases staging in high-risk prostate cancers, whereas its utility for staging of disease in the prostate is limited.

Prostate Zonal Volumetry as a Predictor of Clinical Outcomes for Prostate Artery Embolization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Assis, André Moreira de, E-mail: andre.assis@criep.com.br, E-mail: andre.maa@gmail.com; Maciel, Macello Sampaio, E-mail: macielmjs@gmail.com; Moreira, Airton Mota, E-mail: airton.mota@criep.com.br

PurposeTo determine prostate baseline zonal volumetry and correlate these findings with clinical outcomes for patients who underwent prostate artery embolization (PAE) for lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH).Materials and MethodsThis is a retrospective study that included patients treated by PAE from 2010 to 2014. Baseline and 6-month follow-up evaluations included prostate MRI with whole prostate (WP) and central gland (CG) volume measurements—as well as prostate zonal volumetry index (ZVi) calculation, defined as the CG/WP volumes relation—the International Prostate Symptom Score (IPSS), and the Quality of life (QoL) index. Baseline WP, CG, and ZVi were statistical compared to IPSS andmore » QoL values at 6 months.ResultsA total of 93 consecutive patients were included, with mean age of 63.4 years (range, 51–86). Clinical failure, defined as IPSS > 7 or QoL > 2, was seen in four cases (4.3%). Mean reductions in prostate volumes after PAE were of 30.6% and 31.2% for WP and CG, respectively (p < 0.0001). Clinical parameters had mean decrease from 21 to 3.3 points for IPSS, and from 4.7 to 1.2 points for QoL (p < 0.0001). Baseline WP, CG, and ZVi correlated to the degree of clinical improvement (p < 0.05 for all). The baseline ZVi cut-off calculated for better clinical outcomes was > 0.45, with 85% sensitivity and 75% specificity.ConclusionsBaseline CG and WP volumes as well as ZVi presented strong correlation with clinical outcomes in patients undergoing PAE, and its assessment should be considered in pre-treatment evaluation whenever possible. Both patients and medical team should be aware of the possibility of less favorable outcomes when ZVi < 0.45.« less

Medicare Spending for Breast, Prostate, Lung, and Colorectal Cancer Patients in the Year of Diagnosis and Year of Death.

PubMed

Chen, Christopher T; Li, Ling; Brooks, Gabriel; Hassett, Michael; Schrag, Deborah

2017-07-26

To characterize spending patterns for Medicare patients with incident breast, prostate, lung, and colorectal cancer. 2007-2012 data from the Surveillance, Epidemiology, and End Results Program linked with Medicare fee-for-service claims. We calculate per-patient monthly and yearly mean and median expenditures, by cancer type, stage at diagnosis, and spending category, over the years of diagnosis and death. Over the year of diagnosis, mean spending was $35,849, $26,295, $55,597, and $63,063 for breast, prostate, lung, and colorectal cancer, respectively. Over the year of death, spending was similar across different cancer types and stage at diagnosis. Characterization of Medicare spending according to clinically meaningful categories may assist development of oncology alternative payment models and cost-effectiveness models. © Health Research and Educational Trust.

Big Data Analytics for Prostate Radiotherapy.

PubMed

Coates, James; Souhami, Luis; El Naqa, Issam

2016-01-01

Radiation therapy is a first-line treatment option for localized prostate cancer and radiation-induced normal tissue damage are often the main limiting factor for modern radiotherapy regimens. Conversely, under-dosing of target volumes in an attempt to spare adjacent healthy tissues limits the likelihood of achieving local, long-term control. Thus, the ability to generate personalized data-driven risk profiles for radiotherapy outcomes would provide valuable prognostic information to help guide both clinicians and patients alike. Big data applied to radiation oncology promises to deliver better understanding of outcomes by harvesting and integrating heterogeneous data types, including patient-specific clinical parameters, treatment-related dose-volume metrics, and biological risk factors. When taken together, such variables make up the basis for a multi-dimensional space (the "RadoncSpace") in which the presented modeling techniques search in order to identify significant predictors. Herein, we review outcome modeling and big data-mining techniques for both tumor control and radiotherapy-induced normal tissue effects. We apply many of the presented modeling approaches onto a cohort of hypofractionated prostate cancer patients taking into account different data types and a large heterogeneous mix of physical and biological parameters. Cross-validation techniques are also reviewed for the refinement of the proposed framework architecture and checking individual model performance. We conclude by considering advanced modeling techniques that borrow concepts from big data analytics, such as machine learning and artificial intelligence, before discussing the potential future impact of systems radiobiology approaches.

Big Data Analytics for Prostate Radiotherapy

PubMed Central

Coates, James; Souhami, Luis; El Naqa, Issam

2016-01-01

Radiation therapy is a first-line treatment option for localized prostate cancer and radiation-induced normal tissue damage are often the main limiting factor for modern radiotherapy regimens. Conversely, under-dosing of target volumes in an attempt to spare adjacent healthy tissues limits the likelihood of achieving local, long-term control. Thus, the ability to generate personalized data-driven risk profiles for radiotherapy outcomes would provide valuable prognostic information to help guide both clinicians and patients alike. Big data applied to radiation oncology promises to deliver better understanding of outcomes by harvesting and integrating heterogeneous data types, including patient-specific clinical parameters, treatment-related dose–volume metrics, and biological risk factors. When taken together, such variables make up the basis for a multi-dimensional space (the “RadoncSpace”) in which the presented modeling techniques search in order to identify significant predictors. Herein, we review outcome modeling and big data-mining techniques for both tumor control and radiotherapy-induced normal tissue effects. We apply many of the presented modeling approaches onto a cohort of hypofractionated prostate cancer patients taking into account different data types and a large heterogeneous mix of physical and biological parameters. Cross-validation techniques are also reviewed for the refinement of the proposed framework architecture and checking individual model performance. We conclude by considering advanced modeling techniques that borrow concepts from big data analytics, such as machine learning and artificial intelligence, before discussing the potential future impact of systems radiobiology approaches. PMID:27379211

Alterations in expressed prostate secretion-urine PSA N-glycosylation discriminate prostate cancer from benign prostate hyperplasia

PubMed Central

Sun, Chenxia; Wen, Fuping; Wang, Haifeng; Guo, Huaizu; Gao, Xu; Xu, Chuanliang; Xu, Chuanliang; Yang, Chenghua; Sun, Yinghao

2017-01-01

The prostate specific antigen (PSA) test is widely used for early diagnosis of prostate cancer (PCa). However, its limited sensitivity has led to over-diagnosis and over-treatment of PCa. Glycosylation alteration is a common phenomenon in cancer development. Different PSA glycan subforms have been proposed as diagnostic markers to better differentiate PCa from benign prostate hyperplasia (BPH). In this study, we purified PSA from expressed prostate secretions (EPS)-urine samples from 32 BPH and 30 PCa patients and provided detailed PSA glycan profiles in Chinese population. We found that most of the PSA glycans from EPS-urine were complex type biantennary glycans. We observed two major patterns in PSA glycan profiles. Overall there was no distinct separation of PSA glycan profiles between BPH and PCa patients. However, we detected a significant increase of glycan FA2 and FM5A2G2S1 in PCa when compared with BPH patients. Furthermore, we observed that the composition of FA2 glycan increased significantly in advanced PCa with Gleason score ≥8, which potentially could be translated to clinic as a marker for aggressive PCa. PMID:29100363

Alterations in expressed prostate secretion-urine PSA N-glycosylation discriminate prostate cancer from benign prostate hyperplasia.

PubMed

Jia, Gaozhen; Dong, Zhenyang; Sun, Chenxia; Wen, Fuping; Wang, Haifeng; Guo, Huaizu; Gao, Xu; Xu, Chuanliang; Xu, Chuanliang; Yang, Chenghua; Sun, Yinghao

2017-09-29

The prostate specific antigen (PSA) test is widely used for early diagnosis of prostate cancer (PCa). However, its limited sensitivity has led to over-diagnosis and over-treatment of PCa. Glycosylation alteration is a common phenomenon in cancer development. Different PSA glycan subforms have been proposed as diagnostic markers to better differentiate PCa from benign prostate hyperplasia (BPH). In this study, we purified PSA from expressed prostate secretions (EPS)-urine samples from 32 BPH and 30 PCa patients and provided detailed PSA glycan profiles in Chinese population. We found that most of the PSA glycans from EPS-urine were complex type biantennary glycans. We observed two major patterns in PSA glycan profiles. Overall there was no distinct separation of PSA glycan profiles between BPH and PCa patients. However, we detected a significant increase of glycan FA2 and FM5A2G2S1 in PCa when compared with BPH patients. Furthermore, we observed that the composition of FA2 glycan increased significantly in advanced PCa with Gleason score ≥8, which potentially could be translated to clinic as a marker for aggressive PCa.

Clinical and histopathological characteristics of patients with prostate cancer in the BioBank Japan project.

PubMed

Ukawa, Shigekazu; Nakamura, Koshi; Okada, Emiko; Hirata, Makoto; Nagai, Akiko; Yamagata, Zentaro; Muto, Kaori; Matsuda, Koichi; Ninomiya, Toshiharu; Kiyohara, Yutaka; Kamatani, Yoichiro; Kubo, Michiaki; Nakamura, Yusuke; Tamakoshi, Akiko

2017-03-01

Prostate cancer is the sixth leading cause of cancer-related deaths in Japan. We aimed to elucidate the clinical and histopathological characteristics of patients with prostate cancer in the BioBank Japan (BBJ) project. Four thousand, seven hundred and ninety-three patients diagnosed with prostate cancer in the BBJ project were included. Clinical and histopathological data, including causes of death, were analyzed. Relative survival (RS) rates of prostate cancer were calculated. Four thousand, one hundred and seventy-one prostate cancer patients with available histological data had adenocarcinoma. The mean age of the patients was 72.5 years. The proportion of patients who were non-smokers, non-drinkers, had a normal body mass index, did not exercise, had a normal prostate-specific antigen level, and had a family history of prostate cancer were 30.7%, 28.0%, 66.6%, 58.1%, 67.6%, and 6.5%, respectively. The proportion of patients with Stage II, III, and IV disease were 24.4%, 7.3%, and 4.4%, respectively. After limiting to patients with a time from the initial diagnosis of prostate cancer to entry into the study cohort of ≤90 days (n = 869), the 5- and 10-year RS rates were 96.3% and 100.5%, respectively, although we were unable to consider management strategies due to a plenty of data missing. We provide an overview of patients with prostate cancer in the BBJ project. Our findings, coupled with those from various high throughput "omics" technologies, will contribute to the implementation of prevention interventions and medical management of prostate cancer patients. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

A Pooled Analysis of 15 Prospective Cohort Studies on the Association between Fruit, Vegetable, and Mature Bean Consumption and Risk of Prostate Cancer.

PubMed

Petimar, Joshua; Wilson, Kathryn M; Wu, Kana; Wang, Molin; Albanes, Demetrius; van den Brandt, Piet A; Cook, Michael B; Giles, Graham G; Giovannucci, Edward L; Goodman, Gary E; Goodman, Phyllis J; Håkansson, Niclas; Helzlsouer, Kathy; Key, Timothy J; Kolonel, Laurence N; Liao, Linda M; Männistö, Satu; McCullough, Marjorie L; Milne, Roger L; Neuhouser, Marian L; Park, Yikyung; Platz, Elizabeth A; Riboli, Elio; Sawada, Norie; Schenk, Jeannette M; Tsugane, Shoichiro; Verhage, Bas; Wang, Ying; Wilkens, Lynne R; Wolk, Alicja; Ziegler, Regina G; Smith-Warner, Stephanie A

2017-08-01

Background: Relationships between fruit, vegetable, and mature bean consumption and prostate cancer risk are unclear. Methods: We examined associations between fruit and vegetable groups, specific fruits and vegetables, and mature bean consumption and prostate cancer risk overall, by stage and grade, and for prostate cancer mortality in a pooled analysis of 15 prospective cohorts, including 52,680 total cases and 3,205 prostate cancer-related deaths among 842,149 men. Diet was measured by a food frequency questionnaire or similar instrument at baseline. We calculated study-specific relative risks using Cox proportional hazards regression, and then pooled these estimates using a random effects model. Results: We did not observe any statistically significant associations for advanced prostate cancer or prostate cancer mortality with any food group (including total fruits and vegetables, total fruits, total vegetables, fruit and vegetable juice, cruciferous vegetables, and tomato products), nor specific fruit and vegetables. In addition, we observed few statistically significant results for other prostate cancer outcomes. Pooled multivariable relative risks comparing the highest versus lowest quantiles across all fruit and vegetable exposures and prostate cancer outcomes ranged from 0.89 to 1.09. There was no evidence of effect modification for any association by age or body mass index. Conclusions: Results from this large, international, pooled analysis do not support a strong role of collective groupings of fruits, vegetables, or mature beans in prostate cancer. Impact: Further investigation of other dietary exposures, especially indicators of bioavailable nutrient intake or specific phytochemicals, should be considered for prostate cancer risk. Cancer Epidemiol Biomarkers Prev; 26(8); 1276-87. ©2017 AACR . ©2017 American Association for Cancer Research.

Investigation of the Anti-Prostate Cancer Properties of Marine-Derived Compounds

PubMed Central

Fan, Meiqi; Nath, Amit Kumar; Tang, Yujiao; Choi, Young-Jin; Debnath, Trishna; Choi, Eun-Ju

2018-01-01

This review focuses on marine compounds with anti-prostate cancer properties. Marine species are unique and have great potential for the discovery of anticancer drugs. Marine sources are taxonomically diverse and include bacteria, cyanobacteria, fungi, algae, and mangroves. Marine-derived compounds, including nucleotides, amides, quinones, polyethers, and peptides are biologically active compounds isolated from marine organisms such as sponges, ascidians, gorgonians, soft corals, and bryozoans, including those mentioned above. Several compound classes such as macrolides and alkaloids include drugs with anti-cancer mechanisms, such as antioxidants, anti-angiogenics, antiproliferatives, and apoptosis-inducing drugs. Despite the diversity of marine species, most marine-derived bioactive compounds have not yet been evaluated. Our objective is to explore marine compounds to identify new treatment strategies for prostate cancer. This review discusses chemically and pharmacologically diverse marine natural compounds and their sources in the context of prostate cancer drug treatment. PMID:29757237

Chronic Pelvic Pain Development and Prostate Inflammation in Strains of Mice With Different Susceptibility to Experimental Autoimmune Prostatitis.

PubMed

Breser, Maria L; Motrich, Ruben D; Sanchez, Leonardo R; Rivero, Virginia E

2017-01-01

Experimental autoimmune prostatitis (EAP) is an autoimmune inflammatory disease of the prostate characterized by peripheral prostate-specific autoimmune responses associated with prostate inflammation. EAP is induced in rodents upon immunization with prostate antigens (PAg) plus adjuvants and shares important clinical and immunological features with the human disease chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). EAP was induced in young NOD, C57BL/6, and BALB/c male mice by immunization with PAg plus complete Freund́s adjuvant. Tactile allodynia was assessed using Von Frey fibers as a measure of pelvic pain at baseline and at different time points after immunization. Using conventional histology, immunohistochemistry, FACS analysis, and protein arrays, an interstrain comparative study of prostate cell infiltration and inflammation was performed. Chronic pelvic pain development was similar between immunized NOD and C57BL/6 mice, although the severity of leukocyte infiltration was greater in the first case. Coversely, minimal prostate cell infiltration was observed in immunized BALB/c mice, who showed no pelvic pain development. Increased numbers of mast cells, mostly degranulated, were detected in prostate samples from NOD and C57BL/6 mice, while lower total counts and resting were observed in BALB/c mice. Prostate tissue from NOD mice revealed markedly increased expression levels of inflammatory cytokines, chemokines, adhesion molecules, vascular endothelial growth factor, and metalloproteinases. Similar results, but to a lesser extent, were observed when analyzing prostate tissue from C57BL/6 mice. On the contrary, the expression of the above mediators was very low in prostate tissue from immunized BALB/c mice, showing significantly slight increments only for CXCL1 and IL4. Our results provide new evidence indicating that NOD, C57BL/6, and BALB/c mice develop different degrees of chronic pelvic pain, type, and amount of prostate cell infiltration and secretion of inflammatory mediators. Our results corroborate and support the notion that mice with different genetic background have different susceptibility to EAP induction. Prostate 77:94-104, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Prospective study of DNA methylation at chromosome 8q24 in peripheral blood and prostate cancer risk.

PubMed

Barry, Kathryn Hughes; Moore, Lee E; Sampson, Joshua N; Koutros, Stella; Yan, Liying; Meyer, Ann; Reddy, Mahitha; Oler, Andrew J; Cook, Michael B; Fraumeni, Joseph F; Yeager, Meredith; Amundadottir, Laufey T; Berndt, Sonja I

2017-05-23

Chromosome 8q24 has emerged as an important genetic susceptibility region for several cancers, including prostate cancer; however, little is known about the contribution of DNA methylation in this region to risk. We prospectively evaluated DNA methylation at 8q24 in relation to prostate cancer using pre-diagnostic blood samples from 694 prostate cancer cases (including 172 aggressive cases) and 703 controls in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. We used logistic regression to estimate odds ratios and 95% confidence intervals. Although none remained significant after adjustment for multiple testing (q>0.05), of the 50 CpG sites meeting quality control, we identified 8 sites that were nominally associated with prostate cancer (P trend <0.05), including 6 correlated (Spearman ρ: 0.20-0.52) sites in POU5F1B and 2 intergenic sites (most significant site: Chr8:128428897 in POU5F1B, P trend =0.01). We also identified two correlated (ρ=0.39) sites in MYC (Chr8:128753187 and Chr8:128753154) that were associated with aggressive (P trend =0.02 and 0.03), but not non-aggressive disease (P trend =0.70 and 0.20; P heterogeneity =0.01 and 4.6 × 10 -3 ). These findings persisted after adjustment for the top 8q24 prostate cancer variants in our study. Although requiring replication, our findings provide some evidence that 8q24 DNA methylation levels may be associated with prostate cancer risk.

Aromatase up-regulation, insulin and raised intracellular oestrogens in men, induce adiposity, metabolic syndrome and prostate disease, via aberrant ER-α and GPER signalling.

PubMed

Williams, Graeme

2012-04-04

For some years now, reduced testosterone levels have been related to obesity, insulin resistance, type 2 diabetes, heart disease, benign prostatic hypertrophy and even prostate cancer--often considered guilty more by association, than actual cause--with little attention paid to the important role of increased intracellular oestrogen, in the pathogenesis of these chronic diseases. In the final stage of the steroidogenic cascade, testosterone is metabolised to oestradiol by P450 aromatase, in the cytoplasm of adipocytes, breast cells, endothelial cells and prostate cells, to increase intracellular oestradiol concentration at the expense of testosterone. It follows therefore, that any compound that up-regulates aromatase, or any molecule that mimics oestrogen, will not only increase the activation of the mainly proliferative, classic ER-α, oestrogen receptors to induce adipogenesis and growth disorders in oestrogen-sensitive tissues, but also activate the recently identified transmembrane G protein-coupled oestrogen receptors (GPER), and deleteriously alter important intracellular signalling sequences, that promote mitogenic growth and endothelial damage. This paper simplifies how stress, xeno-oestrogens, poor dietary choices and reactive toxins up-regulate aromatase to increase intracellular oestradiol production; how oestradiol in combination with leptin and insulin cause insulin resistance and leptin resistance through aberrant serine phosphorylation; how the increased oestradiol, insulin and leptin stimulate rapid, non-genomic G protein-coupled phosphorylation cascades, to increase fat deposition and create the vasoconstrictive, dyslipidemic features of metabolic syndrome; how aberrant GPER signalling induces benign prostatic hypertrophy; and how increased intracellular oestradiol stimulates mitogenic change and tumour-cell activators, to cause prostate cancer. In essence, the up-regulation of aromatase produces increased intracellular oestradiol, increases ER-α activation and increases GPER activation, in combination with insulin, to cause aberrant downstream transduction signaling, and thus induce metabolic syndrome and mitogenic prostate growth. To understand this fact, that raised intracellular oestradiol levels in men, induce and promote obesity, gynecomastia, metabolic syndrome, type two diabetes, benign prostatic hypertrophy and prostate cancer, rather than low testosterone, represents a shift in medical thinking, a new awareness, that will reduce the rising incidence of obesity, metabolic syndrome and prostate disease, and significantly improve the health of men worldwide. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Cost analysis of skeletal-related events in Spanish patients with bone metastases from solid tumours.

PubMed

Durán, I; Garzón, C; Sánchez, A; García-Carbonero, I; Pérez-Gracia, J L; Seguí-Palmer, M Á; Wei, R; Restovic, G; Gasquet, J A; Gutiérrez, L

2014-03-01

To estimate the cost per skeletal-related event (SRE) in patients with bone metastases secondary to solid tumours in the Spanish healthcare setting. Patients diagnosed with bone metastases secondary to breast, prostate or lung cancer were included in this multicentre, observational study. SREs are defined as pathologic fracture (vertebral and non-vertebral fracture), radiation to bone, spinal cord compression or surgery to bone. Health resource utilisation associated with these events (inpatient stays, outpatient, emergency room and home health visits, nursing home stays and procedures) were collected retrospectively for all SREs that occurred in the 97 days prior to enrolment and prospectively during follow-up. Unit costs were obtained from the 2010 eSalud healthcare costs database. A total of 93 Spanish patients with solid tumours were included (31 had breast cancer, 21 prostate cancer and 41 lung cancer), contributing a total of 143 SREs to this cost analysis. Inpatient stays (between 9.0 and 29.9 days of mean length of stay per inpatient stay by SRE type) and outpatient visits (between 1.7 and 6.4 mean visits per SRE type) were the most frequently reported types of health resources utilised. The mean cost per SRE was between 2,377.79 (radiation to bone) and 7,902.62 (spinal cord compression). SREs are associated with a significant consumption of healthcare resources that generate a substantial economic burden for the Spanish healthcare system.

Factors Associated With the Prevalence of Prostate Cancer in Rural Saskatchewan: The Saskatchewan Rural Health Study.

PubMed

Sharma, Meenu; Lawson, Joshua A; Kanthan, Rani; Karunanayake, Chandima; Hagel, Louise; Rennie, Donna; Dosman, James A; Pahwa, Punam

2016-01-01

Prostate cancer is the most commonly diagnosed cancer in Canadian males, and it is the third most common cause of cancer-related deaths in men. Some studies suggest that occupational exposure may be associated with prostate cancer. However, the etiology of prostate cancer is ambiguous. The purpose of this study was to assess the rural occupational exposure, including farming, as a determinant of prostate cancer in rural men. We investigated the prevalence of prostate cancer and its putative relationship between rural exposures in the Saskatchewan province of Canada. In 2010, a baseline mailed survey was conducted of 11,982 households located in 4 geographic regions (southwest, southeast, northwest, and northeast) of rural Saskatchewan, Canada. The questionnaires collected information on individual and contextual determinants from a rural population of men. In total 2,938 males older than 45 years were included in the logistic regression analysis. The age-standardized prevalence of prostate cancer was 3.32%. Farm residence was a significant risk factor associated with prevalence of prostate cancer while farming occupation and duration were not. Men who were exposed to insecticides and fungicides together (OR [95% CI] = 2.23 [1.15-4.33], P = .02) at work showed an increased potential risk compared to the nonexposed. The effect of farm/nonfarm residence on prevalence of prostate cancer differed depending on personal smoking history and family history of cancer. Workplace exposure to insecticides and fungicides together were statistically significantly associated with prevalence of prostate cancer. © 2015 National Rural Health Association.

Evaluation of [-2] proPSA and Prostate Health Index (phi) for the detection of prostate cancer: a systematic review and meta-analysis.

PubMed

Filella, Xavier; Giménez, Nuria

2013-04-01

The usefulness of %[-2] proPSA and Prostate Health Index (phi) in the detection of prostate cancer are currently unknown. It has been suggested that these tests can distinguish prostate cancer from benign prostatic diseases better than PSA or %fPSA. We performed a systematic review and meta-analysis of the available scientific evidence to evaluate the clinical usefulness of %[-2] proPSA and phi. Relevant published papers were identified by searching computerized bibliographic systems. Data on sensitivity and specificity were extracted from 12 studies: 10 studies about %[-2] proPSA (3928 patients in total, including 1762 with confirmed prostate cancer) and eight studies about phi (2919 patients in total, including 1515 with confirmed prostate cancer). The sensitivity for the detection of prostate cancer was 90% for %[-2] proPSA and phi, while the pooled specificity was 32.5% (95% CI 30.6-34.5) and 31.6% (95% CI 29.2-34.0) for %[-2] proPSA and phi, respectively. The measurement of %[-2] proPSA improves the accuracy of prostate cancer detection in comparison with PSA or %fPSA, particularly in the group of patients with PSA between 2 μg/L and 10 μg/L. Similar results were obtained measuring phi. Using these tests, it is possible to reduce the number of unnecessary biopsies, maintaining a high cancer detection rate. Published results also showed that %[-2] proPSA and phi are related to the aggressiveness of the tumor.

Metastatic prostate adenocarcinoma to the penis: a series of 29 cases with predilection for ductal adenocarcinoma.

PubMed

Ellis, Carla L; Epstein, Jonathan I

2015-01-01

Twenty-nine men with metastatic prostate adenocarcinoma to the penis were identified at our institution between 1993 and 2013. Of the 29 patients, 19 had a prior history of adenocarcinoma of the prostate, and 8 of those had ductal features in the primary lesion. Sixteen of 29 revealed ductal features in the metastasis. Seven of the 8 cases with ductal features in the primary had ductal features in the penile metastasis. Seven penile metastases were proven to be of prostatic origin solely by immunohistochemistry. Three cases were originally misdiagnosed as urothelial carcinoma upon review of the penile lesion. Other variant morphologies in the metastases included sarcomatoid carcinoma, small cell carcinoma, and adenosquamous carcinoma. In summary, prostate carcinoma involving the penis displays ductal features considerably more often than prostate cancer in general. Features that can cause difficulty in recognizing metastatic prostate adenocarcinoma to the penis include the unusual anatomic site for prostate cancer, poor differentiation, an increased prevalence of variant morphology, a long interval from the primary lesion, and, in some cases, no documented history of a primary prostatic lesion. Immunohistochemical analysis should be performed to rule out prostate carcinoma in penile/penile urethral tumors with morphology that differs from typical squamous or urothelial carcinoma. Even in the setting of metastatic disease, there is a critical need for an accurate diagnosis so that the appropriate therapy can be initiated, symptomatic relief can be provided, and long-term survival achieved in some cases, while at the same time avoiding penectomy for a misdiagnosis of a primary penile cancer.

Potency of a novel saw palmetto ethanol extract, SPET-085, for inhibition of 5alpha-reductase II.

PubMed

Pais, Pilar

2010-08-01

The nicotinamide adenine dinucleotide phosphate (NADPH)-dependent membrane protein 5alpha-reductase irreversibly catalyses the conversion of testosterone to the most potent androgen, 5alpha-dihydrotestosterone (DHT). In humans, two 5alpha-reductase isoenyzmes are expressed: type I and type II. Type II is found primarily in prostate tissue. Saw palmetto extract (SPE) has been widely used for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH). The mechanisms of the pharmacological effects of SPE include the inhibition of 5alpha-reductase, among other actions. Clinical studies of SPE have been equivocal, with some showing significant results and others not. These inconsistent results may be due, in part, to varying bioactivities of the SPE used in the studies. The aim of the present study was to determine the in vitro potency of a novel saw palmetto ethanol extract (SPET-085), an inhibitor of the 5alpha-reductase isoenzyme type II, in a cell-free test system. On the basis of the enzymatic conversion of the substrate androstenedione to the 5alpha-reduced product 5alpha-androstanedione, the inhibitory potency was measured and compared to those of finasteride, an approved 5alpha-reductase inhibitor. SPET-085 concentration-dependently inhibited 5alpha-reductase type II in vitro (IC(50)=2.88+/-0.45 microg/mL). The approved 5alpha-reductase inhibitor, finasteride, tested as positive control, led to 61% inhibition of 5alpha-reductase type II. SPET-085 effectively inhibits the enzyme that has been linked to BPH, and the amount of extract required for activity is very low compared to data reported for other extracts. It can be concluded from data in the literature that SPET-085 is as effective as a hexane extract of saw palmetto that exhibited the highest levels of bioactivity, and is more effective than other SPEs tested. This study confirmed that SPET-085 has prostate health-promoting bioactivity that also corresponds favorably to that reported for the established prescription drug standard of therapy, finasteride.

[Age peculiarities in prostate cancer detection based on the prostate-specific antigen and its alterations control].

PubMed

Ponkratov, S V; Kheyfets, V Kh; Kagan, O F

2017-01-01

Data on epidemiology of a prostate cancer are presented in article, high prevalence and body height of a case rate cause relevance of researches on this oncopathology. It is shown that the number augmentation for the first time of the taped cases is bound including to the program of a screening of inspection of men by determination of level of prostates-specific antigen (PSA). Modern diagnostic methods of identification of modifications of PSA, possessing larger sensitivity and specificity concerning a prostate cancer are lit. The attention to change of level of PSA depending on age is focused that needs to be considered at diagnostics of malignant neoplasms of a prostate.

Prostate Cancer: Serum and Tissue Markers

PubMed Central

Miller, Gary J; Brawer, Michael K; Sakr, Wael A; Thrasher, J Brantley; Townsend, Ronald

2001-01-01

The detection of prostate cancer, its clinical staging, and the prediction of its prognosis remain topics of paramount importance in clinical management. The digital rectal exam, although once the “gold standard,” has been largely supplanted by a variety of techniques including serum and tissue-based assays. This article reviews recent progress in the development of prostate-specific antigen assays with greater specificity; molecular markers for prostate cancer (DNA ploidy, nuclear morphometry, markers of proliferation, and cell adhesion molecules); the link between vitamin D deficiency and the clinical emergence of prostate cancer; the possible correlation of serum insulin-like growth factor levels with the risk for developing prostate cancer; and the latest advances in radiologic staging. PMID:16985995

[Magnetic resonance semiotics of prostate cancer according to the PI-RADS classification. The clinical diagnostic algorithm of a study].

PubMed

Korobkin, A S; Shariya, M A; Chaban, A S; Voskanvan, G A; Vinarov, A Z

2015-01-01

to elaborate the magnetic resonance imaging (MRI) signs of prostate cancer (PC) in accordance with the PI-RADS classification during multiparametric MRI (mpMRI). A total of 89 men aged 20 to 82 years were examined. A control group consisted of 8 (9%) healthy volunteers younger than 30 years of age with no urological history to obtain control images and MRI plots and 20 (22.5%) men aged 26-76 years, whose morphological changes were inflammatory and hyperplastic. The second age-matched group included 61 (68.5%) patients diagnosed with prostate cancer at morphological examination. A set of studies included digital rectal examination, serum prostate-specific antigen, and transrectal ultrasound-guided prostate biopsy. All the patients underwent prostate mpMRI applying a 3.0 T Achieva MRI scanner (Philips, the Netherlands). The patients have been found to have mpMRI signs that were typical of PC; its MRI semiotics according to the PI-RADS classification is presented. Each mpMRI procedure has been determined to be of importance and informative value in detecting PC. The comprehensive mpMRI approach to diagnosing PC improves the quality and diagnostic value of prostate MRI.

A review of clinical effects associated with metabolic syndrome and exercise in prostate cancer patients.

PubMed

Kiwata, J L; Dorff, T B; Schroeder, E T; Gross, M E; Dieli-Conwright, C M

2016-12-01

Androgen deprivation therapy (ADT), a primary treatment for locally advanced or metastatic prostate cancer, is associated with the adverse effects on numerous physiologic parameters, including alterations in cardiometabolic variables that overlap with components of the metabolic syndrome (MetS). As MetS is an established risk factor for cardiovascular mortality and treatment for prostate cancer has been associated with the development of MetS, interventions targeting cardiometabolic factors have been investigated in prostate cancer patients to attenuate the detrimental effects of ADT. Much support exists for exercise interventions in improving MetS variables in insulin-resistant adults, but less evidence is available in men with prostate cancer. Regular exercise, when performed at appropriate intensities and volumes, can elicit improvements in ADT-related adverse effects, including MetS, and contributes to the growing body of literature supporting the role of exercise in cancer survivorship. This review (1) discusses the biologic inter-relationship between prostate cancer, ADT and MetS, (2) evaluates the current literature in support of exercise in targeting MetS and (3) describes the physiological mechanisms by which exercise may favorably alter MetS risk factors in prostate cancer patients on ADT.

A review of clinical effects associated with metabolic syndrome and exercise in prostate cancer patients

PubMed Central

Kiwata, J L; Dorff, T B; Schroeder, E T; Gross, M E; Dieli-Conwright, C M

2016-01-01

Androgen deprivation therapy (ADT), a primary treatment for locally advanced or metastatic prostate cancer, is associated with the adverse effects on numerous physiologic parameters, including alterations in cardiometabolic variables that overlap with components of the metabolic syndrome (MetS). As MetS is an established risk factor for cardiovascular mortality and treatment for prostate cancer has been associated with the development of MetS, interventions targeting cardiometabolic factors have been investigated in prostate cancer patients to attenuate the detrimental effects of ADT. Much support exists for exercise interventions in improving MetS variables in insulin-resistant adults, but less evidence is available in men with prostate cancer. Regular exercise, when performed at appropriate intensities and volumes, can elicit improvements in ADT-related adverse effects, including MetS, and contributes to the growing body of literature supporting the role of exercise in cancer survivorship. This review (1) discusses the biologic inter-relationship between prostate cancer, ADT and MetS, (2) evaluates the current literature in support of exercise in targeting MetS and (3) describes the physiological mechanisms by which exercise may favorably alter MetS risk factors in prostate cancer patients on ADT. PMID:27349496

Evaluation of prostate cancer antigen 3 for detecting prostate cancer: a systematic review and meta-analysis

NASA Astrophysics Data System (ADS)

Cui, Yong; Cao, Wenzhou; Li, Quan; Shen, Hua; Liu, Chao; Deng, Junpeng; Xu, Jiangfeng; Shao, Qiang

2016-05-01

Previous studies indicate that prostate cancer antigen 3 (PCA3) is highly expressed in prostatic tumors. However, its clinical value has not been characterized. The aim of this study was to investigate the clinical value of the urine PCA3 test in the diagnosis of prostate cancer by pooling the published data. Clinical trials utilizing the urine PCA3 test for diagnosing prostate cancer were retrieved from PubMed and Embase. A total of 46 clinical trials including 12,295 subjects were included in this meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio (+LR), negative likelihood ratio (-LR), diagnostic odds ratio (DOR) and area under the curve (AUC) were 0.65 (95% confidence interval [CI]: 0.63-0.66), 0.73 (95% CI: 0.72-0.74), 2.23 (95% CI: 1.91-2.62), 0.48 (95% CI: 0.44-0.52), 5.31 (95% CI: 4.19-6.73) and 0.75 (95% CI: 0.74-0.77), respectively. In conclusion, the urine PCA3 test has acceptable sensitivity and specificity for the diagnosis of prostate cancer and can be used as a non-invasive method for that purpose.

[Causes of death among prostate cancer patients of different ages].

PubMed

Dariy, E V

2016-02-01

To date, there is no unified approach to evaluating and treating patients with suspected prostate cancer taking into account their age and comorbidities. That was the rationale for conducting this study. To assess the clinical course of prostate cancer in men of all ages with comorbidities. The study included 408 patients aged 50 to 92 years (mean age 74.3 years) with histologically verified prostate cancer. 30 (7.4%) patients had stage T1 disease, 273 (66.9%) - T2, 91 (22.3%) - T3 and 14 (3.4%) - T4. The maximum follow-up was 22 years, the minimum one - 6 months (on average 15.4 years). During the follow-up 159 patients died (39%), 51 of them (32%) of prostate cancer, 108 (68%) - from other diseases. Among the latter the causes of death were cancer (20.4%), cardiovascular and bronchopulmonary diseases (79.6%). Cancer-specific survival rate was 41.4 +/-12,4%, the survival rate for other diseases 23.4 +/-10,6% (p<0.05). We need a differentiated approach to selecting treatment for patients with prostate cancer, especially of old age, including the option for active surveillance of patients with clinically insignificant prostate cancer.

Prostate cancer prediction using the random forest algorithm that takes into account transrectal ultrasound findings, age, and serum levels of prostate-specific antigen.

PubMed

Xiao, Li-Hong; Chen, Pei-Ran; Gou, Zhong-Ping; Li, Yong-Zhong; Li, Mei; Xiang, Liang-Cheng; Feng, Ping

2017-01-01

The aim of this study is to evaluate the ability of the random forest algorithm that combines data on transrectal ultrasound findings, age, and serum levels of prostate-specific antigen to predict prostate carcinoma. Clinico-demographic data were analyzed for 941 patients with prostate diseases treated at our hospital, including age, serum prostate-specific antigen levels, transrectal ultrasound findings, and pathology diagnosis based on ultrasound-guided needle biopsy of the prostate. These data were compared between patients with and without prostate cancer using the Chi-square test, and then entered into the random forest model to predict diagnosis. Patients with and without prostate cancer differed significantly in age and serum prostate-specific antigen levels (P < 0.001), as well as in all transrectal ultrasound characteristics (P < 0.05) except uneven echo (P = 0.609). The random forest model based on age, prostate-specific antigen and ultrasound predicted prostate cancer with an accuracy of 83.10%, sensitivity of 65.64%, and specificity of 93.83%. Positive predictive value was 86.72%, and negative predictive value was 81.64%. By integrating age, prostate-specific antigen levels and transrectal ultrasound findings, the random forest algorithm shows better diagnostic performance for prostate cancer than either diagnostic indicator on its own. This algorithm may help improve diagnosis of the disease by identifying patients at high risk for biopsy.

Telomere structure and maintenance gene variants and risk of five cancer types.

PubMed

Karami, Sara; Han, Younghun; Pande, Mala; Cheng, Iona; Rudd, James; Pierce, Brandon L; Nutter, Ellen L; Schumacher, Fredrick R; Kote-Jarai, Zsofia; Lindstrom, Sara; Witte, John S; Fang, Shenying; Han, Jiali; Kraft, Peter; Hunter, David J; Song, Fengju; Hung, Rayjean J; McKay, James; Gruber, Stephen B; Chanock, Stephen J; Risch, Angela; Shen, Hongbing; Haiman, Christopher A; Boardman, Lisa; Ulrich, Cornelia M; Casey, Graham; Peters, Ulrike; Amin Al Olama, Ali; Berchuck, Andrew; Berndt, Sonja I; Bezieau, Stephane; Brennan, Paul; Brenner, Hermann; Brinton, Louise; Caporaso, Neil; Chan, Andrew T; Chang-Claude, Jenny; Christiani, David C; Cunningham, Julie M; Easton, Douglas; Eeles, Rosalind A; Eisen, Timothy; Gala, Manish; Gallinger, Steven J; Gayther, Simon A; Goode, Ellen L; Grönberg, Henrik; Henderson, Brian E; Houlston, Richard; Joshi, Amit D; Küry, Sébastien; Landi, Mari T; Le Marchand, Loic; Muir, Kenneth; Newcomb, Polly A; Permuth-Wey, Jenny; Pharoah, Paul; Phelan, Catherine; Potter, John D; Ramus, Susan J; Risch, Harvey; Schildkraut, Joellen; Slattery, Martha L; Song, Honglin; Wentzensen, Nicolas; White, Emily; Wiklund, Fredrik; Zanke, Brent W; Sellers, Thomas A; Zheng, Wei; Chatterjee, Nilanjan; Amos, Christopher I; Doherty, Jennifer A

2016-12-15

Telomeres cap chromosome ends, protecting them from degradation, double-strand breaks, and end-to-end fusions. Telomeres are maintained by telomerase, a reverse transcriptase encoded by TERT, and an RNA template encoded by TERC. Loci in the TERT and adjoining CLPTM1L region are associated with risk of multiple cancers. We therefore investigated associations between variants in 22 telomere structure and maintenance gene regions and colorectal, breast, prostate, ovarian, and lung cancer risk. We performed subset-based meta-analyses of 204,993 directly-measured and imputed SNPs among 61,851 cancer cases and 74,457 controls of European descent. Independent associations for SNP minor alleles were identified using sequential conditional analysis (with gene-level p value cutoffs ≤3.08 × 10 -5 ). Of the thirteen independent SNPs observed to be associated with cancer risk, novel findings were observed for seven loci. Across the DCLRE1B region, rs974494 and rs12144215 were inversely associated with prostate and lung cancers, and colorectal, breast, and prostate cancers, respectively. Across the TERC region, rs75316749 was positively associated with colorectal, breast, ovarian, and lung cancers. Across the DCLRE1B region, rs974404 and rs12144215 were inversely associated with prostate and lung cancers, and colorectal, breast, and prostate cancers, respectively. Near POT1, rs116895242 was inversely associated with colorectal, ovarian, and lung cancers, and RTEL1 rs34978822 was inversely associated with prostate and lung cancers. The complex association patterns in telomere-related genes across cancer types may provide insight into mechanisms through which telomere dysfunction in different tissues influences cancer risk. © 2016 UICC.

Irreversible Electroporation for Prostate Cancer as Salvage Treatment Following Prior Radiation and Cryotherapy.

PubMed

Murray, Katie S; Akin, Oguz; Coleman, Jonathan A

2017-01-01

Salvage treatment options after localized primary treatment failure of prostate cancer are limited and associated with risk for serious complications. We report on the management details of a 57-year-old African American man treated with partial-gland ablation using irreversible electroporation following local recurrence after brachytherapy and prior salvage cryoablation. Therapeutic and functional outcomes were assessed by conventional means, including serum prostate-specific antigen values and prostate biopsy results.

Development of a Novel, Non-Invasive Diagnostic Test for Prostate Cancer

DTIC Science & Technology

2006-01-01

Chang JJ, Bhargava V , Shinohara K. The optimal systematic prostate biopsy scheme should include 8 rather than 6 biopsies: results of a prospective...sextant and laterally directed biopsies for the detection of prostate cancer. J Urol, 2001, 165:1554-9. 19. Djavan B, Ravery V , Zlotta A, Dobronski P...Smith-Jones PM, Navarro V , Goldsmith SJ, Bander NH. Radioimmunotherapy of prostate cancer in human xenografts using monoclonal antibodies specific to

Proteolytic Processing of Laminin-332 by Hepsin and Matriptase and Its Role in Prostate Cancer Progression

DTIC Science & Technology

2011-09-01

epithelial tumors, including breast, cervix , esophagus, liver, mesothelium, prostate, and colorectal cancers [36,38,61–69]. Interestingly, in the case of...Proteolytic Processing of Laminin-332 by Hepsin and Matriptase and Its Role in Prostate Cancer Progression Manisha Tripathi The Vanderbilt University...Nashville, TN 37203 Laminin-332 is lost in prostate cancer progression. Laminin-332 is known to be cleaved by various cell surface proteases

Are prostatic calculi independent predictive factors of lower urinary tract symptoms?

PubMed

Park, Sung-Woo; Nam, Jong-Kil; Lee, Sang-Don; Chung, Moon-Kee

2010-03-01

We determined the correlation between prostatic calculi and lower urinary tract symptoms (LUTS), as well as the predisposing factors of prostatic calculi. Of the 1 527 patients who presented at our clinic for LUTS, 802 underwent complete evaluations, including transrectal ultrasonography, voided bladder-3 specimen and international prostatic symptoms score (IPSS). A total of 335 patients with prostatic calculi and 467 patients without prostatic calculi were divided into calculi and no calculi groups, respectively. Predictive factors of severe LUTS and prostatic calculi were determined using uni/multivariate analysis. The overall IPSS score was 15.7 +/- 9.2 and 14.1 +/- 9.2 in the calculi and no calculi group, respectively (P = 0.013). The maximum flow rate was 12.1 +/- 6.9 and 14.2 +/- 8.2 mL s(-1) in the calculi and no calculi group, respectively (P = 0.003). On univariate analysis for predicting factors of severe LUTS, differences on age (P = 0.042), prostatic calculi (P = 0.048) and prostatitis (P = 0.018) were statistically significant. However, on multivariate analysis, no factor was significant. On multivariate analysis for predisposing factors of prostatic calculi, differences on age (P < 0.001) and prostate volume (P = 0.001) were significant. To our knowledge, patients who have prostatic calculi complain of more severe LUTS. However, prostatic calculi are not an independent predictive factor of severe LUTS. Therefore, men with prostatic calculi have more severe LUTS not only because of prostatic calculi but also because of age and other factors. In addition, old age and large prostate volume are independent predisposing factors for prostatic calculi.

Immunohistochemical expression of interleukin-2 receptor and interleukin-6 in patients with prostate cancer and benign prostatic hyperplasia: association with asymptomatic inflammatory prostatitis NIH category IV.

PubMed

Engelhardt, Paul Friedrich; Seklehner, Stephan; Brustmann, Hermann; Lusuardi, Lukas; Riedl, Claus R

2015-04-01

This study prospectively investigated the immunohistochemical expression of interleukin-2 receptor (IL-2R) and interleukin-6 (IL-6) in patients with prostate cancer and benign prostatic hyperplasia (BPH), and a possible association of these conditions with asymptomatic inflammatory prostatitis National Institutes of Health (NIH) category IV. The study included 139 consecutive patients who underwent transurethral resection of the prostate and transvesical enucleation of the prostate (n = 82) or radical prostatectomy (n = 57). To characterize inflammatory changes the criteria proposed by Irani et al. [J Urol 1997;157:1301-3] were used. IL-2R and IL-6 expression was studied by a standard immunohistochemical method. Results were correlated with tumour, node, metastasis stage, Gleason scores, total prostate-specific antigen, International Prostate Symptom Score and body mass index. IL-2R and IL-6 expression was significantly higher in neoplastic prostate cancer tissue than in normal tissue of prostate cancer patients (p < 0.001 and p < 0.04, respectively). Prostate cancer patients with prostatitis showed significantly higher IL-2R expression than those without inflammation (p < 0.03). In patients with BPH, expression of IL-2R as well as IL-6 was higher in patients with prostatitis than in those without (p < 0.01 and p < 0.02, respectively). IL-2R and IL-6 expression was significantly higher in prostate cancer tissue than in normal tissue. Patients with asymptomatic inflammatory prostatitis NIH category IV showed significantly greater activity.

IL17 Mediates Pelvic Pain in Experimental Autoimmune Prostatitis (EAP)

PubMed Central

Murphy, Stephen F.; Schaeffer, Anthony J.; Done, Joseph; Wong, Larry; Bell-Cohn, Ashlee; Roman, Kenny; Cashy, John; Ohlhausen, Michelle; Thumbikat, Praveen

2015-01-01

Chronic pelvic pain syndrome (CPPS) is the most common form of prostatitis, accounting for 90–95% of all diagnoses. It is a complex multi-symptom syndrome with unknown etiology and limited effective treatments. Previous investigations highlight roles for inflammatory mediators in disease progression by correlating levels of cytokines and chemokines with patient reported symptom scores. It is hypothesized that alteration of adaptive immune mechanisms results in autoimmunity and subsequent development of pain. Mouse models of CPPS have been developed to delineate these immune mechanisms driving pain in humans. Using the experimental autoimmune prostatitis (EAP) in C57BL/6 mice model of CPPS we examined the role of CD4+T-cell subsets in the development and maintenance of prostate pain, by tactile allodynia behavioral testing and flow cytometry. In tandem with increased CD4+IL17A+ T-cells upon EAP induction, prophylactic treatment with an anti-IL17 antibody one-day prior to EAP induction prevented the onset of pelvic pain. Therapeutic blockade of IL17 did not reverse pain symptoms indicating that IL17 is essential for development but not maintenance of chronic pain in EAP. Furthermore we identified a cytokine, IL7, to be associated with increased symptom severity in CPPS patients and is increased in patient prostatic secretions and the prostates of EAP mice. IL7 is fundamental to development of IL17 producing cells and plays a role in maturation of auto-reactive T-cells, it is also associated with autoimmune disorders including multiple sclerosis and type-1 diabetes. More recently a growing body of research has pointed to IL17’s role in development of neuropathic and chronic pain. This report presents novel data on the role of CD4+IL17+ T-cells in development and maintenance of pain in EAP and CPPS. PMID:25933188

Folate hydrolase (prostate-specific membrane [corrected] antigen) 1 expression in bladder cancer subtypes and associated tumor neovasculature.

PubMed

Samplaski, Mary K; Heston, Warren; Elson, Paul; Magi-Galluzzi, Cristina; Hansel, Donna E

2011-11-01

Folate hydrolase (prostate-specific antigen) 1 (FH(PSA)1), also known as prostate-specific membrane antigen (PSMA), is a transmembrane receptor expressed on prostate cancer cells that correlates with a more aggressive phenotype. Recent studies have demonstrated FH(PSA)1 expression in numerous benign and malignant tissue types, as well as the malignant neovasculature. As FH(PSA)1 represents a diagnostic immunomarker for prostate cancer, we explored its expression pattern in various subtypes of bladder cancer. Immunohistochemical analysis (IHC) of FH(PSA)1 was performed using tissue microarrays constructed from 167 bladder cancers, including 96 urothelial carcinomas (UCCs), 37 squamous cell carcinomas, 17 adenocarcinomas and 17 small cell carcinomas. We used a FH(PSA)1 monoclonal antibody obtained from Dako (clone 3E6, dilution 1:100), which recognizes the epitope present in the 57-134 amino acid region of the extracellular portion of the PSMA molecule. Intensity of IHC staining was scored as 0 (no expression) to 3+ (strong expression), with 2-3+ IHC considered a positive result. FH(PSA)1 demonstrated expression in a subset of bladder cancers and was most common in small cell carcinoma (3/17; 18%), with concurrent expression in non-small cell components in a subset of cases (2/6). FH(PSA)1 expression was less frequent in UCC (3/96; 3%) and adenocarcinoma (2/17; 12%). None of the squamous cell carcinomas demonstrated tumor cell expression of FH(PSA)1. However, all bladder cancers examined expressed FH(PSA)1 in the tumor vasculature, suggesting a potential role for this molecule in mediating new vessel ingrowth. FH(PSA)1 may occasionally be expressed in various subtypes of bladder cancer. These findings suggest cautious use of FH(PSA)1 as a diagnostic marker for prostatic tissue invading the bladder. The finding of FH(PSA)1 in the bladder cancer neovasculature suggests that this molecule may promote tumor growth and may represent a potential new vascular target in this disease.

About the Prostate and Urologic Cancer Research Group | Division of Cancer Prevention

Cancer.gov

The Prostate and Urologic Cancer Research Group conducts and supports research on prostate and bladder cancers, and new approaches to clinical prevention studies including cancer immunoprevention. The group develops, implements and monitors research efforts in chemoprevention, nutrition, genetic, and immunologic interventions, screening, early detection and other prevention

The Function of Neuroendocrine Cells in Prostate Cancer

DTIC Science & Technology

2014-04-01

cells were sorted based on HLA + RFP+ GFP+ and further divided into CD56+/- fractions and transplanted into recipient mice. (C) Tumors formed...in Prostate Cancer PRINCIPAL INVESTIGATOR: Jiaoti Huang CONTRACTING ORGANIZATION : REPORT DATE: April 2014 TYPE OF REPORT... ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBER University of California Los Angeles Los Angeles, CA 90095

The Mediterranean Diet Reduces the Risk and Mortality of the Prostate Cancer: A Narrative Review

PubMed Central

Capurso, Cristiano; Vendemiale, Gianluigi

2017-01-01

Prostate cancer is the second most common cancer in the world among men, and is the fifth most common cause of cancer death among men. The aim of our review was to analyze observational and case–control studies to point out the effects of overweight and diets components on the cancer risk, particularly on risk of prostate cancer, and the effect of the Mediterranean diet (MD) on the reduction of risk and mortality of prostate cancer. It is known that incidence and progression of cancer is multifactorial. Cancer of the large bowel, breast, endometrium, and prostate are due also to a high body mass index and to high consumption of high carcinogenic dietary factors, as red and processed meat or saturated fats rich foods, and to a low consumption of vegetables and fruits. Previous meta-analysis suggested that high adherence to diet model based on the traditional MD pattern gives a significant protection from incidence and mortality of cancer of all types. The main component of the MD is olive oil, consumed in high amount by Mediterranean basin populations. In addition, phenolic compounds exert some strong chemo-preventive effects, which are due to several mechanisms, including both antioxidant effects and actions on cancer cell signaling and cell cycle progression and proliferation. The protective effect of the MD against the prostate cancer is also due to the high consumption of tomato sauce. Lycopene is the most relevant functional component in tomatoes; after activating by the cooking of tomato sauce, it exerts antioxidant properties by acting in the modulation of downregulation mechanisms of the inflammatory response. MD, therefore, represents a healthy dietary pattern in the context of a healthy lifestyle habits. In conclusion, our narrative review allows us to reaffirm how nutritional factors play an important role in cancer initiation and development, and how a healthy dietary pattern represented by MD and its components, especially olive oil, could exert a protective role by the development and progression of prostate cancer. PMID:28884114

SU-C-210-02: Impact of Intrafractional Motion On TomoTherapy Stereotactic Body Radiotherapy (SBRT) 4D Dosimetry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lian, J; Matney, J; Chao, E

2015-06-15

Purpose: TomoTherapy treatment has unique challenges in handling intrafractional motion compared to conventional LINAC. This study is aimed to gain a realistic and quantitative understanding of motion impact on TomoTherapy SBRT treatment of lung and prostate cancer patients. Methods: A 4D dose engine utilizing GPUs and including motion during treatment was developed for the efficient simulation of TomoTherapy delivered dosimetry. Two clinical CyberKnife lung cases with respiratory motion tracking and two prostate cases with a slower non-periodical organ motion treated by LINAC plus Calypso tracking were used in the study. For each disease site, one selected case has an averagemore » motion (6mm); the other has a large motion (10mm for lung and 15mm for prostate). SBRT of lung and prostate cases were re-planned on TomoTherapy with 12 Gyx4 fractions and 7Gyx5 fractions, respectively, all with 95% PTV coverage. Each case was planned with 4 jaw settings: 1) conventional 1cm static, 2) 2.5cm static, 3) 2.5cm dynamic, and 4) 5cm dynamic. The intrafractional rigid motion of the target was applied in the dose calculation of individual fractions of each plan and total dose was accumulated from multiple fractions. Results: For 1cm static jaw plans with motions applied, PTV coverage is related to motion type and amplitude. For SBRT patients with average motion (6mm), the PTV coverage remains > 95% for lung case and 74% for prostate case. For cases with large motion, PTV coverage drops to 61% for lung SBRT and 49% for prostate SBRT. Plans with other jaws improve uniformity of moving target, but still suffer from poor PTV coverage (< 70%). Conclusion: TomoTherapy lung SBRT is less motion-impacted when average amplitude of respiratory-induced intrafractional motion is present (6mm). When motion is large and/or non-periodic (prostate), all studied plans lead to significantly decreased target coverage in actual delivered dosimetry.« less

Java Web Start based software for automated quantitative nuclear analysis of prostate cancer and benign prostate hyperplasia.

PubMed

Singh, Swaroop S; Kim, Desok; Mohler, James L

2005-05-11

Androgen acts via androgen receptor (AR) and accurate measurement of the levels of AR protein expression is critical for prostate research. The expression of AR in paired specimens of benign prostate and prostate cancer from 20 African and 20 Caucasian Americans was compared to demonstrate an application of this system. A set of 200 immunopositive and 200 immunonegative nuclei were collected from the images using a macro developed in Image Pro Plus. Linear Discriminant and Logistic Regression analyses were performed on the data to generate classification coefficients. Classification coefficients render the automated image analysis software independent of the type of immunostaining or image acquisition system used. The image analysis software performs local segmentation and uses nuclear shape and size to detect prostatic epithelial nuclei. AR expression is described by (a) percentage of immunopositive nuclei; (b) percentage of immunopositive nuclear area; and (c) intensity of AR expression among immunopositive nuclei or areas. The percent positive nuclei and percent nuclear area were similar by race in both benign prostate hyperplasia and prostate cancer. In prostate cancer epithelial nuclei, African Americans exhibited 38% higher levels of AR immunostaining than Caucasian Americans (two sided Student's t-tests; P < 0.05). Intensity of AR immunostaining was similar between races in benign prostate. The differences measured in the intensity of AR expression in prostate cancer were consistent with previous studies. Classification coefficients are required due to non-standardized immunostaining and image collection methods across medical institutions and research laboratories and helps customize the software for the specimen under study. The availability of a free, automated system creates new opportunities for testing, evaluation and use of this image analysis system by many research groups who study nuclear protein expression.

Non-pharmacological interventions for treating chronic prostatitis/chronic pelvic pain syndrome.

PubMed

Franco, Juan Va; Turk, Tarek; Jung, Jae Hung; Xiao, Yu-Tian; Iakhno, Stanislav; Garrote, Virginia; Vietto, Valeria

2018-01-26

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common disorder in which the two main clinical features are pelvic pain and lower urinary tract symptoms. There are currently many approaches for its management, using both pharmacological and non-pharmacological interventions. The National Institute of Health - Chronic Prostatitis Symptom Index (NIH-CPSI) score is a validated measure commonly used to measure CP/CPPS symptoms. To assess the effects of non-pharmacological therapies for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). We performed a comprehensive search using multiple databases, trial registries, grey literature and conference proceedings with no restrictions on the language of publication or publication status. The date of the latest search of all databases was August 2017. We included randomised controlled trials. Inclusion criteria were men with a diagnosis of CP/CPPS. We included all available non-pharmacological interventions. Two review authors independently classified studies and abstracted data from the included studies, performed statistical analyses and rated quality of evidence (QoE) according to the GRADE methods. We included 38 unique studies with 3290 men with CP/CPPS across 23 comparisons.1. Acupuncture: (three studies, 204 participants) based on short-term follow-up, acupuncture reduces prostatitis symptoms in an appreciable number of participants compared with sham procedure (mean difference (MD) in total NIH-CPSI score -5.79, 95% confidence interval (CI) -7.32 to -4.26, high QoE). Acupuncture likely results in little to no difference in adverse events (moderate QoE). It probably also decreases prostatitis symptoms compared with standard medical therapy in an appreciable number of participants (MD -6.05, 95% CI -7.87 to -4.24, two studies, 78 participants, moderate QoE).2. Circumcision: (one study, 713 participants) based on short-term follow-up, early circumcision probably decreases prostatitis symptoms slightly (NIH-CPSI score MD -3.00, 95% CI -3.82 to -2.18, moderate QoE) and may not be associated with a greater incidence of adverse events compared with control (a waiting list to be circumcised, low QoE).3. Electromagnetic chair: (two studies, 57 participants) based on short-term follow-up, we are uncertain of the effects of the use of an electromagnetic chair on prostatitis symptoms. It may be associated with a greater incidence of adverse events compared with sham procedure (low to very low QoE).4. Lifestyle modifications: (one study, 100 participants) based on short-term follow-up, lifestyle modifications may be associated with a greater improvement in prostatitis symptoms in an appreciable number of participants compared with control (risk ratio (RR) for improvement in NIH-CPSI scores 3.90, 95% CI 2.20 to 6.92, very low QoE). We found no information regarding adverse events.5. Physical activity: (one study, 85 participants) based on short-term follow-up, a physical activity programme may cause a small reduction in prostatitis symptoms compared with control (NIH-CPSI score MD -2.50, 95% CI -4.69 to -0.31, low QoE). We found no information regarding adverse events.6. Prostatic massage: (two studies, 115 participants) based on short-term follow-up, we are uncertain whether the prostatic massage reduces or increases prostatitis symptoms compared with control (very low QoE). We found no information regarding adverse events.7. Extracorporeal shockwave therapy: (three studies, 157 participants) based on short-term follow-up, extracorporeal shockwave therapy reduces prostatitis symptoms compared with control (NIH-CPSI score MD -6.18, 95% CI -7.46 to -4.89, high QoE). These results may not be sustained at medium-term follow-up (low QoE). This treatment may not be associated with a greater incidence of adverse events (low QoE).8. Transrectal thermotherapy compared to medical therapy: (two studies, 237 participants) based on short-term follow-up, transrectal thermotherapy alone or in combination with medical therapy may decrease prostatitis symptoms slightly when compared with medical therapy alone (NIH-CPSI score MD -2.50, 95% CI -3.82 to -1.18, low QoE). One included study reported that participants may experience transient adverse events.9. Other interventions: there is uncertainty about the effects of other interventions included in this review. We found no information regarding psychological support or prostatic surgery. Some of the interventions can decrease prostatitis symptoms in an appreciable number without a greater incidence of adverse events. The QoE was mostly low. Future clinical trials should include a full report of their methods including adequate masking, consistent assessment of all patient-important outcomes including potential treatment-related adverse events and appropriate sample sizes.

International Prostate Symptom Score is a predictive factor of lower urinary tract symptoms after radical prostatectomy.

PubMed

Bayoud, Younes; de la Taille, Alexandre; Ouzzane, Adil; Ploussard, Guillaume; Allory, Yves; Yiou, René; Vordos, Dimitri; Hoznek, Andras; Salomon, Laurent

2015-03-01

To evaluate the impact of radical prostatectomy on lower urinary tract symptoms by using the International Prostate Symptom Score and International Prostate Symptom Score quality of life. The present prospective study comprised 804 patients having localized prostate cancer who underwent radical prostatectomy. International Prostate Symptom Score and International Prostate Symptom Score quality of life were recorded preoperatively, and at 1, 3, 6, 12 and 24 months. Two study groups were considered: group 1 included patients with International Prostate Symptom Score ≤7 (mild) and group 2 included patients with International Prostate Symptom Score ≥8 (moderate to severe). Student's t-test and logistic regression were carried out to detect a predictive factor of International Prostate Symptom Score ≤7 at 24 months. The mean International Prostate Symptom Score was 5.58 ± 6.6, 11.12 ± 7.1 and 7.62 ± 6 at baseline, 1 month and 3 months, respectively (P <0.0001). The mean quality of life score showed the same evolution with a significant difference at 1 and 3 months. The mean International Prostate Symptom Score was initially 1.57 ± 1.9 in group 1 and 13.51 ± 5.5 in group 2 (P <0.0001), evolving to 3.41 ± 3.1 and 7.69 ± 5.8 at 24 months (P <0.0001), respectively. The mean quality of life score was significantly different between the groups initially, and at 6 and 12 months with P <0.0001, P = 0.005 and P = 0.02, respectively. The multivariate logistic regression showed that age, prostate volume and preoperative International Prostate Symptom Score were independent predictive factors of International Prostate Symptom Score ≤7 at 24 months (P <0.0001). In group 2, 47 patients (17%) had an International Prostate Symptom Score ≥8 at 24 months, 15 of them (32%) having a QoL score ≥3. The present study shows the beneficial impact of radical prostatectomy on lower urinary tract symptoms. However, a proportion of patients with a baseline International Prostate Symptom Score ≥8 maintain the same score at 24 months, with worsening in quality of life score in one-third of them. © 2015 The Japanese Urological Association.

Differential retention of alpha-vitamin E is correlated with its transporter gene expression and growth inhibition efficacy in prostate cancer cells.

PubMed

Ni, Jing; Pang, See-Too; Yeh, Shuyuan

2007-04-01

Epidemiological studies showed Vit E has protective effects against prostate cancer (PCa). Interestingly, different prostate cancer cells have different sensitivity to alpha-Vit E or VES treatment. The goal of this study is to determine whether cellular Vit E bioavailability and its transport proteins are important contributing factors. alpha-Vit E and its ester form, VES, were used to treat prostate cancer LNCaP, PC3, and DU145 cells, and their growth rates were determined by MTT assay. Cellular levels of Vit E were quantified using HPLC as the index of bioavailability. The expression levels of Vit E transport proteins were determined by real-time PCR. Among these PCa cells, only LNCaP cells were sensitive to 20 microM alpha-Vit E treatment, while both LNCaP and PC3 cells were sensitive to 20 microM VES treatment. Coordinately, cellular levels of alpha-Vit E and VES positively correlated to their inhibitory effects. Further study found expression levels of Vit E transport proteins, including tocopherol associated protein (TAP), scavenger receptor class B type I (SR-BI), alpha-tocopherol transfer protein (TTP), and ATP binding cassette transporter A1 (ABCA1), were different in various PCa cells, which may contribute to cellular Vit E bioavailability. This notion is further supported by the findings that overexpression or knockdown of TTP could coordinately alter cellular alpha-Vit E levels in PCa cells. Antiproliferative efficacy of alpha-Vit E is correlated with its cellular bioavailability in PCa cells. Modulating the expression of the efflux or influx transporters could sensitize the growth inhibition efficacy of Vit E in prostate cancer cells.

Long non-coding RNAs and sulforaphane: a target for chemoprevention and suppression of prostate cancer

PubMed Central

Beaver, Laura M.; Kuintzle, Rachael; Buchanan, Alex; Wiley, Michelle W.; Glasser, Sarah T.; Wong, Carmen P.; Johnson, Gavin S.; Chang, Jeff H.; Löhr, Christiane V.; Williams, David E.; Dashwood, Roderick H.; Hendrix, David A.; Ho, Emily

2017-01-01

Long non-coding RNAs (lncRNAs) have emerged as important in cancer development and progression. The impact of diet on lncRNA expression is largely unknown. Sulforaphane (SFN), obtained from vegetables like broccoli, can prevent and suppress cancer formation. Here we tested the hypothesis that SFN attenuates the expression of cancer-associated lncRNAs. We analyzed whole genome RNA-sequencing data of normal human prostate epithelial cells and prostate cancer cells treated with 15 μM SFN or DMSO. SFN significantly altered expression of ~100 lncRNAs in each cell type, and normalized the expression of some lncRNAs that were differentially expressed in cancer cells. SFN-mediated alterations in lncRNA expression correlated with genes that regulate cell cycle, signal transduction, and metabolism. LINC01116 was functionally investigated because it was overexpressed in several cancers, and was transcriptionally repressed after SFN treatment. Knockdown of LINC01116 with siRNA decreased proliferation of prostate cancer cells, and significantly upregulated several genes including GAPDH (regulates glycolysis), MAP1LC3B2 (autophagy) and H2AFY (chromatin structure). A 4-fold decrease in the ability of the cancer cells to form colonies was found when the LINC01116 gene was disrupted through a CRISPR/CAS9 method, further supporting an oncogenic function for LINC01116 in PC-3 cells.. We identified a novel isoform of LINC01116 and bioinformatically investigated the possibility that LINC01116 could interact with target genes via ssRNA:dsDNA triplexes. Our data reveal that chemicals from the diet can influence the expression of functionally important lncRNAs, and suggest a novel mechanism by which SFN may prevent and suppress prostate cancer. PMID:28131897

Long noncoding RNAs and sulforaphane: a target for chemoprevention and suppression of prostate cancer.

PubMed

Beaver, Laura M; Kuintzle, Rachael; Buchanan, Alex; Wiley, Michelle W; Glasser, Sarah T; Wong, Carmen P; Johnson, Gavin S; Chang, Jeff H; Löhr, Christiane V; Williams, David E; Dashwood, Roderick H; Hendrix, David A; Ho, Emily

2017-04-01

Long noncoding RNAs (lncRNAs) have emerged as important in cancer development and progression. The impact of diet on lncRNA expression is largely unknown. Sulforaphane (SFN), obtained from vegetables like broccoli, can prevent and suppress cancer formation. Here we tested the hypothesis that SFN attenuates the expression of cancer-associated lncRNAs. We analyzed whole-genome RNA-sequencing data of normal human prostate epithelial cells and prostate cancer cells treated with 15 μM SFN or dimethylsulfoxide. SFN significantly altered expression of ~100 lncRNAs in each cell type and normalized the expression of some lncRNAs that were differentially expressed in cancer cells. SFN-mediated alterations in lncRNA expression correlated with genes that regulate cell cycle, signal transduction and metabolism. LINC01116 was functionally investigated because it was overexpressed in several cancers, and was transcriptionally repressed after SFN treatment. Knockdown of LINC01116 with siRNA decreased proliferation of prostate cancer cells and significantly up-regulated several genes including GAPDH (regulates glycolysis), MAP1LC3B2 (autophagy) and H2AFY (chromatin structure). A four-fold decrease in the ability of the cancer cells to form colonies was found when the LINC01116 gene was disrupted through a CRISPR/CAS9 method, further supporting an oncogenic function for LINC01116 in PC-3 cells. We identified a novel isoform of LINC01116 and bioinformatically investigated the possibility that LINC01116 could interact with target genes via ssRNA:dsDNA triplexes. Our data reveal that chemicals from the diet can influence the expression of functionally important lncRNAs, and suggest a novel mechanism by which SFN may prevent and suppress prostate cancer. Published by Elsevier Inc.

Computational Reconstruction of NFκB Pathway Interaction Mechanisms during Prostate Cancer

PubMed Central

Börnigen, Daniela; Tyekucheva, Svitlana; Wang, Xiaodong; Rider, Jennifer R.; Lee, Gwo-Shu; Mucci, Lorelei A.; Sweeney, Christopher; Huttenhower, Curtis

2016-01-01

Molecular research in cancer is one of the largest areas of bioinformatic investigation, but it remains a challenge to understand biomolecular mechanisms in cancer-related pathways from high-throughput genomic data. This includes the Nuclear-factor-kappa-B (NFκB) pathway, which is central to the inflammatory response and cell proliferation in prostate cancer development and progression. Despite close scrutiny and a deep understanding of many of its members’ biomolecular activities, the current list of pathway members and a systems-level understanding of their interactions remains incomplete. Here, we provide the first steps toward computational reconstruction of interaction mechanisms of the NFκB pathway in prostate cancer. We identified novel roles for ATF3, CXCL2, DUSP5, JUNB, NEDD9, SELE, TRIB1, and ZFP36 in this pathway, in addition to new mechanistic interactions between these genes and 10 known NFκB pathway members. A newly predicted interaction between NEDD9 and ZFP36 in particular was validated by co-immunoprecipitation, as was NEDD9's potential biological role in prostate cancer cell growth regulation. We combined 651 gene expression datasets with 1.4M gene product interactions to predict the inclusion of 40 additional genes in the pathway. Molecular mechanisms of interaction among pathway members were inferred using recent advances in Bayesian data integration to simultaneously provide information specific to biological contexts and individual biomolecular activities, resulting in a total of 112 interactions in the fully reconstructed NFκB pathway: 13 (11%) previously known, 29 (26%) supported by existing literature, and 70 (63%) novel. This method is generalizable to other tissue types, cancers, and organisms, and this new information about the NFκB pathway will allow us to further understand prostate cancer and to develop more effective prevention and treatment strategies. PMID:27078000

Predictors of Medicare costs in elderly beneficiaries with breast, colorectal, lung, or prostate cancer.

PubMed

Penberthy, L; Retchin, S M; McDonald, M K; McClish, D K; Desch, C E; Riley, G F; Smith, T J; Hillner, B E; Newschaffer, C J

1999-07-01

Determining the apportionment of costs of cancer care and identifying factors that predict costs are important for planning ethical resource allocation for cancer care, especially in markets where managed care has grown. This study linked tumor registry data with Medicare administrative claims to determine the costs of care for breast, colorectal, lung and prostate cancers during the initial year subsequent to diagnosis, and to develop models to identify factors predicting costs. Patients with a diagnosis of breast (n = 1,952), colorectal (n = 2,563), lung (n = 3,331) or prostate cancer (n = 3,179) diagnosed from 1985 through 1988. The average costs during the initial treatment period were $12,141 (s.d. = $10,434) for breast cancer, $24,910 (s.d. = $14,870) for colorectal cancer, $21,351 (s.d. = $14,813) for lung cancer, and $14,361 (s.d. = $11,216) for prostate cancer. Using least squares regression analysis, factors significantly associated with cost included comorbidity, hospital length of stay, type of therapy, and ZIP level income for all four cancer sites. Access to health care resources was variably associated with costs of care. Total R2 ranged from 38% (prostate) to 49% (breast). The prediction error for the regression models ranged from < 1% to 4%, by cancer site. Linking administrative claims with state tumor registry data can accurately predict costs of cancer care during the first year subsequent to diagnosis for cancer patients. Regression models using both data sources may be useful to health plans and providers and in determining appropriate prospective reimbursement for cancer, particularly with increasing HMO penetration and decreased ability to capture complete and accurate utilization and cost data on this population.

PDE5 inhibitors blunt inflammation in human BPH: a potential mechanism of action for PDE5 inhibitors in LUTS.

PubMed

Vignozzi, Linda; Gacci, Mauro; Cellai, Ilaria; Morelli, Annamaria; Maneschi, Elena; Comeglio, Paolo; Santi, Raffaella; Filippi, Sandra; Sebastianelli, Arcangelo; Nesi, Gabriella; Serni, Sergio; Carini, Marco; Maggi, Mario

2013-09-01

Metabolic syndrome (MetS) and benign prostate hyperplasia (BPH)/low urinary tract symptoms (LUTS) are often comorbid. Chronic inflammation is one of the putative links between these diseases. Phosphodiesterase type 5 inhibitors (PDE5i) are recognized as an effective treatment of BPH-related LUTS. One proposed mechanism of action of PDE5 is the inhibition of intraprostatic inflammation. In this study we investigate whether PDE5i could blunt inflammation in the human prostate. Evaluation of the effect of tadalafil and vardenafil on secretion of interleukin 8 (IL-8, a surrogate marker of prostate inflammation) by human myofibroblast prostatic cells (hBPH) exposed to different inflammatory stimuli. We preliminary evaluate histological features of prostatic inflammatory infiltrates in BPH patients enrolled in a randomized, double bind, placebo controlled study aimed at investigating the efficacy of vardenafil (10 mg/day, for 12 weeks) on BPH/LUTS. In vitro treatment with tadalafil or vardenafil on hBPH reduced IL-8 secretion induced by either TNFα or metabolic factors, including oxidized low-density lipoprotein, oxLDL, to the same extent as a PDE5-insensitive PKG agonist Sp-8-Br-PET-cGMP. These effects were reverted by the PKG inhibitor KT5823, suggesting a cGMP/PKG-dependency. Treatment with tadalafil or vardenafil significantly suppressed oxLDL receptor (LOX-1) expression. Histological evaluation of anti-CD45 staining (CD45 score) in prostatectomy specimens of BPH patients showed a positive association with MetS severity. Reduced HDL-cholesterol and elevated triglycerides were the only MetS factors significantly associated with CD45 score. In the MetS cohort there was a significant lower CD45 score in the vardenafil-arm versus the placebo-one. © 2013 Wiley Periodicals, Inc.

Inverse Regulation of DHT Synthesis Enzymes 5α-Reductase Types 1 and 2 by the Androgen Receptor in Prostate Cancer.

PubMed

Audet-Walsh, Étienne; Yee, Tracey; Tam, Ingrid S; Giguère, Vincent

2017-04-01

5α-Reductase types 1 and 2, encoded by SRD5A1 and SRD5A2, are the two enzymes that can catalyze the conversion of testosterone to dihydrotestosterone, the most potent androgen receptor (AR) agonist in prostate cells. 5α-Reductase type 2 is the predominant isoform expressed in the normal prostate. However, its expression decreases during prostate cancer (PCa) progression, whereas SRD5A1 increases, and the mechanism underlying this transcriptional regulatory switch is still unknown. Interrogation of SRD5A messenger RNA expression in three publicly available data sets confirmed that SRD5A1 is increased in primary and metastatic PCa compared with nontumoral prostate tissues, whereas SRD5A2 is decreased. Activation of AR, a major oncogenic driver of PCa, induced the expression of SRD5A1 from twofold to fourfold in three androgen-responsive PCa cell lines. In contrast, AR repressed SRD5A2 expression in this context. Chromatin-immunoprecipitation studies established that AR is recruited to both SRD5A1 and SRD5A2 genes following androgen stimulation but initiates transcriptional activation only at SRD5A1 as monitored by recruitment of RNA polymerase II and the presence of the H3K27Ac histone mark. Furthermore, we showed that the antiandrogens bicalutamide and enzalutamide block the AR-mediated regulation of both SRD5A1 and SRD5A2, highlighting an additional mechanism explaining their beneficial effects in patients. In summary, we identified an AR-dependent transcriptional regulation that explains the differential expression of 5α-reductase types 1 and 2 during PCa progression. Our work thus defines a mechanism by which androgens control their own synthesis via differential regulatory control of the expression of SRD5A1 and SRD5A2. Copyright © 2017 Endocrine Society.

Proliferation of prostate cancer cells and activity of neutral endopeptidase is regulated by bombesin and IL-1beta with IL-1beta acting as a modulator of cellular differentiation.

PubMed

Albrecht, Martin; Doroszewicz, Jolanta; Gillen, Sonja; Gomes, Iara; Wilhelm, Beate; Stief, Thomas; Aumüller, Gerhard

2004-01-01

Neutral endopeptidase (NEP) is a cell-surface bound enzyme that cleaves and inactivates neuropeptides such as bombesin and substance P and is involved in the transition from hormonally regulated androgen-dependent prostate cancer (PC) to androgen-independent PC. Neuropeptides are implicated in growth regulation of different cell types and function as transmitters between the neuroendocrine and the immune system. NEP-expression, enzymatic activity of the membrane bound protein, cell proliferation, procalcitonin (PCT) production, and secretion as well as changes in cell morphology of prostatic cells were evaluated after treatment with the immunomodulatory cytokine interleukin-1beta (IL-1beta), neuropeptides (bombesin, substance P), and neuropeptide-conditioned media derived from a human neuroendocrine cell line. Incubation of LNCaP tumor cells with IL-1beta resulted in a diminished proliferative activity, induction of neurite-like outgrowth which was accompanied by the formation of tubular-type mitochondria typical for neuronal/neuroendocrine cells, and an increased production and secretion of PCT. Conversely, proliferation of prostatic stromal cells was enhanced by the cytokine coming along with an increased number of Golgi-apparatuses and ER-cisternae. Bombesin had an antimitotic effect on LNCaP, but not on stromal cells. Substance P did not influence the growth of any of the cell types investigated, whereas neuropeptide-conditioned media exerted a slightly mitogenic effect on both cell types. The activity of LNCaP cell-surface bound NEP was enhanced by bombesin, but was diminished by substance P and neuropeptide-conditioned media. Proliferation and activity of neuropeptide degrading NEP is regulated differently by immunomodulatory substances in PC cells and cells derived from the prostatic stroma with IL-1beta being a potent modulator of cellular differentiation and a potential target for anticancer drug design in PC cells. Copyright 2003 Wiley-Liss, Inc.

The Diagnostic Performance of Multiparametric Magnetic Resonance Imaging to Detect Significant Prostate Cancer.

PubMed

Thompson, J E; van Leeuwen, P J; Moses, D; Shnier, R; Brenner, P; Delprado, W; Pulbrook, M; Böhm, M; Haynes, A M; Hayen, A; Stricker, P D

2016-05-01

We assess the accuracy of multiparametric magnetic resonance imaging for significant prostate cancer detection before diagnostic biopsy in men with an abnormal prostate specific antigen/digital rectal examination. A total of 388 men underwent multiparametric magnetic resonance imaging, including T2-weighted, diffusion weighted and dynamic contrast enhanced imaging before biopsy. Two radiologists used PI-RADS to allocate a score of 1 to 5 for suspicion of significant prostate cancer (Gleason 7 with more than 5% grade 4). PI-RADS 3 to 5 was considered positive. Transperineal template guided mapping biopsy of 18 regions (median 30 cores) was performed with additional manually directed cores from magnetic resonance imaging positive regions. The anatomical location, size and grade of individual cancer areas in the biopsy regions (18) as the primary outcome and in prostatectomy specimens (117) as the secondary outcome were correlated to the magnetic resonance imaging positive regions. Of the 388 men who were enrolled in the study 344 were analyzed. Multiparametric magnetic resonance imaging was positive in 77.0% of patients, 62.5% had prostate cancer and 41.6% had significant prostate cancer. The detection of significant prostate cancer by multiparametric magnetic resonance imaging had a sensitivity of 96%, specificity of 36%, negative predictive value of 92% and positive predictive value of 52%. Adding PI-RADS to the multivariate model, including prostate specific antigen, digital rectal examination, prostate volume and age, improved the AUC from 0.776 to 0.879 (p <0.001). Anatomical concordance analysis showed a low mismatch between the magnetic resonance imaging positive regions and biopsy positive regions (4 [2.9%]), and the significant prostate cancer area in the radical prostatectomy specimen (3 [3.3%]). In men with an abnormal prostate specific antigen/digital rectal examination, multiparametric magnetic resonance imaging detected significant prostate cancer with an excellent negative predictive value and moderate positive predictive value. The use of multiparametric magnetic resonance imaging to diagnose significant prostate cancer may result in a substantial number of unnecessary biopsies while missing a minimum of significant prostate cancers. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Online updating of context-aware landmark detectors for prostate localization in daily treatment CT images

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dai, Xiubin; Gao, Yaozong; Shen, Dinggang, E-mail: dgshen@med.unc.edu

2015-05-15

Purpose: In image guided radiation therapy, it is crucial to fast and accurately localize the prostate in the daily treatment images. To this end, the authors propose an online update scheme for landmark-guided prostate segmentation, which can fully exploit valuable patient-specific information contained in the previous treatment images and can achieve improved performance in landmark detection and prostate segmentation. Methods: To localize the prostate in the daily treatment images, the authors first automatically detect six anatomical landmarks on the prostate boundary by adopting a context-aware landmark detection method. Specifically, in this method, a two-layer regression forest is trained as amore » detector for each target landmark. Once all the newly detected landmarks from new treatment images are reviewed or adjusted (if necessary) by clinicians, they are further included into the training pool as new patient-specific information to update all the two-layer regression forests for the next treatment day. As more and more treatment images of the current patient are acquired, the two-layer regression forests can be continually updated by incorporating the patient-specific information into the training procedure. After all target landmarks are detected, a multiatlas random sample consensus (multiatlas RANSAC) method is used to segment the entire prostate by fusing multiple previously segmented prostates of the current patient after they are aligned to the current treatment image. Subsequently, the segmented prostate of the current treatment image is again reviewed (or even adjusted if needed) by clinicians before including it as a new shape example into the prostate shape dataset for helping localize the entire prostate in the next treatment image. Results: The experimental results on 330 images of 24 patients show the effectiveness of the authors’ proposed online update scheme in improving the accuracies of both landmark detection and prostate segmentation. Besides, compared to the other state-of-the-art prostate segmentation methods, the authors’ method achieves the best performance. Conclusions: By appropriate use of valuable patient-specific information contained in the previous treatment images, the authors’ proposed online update scheme can obtain satisfactory results for both landmark detection and prostate segmentation.« less

Lack of Liver X Receptors Leads to Cell Proliferation in a Model of Mouse Dorsal Prostate Epithelial Cell

PubMed Central

Dufour, Julie; Pommier, Aurélien; Alves, Georges; De Boussac, Hugues; Lours-Calet, Corinne; Volle, David H.; Lobaccaro, Jean-Marc A.; Baron, Silvère

2013-01-01

Recent studies underline the implication of Liver X Receptors (LXRs) in several prostate diseases such as benign prostatic hyperplasia (BPH) and prostate cancer. In order to understand the molecular mechanisms involved, we derived epithelial cells from dorsal prostate (MPECs) of wild type (WT) or Lxrαβ−/− mice. In the WT MPECs, our results show that LXR activation reduces proliferation and correlates with the modification of the AKT-survival pathway. Moreover, LXRs regulate lipid homeostasis with the regulation of Abca1, Abcg1 and Idol, and, in a lesser extent, Srebp1, Fas and Acc. Conversely cells derived from Lxrαβ−/− mice show a higher basal phosphorylation and consequently activation of the survival/proliferation transduction pathways AKT and MAPK. Altogether, our data point out that the cell model we developed allows deciphering the molecular mechanisms inducing the cell cycle arrest. Besides, we show that activated LXRs regulate AKT and MAPK transduction pathways and demonstrate that LXRs could be good pharmacological targets in prostate disease such as cancer. PMID:23554947

DEPDC1 promotes cell proliferation and tumor growth via activation of E2F signaling in prostate cancer.

PubMed

Huang, Lin; Chen, Keng; Cai, Zhao-Peng; Chen, Fu-Chao; Shen, Hui-Yong; Zhao, Wei-Hua; Yang, Song-Jie; Chen, Xu-Biao; Tang, Guo-Xue; Lin, Xi

2017-08-26

DEP domain containing 1 (DEPDC1) is recently reported to be overexpressed in several types of human cancer; however the role of DEPDC1 in prostate cancer remains to be investigated. Herein, we identified that the DEPDC1 mRNA and protein expression levels were dramatically increased in prostate cancer tissues and cell lines. Overexpression of DEPDC1 promoted, but depletion of DEPDC1 inhibited cell proliferation by regulating the G1-S phase cell cycle transition. Importantly, we found that DEPDC1 was essential for the tumor growth and formation of bone metastases of prostate cancer cells in vivo. Finally, we demonstrated that DEPDC1 interacted with E2F1 and increased its transcriptional activity, leading to hyper-activation of E2F signaling in prostate cancer cells. Our findings reveal an oncogenic role of DEPDC1 in prostate cancer progression via activation of E2F signaling, and suggest DEPDC1 might be a potential therapeutic target against the disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Mithramycin A induces apoptosis by regulating the mTOR/Mcl-1/tBid pathway in androgen-independent prostate cancer cells

PubMed Central

Choi, Eun-Sun; Chung, Taeho; Kim, Jun-Sung; Lee, Hakmo; Kwon, Ki Han; Cho, Nam-Pyo; Cho, Sung-Dae

2013-01-01

Mithramycin A (Mith) is an aureolic acid-type polyketide produced by various soil bacteria of the genus Streptomyces. Mith inhibits myeloid cell leukemia-1 (Mcl-1) to induce apoptosis in prostate cancer, but the molecular mechanism underlying this process has not been fully elucidated. The aim of this study was therefore to investigate the detailed molecular mechanism related to Mith-induced apoptosis in prostate cancer cells. Mith decreased the phosphorylation of mammalian target of rapamycin (mTOR) in both cell lines overexpressing phospho-mTOR compared to RWPE-1 human normal prostate epithelial cells. Mith significantly induced truncated Bid (tBid) and siRNA-mediated knock-down of Mcl-1 increased tBid protein levels. Moreover, Mith also inhibited the phosphorylation of mTOR on serine 2448 and Mcl-1, and increased tBid protein in prostate tumors in athymic nude mice bearing DU145 cells as xenografts. Thus, Mith acts as an effective tumor growth inhibitor in prostate cancer cells through the mTOR/Mcl-1/tBid signaling pathway. PMID:24062605

Overexpression of LLT1 (OCIL, CLEC2D) on prostate cancer cells inhibits NK cell-mediated killing through LLT1-NKRP1A (CD161) interaction.

PubMed

Mathew, Stephen O; Chaudhary, Pankaj; Powers, Sheila B; Vishwanatha, Jamboor K; Mathew, Porunelloor A

2016-10-18

Prostate cancer is the most common type of cancer diagnosed and the second leading cause of cancer-related death in American men. Natural Killer (NK) cells are the first line of defense against cancer and infections. NK cell function is regulated by a delicate balance between signals received through activating and inhibitory receptors. Previously, we identified Lectin-like transcript-1 (LLT1/OCIL/CLEC2D) as a counter-receptor for the NK cell inhibitory receptor NKRP1A (CD161). Interaction of LLT1 expressed on target cells with NKRP1A inhibits NK cell activation. In this study, we have found that LLT1 was overexpressed on prostate cancer cell lines (DU145, LNCaP, 22Rv1 and PC3) and in primary prostate cancer tissues both at the mRNA and protein level. We further showed that LLT1 is retained intracellularly in normal prostate cells with minimal cell surface expression. Blocking LLT1 interaction with NKRP1A by anti-LLT1 mAb on prostate cancer cells increased the NK-mediated cytotoxicity of prostate cancer cells. The results indicate that prostate cancer cells may evade immune attack by NK cells by expressing LLT1 to inhibit NK cell-mediated cytolytic activity through LLT1-NKRP1A interaction. Blocking LLT1-NKRP1A interaction will make prostate cancer cells susceptible to killing by NK cells and therefore may be a new therapeutic option for treatment of prostate cancer.

Hyper-expression of PAX2 in human metastatic prostate tumors and its role as a cancer promoter in an in vitro invasion model.

PubMed

Ueda, Takashi; Ito, Saya; Shiraishi, Takumi; Kulkarni, Prakash; Ueno, Akihisa; Nakagawa, Hideo; Kimura, Yasunori; Hongo, Fumiya; Kamoi, Kazumi; Kawauchi, Akihiro; Miki, Tsuneharu

2013-09-01

Metastasis is a consequence of many biological events, during which cancer stem cells are shifted into a malignant state. Among these events, invasion of prostate cancer cells into host tissues is possible to be assessed by means of an in vitro invasion model, and is thought to be coupled to altered expression of membrane proteins. Dysregulated functions of the factors regulating organogenesis during embryogenesis are known to facilitate metastasis of many types of cancers. PAX2 (paired box 2) is a member of the PAX transcription factor family, which regulates prostatic ductal growth and branching in organogenesis of mammalian prostates. However, the role of PAX2 in prostate cancer development remains to be determined. PAX2 expression in human prostate cancers and normal prostate epithelium were examined by quantitative RT-PCR and immunohistochemistry. Matrigel invasion assay and a gene array analysis were performed using prostate cancer cell lines transfected with either control or PAX2 siRNA. In human prostate cancers, PAX2 was hyper-expressed in metastatic cancers, but was expressed at lower levels in non-metastatic cancers. Consistent with this, PAX2 knockdown repressed cell growth and invasion in a Matrigel invasion assay. Gene ontology analysis revealed that many cell membrane proteins were downregulated after PAX2 knockdown. Our data suggested that PAX2 hyper-expression promotes the development of the metastatic state in prostate cancer cells, presumably through upregulating the expression of cell membrane proteins. Copyright © 2013 Wiley Periodicals, Inc.

What does it cost Medicare to diagnose and treat men with localized prostate cancer in the first year?

PubMed

Mervin, Merehau C; Lowe, Anthony; Gardiner, Robert A; Smith, David P; Aitken, Joanne; Chambers, Suzanne K; Gordon, Louisa G

2017-06-01

To estimate costs on the Medicare Benefits Schedule (MBS) and the Pharmaceutical Benefits Scheme (PBS) attributable to the diagnosis and treatment of prostate cancer. We used data from a cohort study of 1064 men with localized prostate cancer recruited between 2005 and 2007 by 24 urologists across 10 sites in Queensland, Australia (ProsCan). We estimated the MBS and PBS costs attributable to prostate cancer from the date of initial appointment to 12 months after diagnosis in 2013 Australian dollars using a comparison group without prostate cancer. We used generalized linear modeling to identify key determinants of higher treatment-related costs. From the date of initial appointment to 12 months postdiagnosis, the average MBS costs attributable to prostate cancer were $9,357 (SD $191) per patient. These MBS costs were most sensitive to having private health insurance and the type of primary treatment received. The PBS costs were higher in the control group than in the ProsCan group ($5,641 vs $1,924). The costs of treating and managing prostate cancer are high and these result in a substantial financial burden for the Australian MBS. Costs attributable to prostate cancer appear to vary widely based on initial treatment and these are likely to increase with the introduction of more expensive services and pharmaceuticals. There is a pressing need for better prognostic tools to distinguish between indolent and aggressive prostate tumors to reduce potential over treatment and help ease the burden of prostate cancer. © 2017 John Wiley & Sons Australia, Ltd.

Does Inflammation Mediate the Obesity and BPH Relationship? An Epidemiologic Analysis of Body Composition and Inflammatory Markers in Blood, Urine, and Prostate Tissue, and the Relationship with Prostate Enlargement and Lower Urinary Tract Symptoms.

PubMed

Fowke, Jay H; Koyama, Tatsuki; Fadare, Oluwole; Clark, Peter E

2016-01-01

BPH is a common disease associated with age and obesity. However, the biological pathways between obesity and BPH are unknown. Our objective was to investigate biomarkers of systemic and prostate tissue inflammation as potential mediators of the obesity and BPH association. Participants included 191 men without prostate cancer at prostate biopsy. Trained staff measured weight, height, waist and hip circumferences, and body composition by bioelectric impedance analysis. Systemic inflammation was estimated by serum IL-6, IL-1β, IL-8, and TNF-α; and by urinary prostaglandin E2 metabolite (PGE-M), F2-isoprostane (F2iP), and F2-isoprostane metabolite (F2iP-M) levels. Prostate tissue was scored for grade, aggressiveness, extent, and location of inflammatory regions, and also stained for CD3 and CD20 positive lymphocytes. Analyses investigated the association between multiple body composition scales, systemic inflammation, and prostate tissue inflammation against BPH outcomes, including prostate size at ultrasound and LUTS severity by the AUA-symptom index (AUA-SI). Prostate size was significantly associated with all obesity measures. For example, prostate volume was 5.5 to 9.0 mls larger comparing men in the 25th vs. 75th percentile of % body fat, fat mass (kg) or lean mass (kg). However, prostate size was not associated with proinflammatory cytokines, PGE-M, F2iP, F2iP-M, prostate tissue inflammation scores or immune cell infiltration. In contrast, the severity of prostate tissue inflammation was significantly associated with LUTS, such that there was a 7 point difference in AUA-SI between men with mild vs. severe inflammation (p = 0.004). Additionally, men with a greater waist-hip ratio (WHR) were significantly more likely to have severe prostate tissue inflammation (p = 0.02), and a high WHR was significantly associated with moderate/severe LUTS (OR = 2.56, p = 0.03) among those participants with prostate tissue inflammation. The WHR, an estimate of centralized obesity, was associated with the severity of inflammatory regions in prostate tissue and with LUTS severity among men with inflammation. Our results suggest centralized obesity advances prostate tissue inflammation to increase LUTS severity. Clinically targeting centralized fat deposition may reduce LUTS severity. Mechanistically, the lack of a clear relationship between systemic inflammatory or oxidative stress markers in blood or urine with prostate size or LUTS suggests pathways other than systemic inflammatory signaling may link body adiposity to BPH outcomes.

Signaling networks in TMPRSS2-ERG positive prostate cancers: Do we need a Pied Piper or sharpshooter to deal with "at large" fused oncoprotein.

PubMed

Lin, X; Qureshi, M Z; Romero, M A; Yaylim, I; Arif, S; Ucak, I; Fayyaz, S; Farooqi, A A; Mansoor, Q; Ismail, M

2017-02-28

Overwhelmingly increasing scientific evidence has provided near complete resolution of prostate cancer landscape and it is now more understandable that wide ranging factors underlies its development and progression. Increasingly it is being realized that genetic/epigenetic factors, Intra-tumoral and inter-tumoral heterogeneity, loss of apoptosis, dysregulations of spatio-temporally controlled signaling cascades, Darwinian evolution in response to therapeutic pressures play instrumental role in prostate carcinogenesis. Moreover, multi-directional patterns of spread between primary tumors and metastatic sites have also been studied extensively in prostate cancer. Research over the years has gradually and systematically revealed closer association between tumor phenotype and type of gene fusion. Latest developments in deep sequencing technologies have shown that gene fusions originate in a non-random, cell type dependent manner and are much more frequent than previously surmised. These findings enabled sub-classification and categorization of seemingly identical diseases. Furthermore, research methodologies have shown that many gene fusions inform us about risk stratification and many chimeric proteins encoded by the fused genes are being studied as drug target/s. We partition this multi-component review into the molecular basis of formation of fusion transcripts, how protein network is regulated in fusion positive prostate cancer cells and therapeutic strategies which are currently being investigated to efficiently target fusion transcript and its protein product.

Quantitative volumetric imaging of normal, neoplastic and hyperplastic mouse prostate using ultrasound.

PubMed

Singh, Shalini; Pan, Chunliu; Wood, Ronald; Yeh, Chiuan-Ren; Yeh, Shuyuan; Sha, Kai; Krolewski, John J; Nastiuk, Kent L

2015-09-21

Genetically engineered mouse models are essential to the investigation of the molecular mechanisms underlying human prostate pathology and the effects of therapy on the diseased prostate. Serial in vivo volumetric imaging expands the scope and accuracy of experimental investigations of models of normal prostate physiology, benign prostatic hyperplasia and prostate cancer, which are otherwise limited by the anatomy of the mouse prostate. Moreover, accurate imaging of hyperplastic and tumorigenic prostates is now recognized as essential to rigorous pre-clinical trials of new therapies. Bioluminescent imaging has been widely used to determine prostate tumor size, but is semi-quantitative at best. Magnetic resonance imaging can determine prostate volume very accurately, but is expensive and has low throughput. We therefore sought to develop and implement a high throughput, low cost, and accurate serial imaging protocol for the mouse prostate. We developed a high frequency ultrasound imaging technique employing 3D reconstruction that allows rapid and precise assessment of mouse prostate volume. Wild-type mouse prostates were examined (n = 4) for reproducible baseline imaging, and treatment effects on volume were compared, and blinded data analyzed for intra- and inter-operator assessments of reproducibility by correlation and for Bland-Altman analysis. Examples of benign prostatic hyperplasia mouse model prostate (n = 2) and mouse prostate implantation of orthotopic human prostate cancer tumor and its growth (n =  ) are also demonstrated. Serial measurement volume of the mouse prostate revealed that high frequency ultrasound was very precise. Following endocrine manipulation, regression and regrowth of the prostate could be monitored with very low intra- and interobserver variability. This technique was also valuable to monitor the development of prostate growth in a model of benign prostatic hyperplasia. Additionally, we demonstrate accurate ultrasound image-guided implantation of orthotopic tumor xenografts and monitoring of subsequent tumor growth from ~10 to ~750 mm(3) volume. High frequency ultrasound imaging allows precise determination of normal, neoplastic and hyperplastic mouse prostate. Low cost and small image size allows incorporation of this imaging modality inside clean animal facilities, and thereby imaging of immunocompromised models. 3D reconstruction for volume determination is easily mastered, and both small and large relative changes in volume are accurately visualized. Ultrasound imaging does not rely on penetration of exogenous imaging agents, and so may therefore better measure poorly vascularized or necrotic diseased tissue, relative to bioluminescent imaging (IVIS). Our method is precise and reproducible with very low inter- and intra-observer variability. Because it is non-invasive, mouse models of prostatic disease states can be imaged serially, reducing inter-animal variability, and enhancing the power to detect small volume changes following therapeutic intervention.

Marked suppression of dihydrotestosterone in men with benign prostatic hyperplasia by dutasteride, a dual 5alpha-reductase inhibitor.

PubMed

Clark, Richard V; Hermann, David J; Cunningham, Glenn R; Wilson, Timothy H; Morrill, Betsy B; Hobbs, Stuart

2004-05-01

Dihydrotestosterone (DHT) is the primary metabolite of testosterone in the prostate and skin. Testosterone is converted to DHT by 5alpha-reductase, which exists in two isoenzyme forms (types 1 and 2). DHT is associated with development of benign prostatic hyperplasia (BPH), and reduction in its level with 5alpha-reductase inhibitors improves the symptoms associated with BPH and reduces the risk of acute urinary retention and prostate surgery. A selective inhibitor of the type 2 isoenzyme (finasteride) has been shown to decrease serum DHT by about 70%. We hypothesized that inhibition of both isoenzymes with the dual inhibitor dutasteride would more effectively suppress serum DHT levels than selective inhibition of only the type 2 isoenzyme. A total of 399 patients with BPH were randomized to receive once-daily dosing for 24 wk of dutasteride (0.01, 0.05, 0.5, 2.5, or 5.0 mg), 5 mg finasteride, or placebo. The mean percent decrease in DHT was 98.4 +/- 1.2% with 5.0 mg dutasteride and 94.7 +/- 3.3% with 0.5 mg dutasteride, significantly lower (P < 0.001) and with less variability than the 70.8 +/- 18.3% suppression observed with 5 mg finasteride. Mean testosterone levels increased but remained in the normal range for all treatment groups. Dutasteride appeared to be well tolerated with an adverse event profile similar to placebo.

The effect of a combination of prostatic massage and antibiotic plus anticongestive drugs on human semen quality and fertility.

PubMed

Homonnai, Z T; Fainman, N; Paz, G; Kraicer, P F

1979-01-01

A total of 123 patients suffering from chronic prostatitis and infertility were included in this study. No significant improvement in sperm quality was found following prostatic massage with (90 patients) or without (33) antiobiotic plus anticongestive therapy. There was no apparent change in the relative contribution on the prostate and seminal vesicle of the ejaculate, as judged by the concentration of calcium and fructose. Nor was the pregnancy rate increased. It is concluded that prostatic massage is of little or no therapeutic value in treatment of infertility.

Development of a Recombinant Multifunctional Biomacromolecule for Targeted Gene Transfer to Prostate Cancer Cells.

PubMed

Hatefi, Arash; Karjoo, Zahra; Nomani, Alireza

2017-09-11

The objective of this study was to genetically engineer a fully functional single chain fusion peptide composed of motifs from diverse biological and synthetic origins that can perform multiple tasks including DNA condensation, cell targeting, cell transfection, particle shielding from immune system and effective gene transfer to prostate tumors. To achieve the objective, a single chain biomacromolecule (vector) consisted of four repeatative units of histone H2A peptide, fusogenic peptide GALA, short elastin-like peptide, and PC-3 cell targeting peptide was designed. To examine the functionality of each motif in the vector sequence, it was characterized in terms of size and zeta potential by Zetasizer, PC-3 cell targeting and transfection by flowcytometry, IgG induction by immunogenicity assay, and PC-3 tumor transfection by quantitative live animal imaging. Overall, the results of this study showed the possibility of using genetic engineering techniques to program various functionalities into one single chain vector and create a multifunctional nonimmunogenic biomacromolecule for targeted gene transfer to prostate cancer cells. This proof-of-concept study is a significant step forward toward creating a library of vectors for targeted gene transfer to any cancer cell type at both in vitro and in vivo levels.

Regressive changes in finasteride-treated human hyperplastic prostates correlate with an upregulation of TGF-beta receptor expression.

PubMed

Sáez, C; González-Baena, A C; Japón, M A; Giráldez, J; Segura, D I; Miranda, G; Rodríguez-Vallejo, J M; González-Esteban, J; Torrubia, F

1998-10-01

Prostatic atrophy has been documented histologically as a consequence of finasteride action on human hyperplastic prostates. An increase in apoptotic rates has also been reported in androgen-deprived hyperplastic prostates. Transforming growth factor beta (TGF-beta) signaling is implicated in apoptotic cell death. TGF-betas have been detected in normal and diseased human prostate. In the normal prostate, TGF-beta acts as a predominantly negative growth regulator. TGF-beta signaling receptors TbetaRI and TbetaRII have been shown to be negatively regulated by androgens. We studied the histological changes in 9 selected finasteride-treated patients with benign prostatic hyperplasia (BPH), and analyzed the levels of expression and localization of TGF-beta receptor types TbetaRI and TbetaRII in these patients as compared to selected BPH controls. The prostatic epithelial compartment seemed to be a primary target site for finasteride action, since we observed moderate to severe glandular atrophy after 4-6 months of treatment. TGF-beta receptors were upregulated in treated cases. We assessed a twofold increase in TbetaRII mRNA levels in treated cases as compared to controls. An increase in both TbetaRI and TbetaRII at the protein level by immunostaining was observed, which also provided a helpful means for detecting glands undergoing regression. We conclude that finasteride may modulate the TGF-beta signaling system to promote changes leading to apoptosis of epithelial cells and prostatic glandular atrophy.

Escherichia coli isolates from patients with bacteremic urinary tract infection are genetically distinct from those derived from sepsis following prostate transrectal biopsy.

PubMed

Dan, Michael; Yair, Yael; Samosav, Alex; Gottesman, Tamar; Yossepowitch, Orit; Harari-Schwartz, Orna; Tsivian, Alexander; Schreiber, Rachel; Gophna, Uri

2015-01-01

Transrectal ultrasound-guided (TRUS) prostate biopsy is a very common procedure that is generally considered relatively safe. However, severe sepsis can occur after TRUS prostate biopsies, with Escherichia coli being the predominant causative agent. A common perception is that the bacteria that cause post-TRUS prostate biopsy infections originate in the urinary tract, but this view has not been adequately tested. Yet other authors believe on the basis of indirect evidence that the pathogens are introduced into the bloodstream by the biopsy needle after passage through the rectal mucosa. We compared E. coli isolates from male patients with bacteremic urinary tract infection (B-UTI) to isolates of patients with post prostate biopsy sepsis (PPBS), in terms of their sequence types, determined by multi-locus sequence typing (MLST) and their virulence markers. B-UTI isolates were much richer in virulence genes than were PPBS isolates, supporting the hypothesis that E. coli causing PPBS derive directly from the rectum. Sequence type 131 (ST131) strains and related strain from the ST131 were common (>30%) among the E. coli isolates from PPBS patients as well as from B-UTI patients and all these strains expressed extended spectrum beta-lactamases. Our finding supports the hypothesis that E. coli causing PPBS derive directly from the rectum, bypassing the urinary tract, and therefore do not require many of the virulence capabilities necessary for an E. coli strain that must persist in the urinary tract. In light of the increasing prevalence of highly resistant E. coli strains, a new approach for prevention of PPBS is urgently required. Copyright © 2015. Published by Elsevier GmbH.

Rare ADAR and RNASEH2B variants and a type I interferon signature in glioma and prostate carcinoma risk and tumorigenesis.

PubMed

Beyer, Ulrike; Brand, Frank; Martens, Helge; Weder, Julia; Christians, Arne; Elyan, Natalie; Hentschel, Bettina; Westphal, Manfred; Schackert, Gabriele; Pietsch, Torsten; Hong, Bujung; Krauss, Joachim K; Samii, Amir; Raab, Peter; Das, Anibh; Dumitru, Claudia A; Sandalcioglu, I Erol; Hakenberg, Oliver W; Erbersdobler, Andreas; Lehmann, Ulrich; Reifenberger, Guido; Weller, Michael; Reijns, Martin A M; Preller, Matthias; Wiese, Bettina; Hartmann, Christian; Weber, Ruthild G

2017-12-01

In search of novel germline alterations predisposing to tumors, in particular to gliomas, we studied a family with two brothers affected by anaplastic gliomas, and their father and paternal great-uncle diagnosed with prostate carcinoma. In this family, whole-exome sequencing yielded rare, simultaneously heterozygous variants in the Aicardi-Goutières syndrome (AGS) genes ADAR and RNASEH2B co-segregating with the tumor phenotype. AGS is a genetically induced inflammatory disease particularly of the brain, which has not been associated with a consistently increased cancer risk to date. By targeted sequencing, we identified novel ADAR and RNASEH2B variants, and a 3- to 17-fold frequency increase of the AGS mutations ADAR,c.577C>G;p.(P193A) and RNASEH2B,c.529G>A;p.(A177T) in the germline of familial glioma patients as well as in test and validation cohorts of glioblastomas and prostate carcinomas versus ethnicity-matched controls, whereby rare RNASEH2B variants were significantly more frequent in familial glioma patients. Tumors with ADAR or RNASEH2B variants recapitulated features of AGS, such as calcification and increased type I interferon expression. Patients carrying ADAR or RNASEH2B variants showed upregulation of interferon-stimulated gene (ISG) transcripts in peripheral blood as seen in AGS. An increased ISG expression was also induced by ADAR and RNASEH2B variants in tumor cells and was blocked by the JAK inhibitor Ruxolitinib. Our data implicate rare variants in the AGS genes ADAR and RNASEH2B and a type I interferon signature in glioma and prostate carcinoma risk and tumorigenesis, consistent with a genetic basis underlying inflammation-driven malignant transformation in glioma and prostate carcinoma development.

A single microfocus (5% or less) of Gleason 6 prostate cancer at biopsy--can we predict adverse pathological outcomes?

PubMed

Thong, Alan E; Shikanov, Sergey; Katz, Mark H; Gofrit, Ofer N; Eggener, Scott; Zagaja, Gregory P; Shalhav, Arieh L; Zorn, Kevin C

2008-12-01

Patients with Gleason score 6 microfocal prostate cancer, defined as 5% or less in 1 biopsy core, are often considered to have favorable disease. Few studies have addressed clinical parameters that predict pathological upgrading or up staging at radical prostatectomy. From a prospective database of 1,271 consecutive robot assisted laparoscopic prostatectomies performed from 2003 to 2008 patients with Gleason score 6 microfocal prostate cancer were identified. Adverse pathological outcome was defined as any upgrading and/or up staging on prostatectomy pathological findings. Multivariate logistic regression was used to evaluate the ability of patient age, clinical stage, the total number of biopsy cores, preoperative prostate specific antigen, prostate volume and pathological prostate specific antigen density to predict adverse pathological outcomes. A total of 192 patients with a median age of 59 years (range 42 to 73) were identified with Gleason score 6 prostate cancer involving 5% or less of 1 biopsy core, including 177 (92%) with clinical T1c disease. Mean +/- SD preoperative prostate specific antigen was 6.0 +/- 3.9 ng/ml (range 0.8 to 35). Overall 42 patients (22%) had adverse pathological outcomes, including upgrading in 35 (18%) and up staging in 16 (8%). Multivariate logistic regression revealed that age more than 65 years and pathological prostate specific antigen density greater than 0.20 ng/ml/gm were predictive of an increased risk of adverse pathological results (p = 0.0081 and 0.0169, respectively). While a microfocus of Gleason score 6 prostate cancer on biopsy is commonly considered low risk disease, there was a greater than 1/5 risk of pathological upgrading and/or up staging. Patients with Gleason score 6 microfocal prostate cancer should be counseled that they may harbor more aggressive disease, especially when pretreatment clinical risk factors are present, such as advanced age or high clinical prostate specific antigen density.

Multifunctional Envelope-Type siRNA Delivery Nanoparticle Platform for Prostate Cancer Therapy.

PubMed

Xu, Xiaoding; Wu, Jun; Liu, Yanlan; Saw, Phei Er; Tao, Wei; Yu, Mikyung; Zope, Harshal; Si, Michelle; Victorious, Amanda; Rasmussen, Jonathan; Ayyash, Dana; Farokhzad, Omid C; Shi, Jinjun

2017-03-28

With the capability of specific silencing of target gene expression, RNA interference (RNAi) technology is emerging as a promising therapeutic modality for the treatment of cancer and other diseases. One key challenge for the clinical applications of RNAi is the safe and effective delivery of RNAi agents such as small interfering RNA (siRNA) to a particular nonliver diseased tissue (e.g., tumor) and cell type with sufficient cytosolic transport. In this work, we proposed a multifunctional envelope-type nanoparticle (NP) platform for prostate cancer (PCa)-specific in vivo siRNA delivery. A library of oligoarginine-functionalized and sharp pH-responsive polymers was synthesized and used for self-assembly with siRNA into NPs with the features of long blood circulation and pH-triggered oligoarginine-mediated endosomal membrane penetration. By further modification with ACUPA, a small molecular ligand specifically recognizing prostate-specific membrane antigen (PSMA) receptor, this envelope-type nanoplatform with multifunctional properties can efficiently target PSMA-expressing PCa cells and silence target gene expression. Systemic delivery of the siRNA NPs can efficiently silence the expression of prohibitin 1 (PHB1), which is upregulated in PCa and other cancers, and significantly inhibit PCa tumor growth. These results suggest that this multifunctional envelope-type nanoplatform could become an effective tool for PCa-specific therapy.

Role of miR-452-5p in the tumorigenesis of prostate cancer: A study based on the Cancer Genome Atl(TCGA), Gene Expression Omnibus (GEO), and bioinformatics analysis.

PubMed

Gao, Li; Zhang, Li-Jie; Li, Sheng-Hua; Wei, Li-Li; Luo, Bin; He, Rong-Quan; Xia, Shuang

2018-03-06

MiR-452-5p has been reported to be down-regulated in prostate cancer, affecting the development of this type of cancer. However, the molecular mechanism of miR-452-5p in prostate cancer remains unclear. Therefore, we investigated the network of target genes of miR-452-5p in prostate cancer using bioinformatics analyses. We first analyzed the expression profiles and prognostic value of miR-452-5p in prostate cancer tissues from a public database. Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), PANTHER pathway analyses, and a disease ontology (DG) analysis were performed to find the molecular functions of the target genes from GSE datasets and miRWalk. Finally, we validated hub genes from the protein-protein interaction (PPI) networks of the target genes in the Human Protein Atlas (HPA) database and Gene Expression Profiling Interactive Analysis (GEPIA). Narrowing down the optimal target genes was conducted by seeking the common parts of up-regulated genes from GEPIA, down-regulated genes from GSE datasets, and predicted genes in miRWalk. Based on mining of GEO and ArrayExpress microarray chips and miRNA-Seq data in the TCGA database, which includes 1007 prostate cancer samples and 387 non-cancer samples, miR-452-5p is shown to be down-regulated in prostate cancer. GO, KEGG, and PANTHER pathway analyses suggested that the target genes might participate in important biological processes, such as transforming growth factor beta signaling and the positive regulation of brown fat cell differentiation and mesenchymal cell differentiation, as well as the Ras signaling pathway and pathways regulating the pluripotency of stem cells and arrhythmogenic right ventricular cardiomyopathy (ARVC). Nine genes-GABBR, PNISR, NTSR1, DOCK1, EREG, SFRP1, PTGS2, LEF1, and BMP2-were defined as hub genes in the PPI network. Three genes-FAM174B, SLC30A4, and SLIT1-were jointly shared by GEPIA, the GSE datasets, and miRWalk. Down-regulated miR-452-5p might play an essential role in the tumorigenesis of prostate cancer. Copyright © 2018. Published by Elsevier GmbH.

AEG-1 promoter-mediated imaging of prostate cancer

PubMed Central

Bhatnagar, Akrita; Wang, Yuchuan; Mease, Ronnie C.; Gabrielson, Matthew; Sysa, Polina; Minn, Il; Green, Gilbert; Simmons, Brian; Gabrielson, Kathleen; Sarkar, Siddik; Fisher, Paul B.; Pomper, Martin G.

2014-01-01

We describe a new imaging method for detecting prostate cancer, whether localized or disseminated and metastatic to soft tissues and bone. The method relies on the use of imaging reporter genes under the control of the promoter of AEG-1 (MTDH), which is selectively active only in malignant cells. Through systemic, nanoparticle-based delivery of the imaging construct, lesions can be identified through bioluminescence imaging and single photon emission-computed tomography in the PC3-ML murine model of prostate cancer at high sensitivity. This approach is applicable for the detection of prostate cancer metastases, including bone lesions for which there is no current reliable agent for non-invasive clinical imaging. Further, the approach compares favorably to accepted and emerging clinical standards, including positron emission tomography with [18F]fluorodeoxyglucose and [18F]sodium fluoride. Our results offer a preclinical proof of concept that rationalizes clinical evaluation in patients with advanced prostate cancer. PMID:25145668

Extra-prostatic Transgene-associated Neoplastic Lesions in Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) Mice

PubMed Central

Berman-Booty, Lisa D.; Thomas-Ahner, Jennifer M.; Bolon, Brad; Oglesbee, Michael J.; Clinton, Steven K.; Kulp, Samuel K.; Chen, Ching-Shih; La Perle, Krista

2014-01-01

Male transgenic adenocarcinoma of the mouse prostate (TRAMP) mice are frequently used in prostate cancer research because their prostates consistently develop a series of pre-neoplastic and neoplastic lesions. Disease progression in TRAMP mouse prostates culminates in metastatic, poorly differentiated carcinomas with neuroendocrine features. The androgen dependence of the rat probasin promoter largely limits transgene expression to the prostatic epithelium. However, extra-prostatic transgene-positive lesions have been described in TRAMP mice, including renal tubulo-acinar carcinomas, neuroendocrine carcinomas of the urethra, and phyllodes-like tumors of the seminal vesicle. Here we describe the histologic and immunohistochemical features of two novel extra-prostatic lesions in TRAMP mice: primary anaplastic tumors of uncertain cell origin in the midbrain, and poorly differentiated adenocarcinomas of the submandibular salivary gland. These newly characterized tumors apparently result from transgene expression in extra-prostatic locations rather than representing metastatic prostate neoplasms because lesions were identified in both male and female mice as well as in male TRAMP mice without histologically apparent prostate tumors. In this paper we also calculate the incidences of the urethral carcinomas and renal tubulo-acinar carcinomas, further elucidate the biological behavior of the urethral carcinomas, and demonstrate the critical importance of complete necropsies even when evaluating presumably well characterized phenotypes in genetically engineered mice. PMID:24742627

Extra-prostatic transgene-associated neoplastic lesions in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice.

PubMed

Berman-Booty, Lisa D; Thomas-Ahner, Jennifer M; Bolon, Brad; Oglesbee, Michael J; Clinton, Steven K; Kulp, Samuel K; Chen, Ching-Shih; La Perle, Krista M D

2015-02-01

Male transgenic adenocarcinoma of the mouse prostate (TRAMP) mice are frequently used in prostate cancer research because their prostates consistently develop a series of preneoplastic and neoplastic lesions. Disease progression in TRAMP mouse prostates culminates in metastatic, poorly differentiated carcinomas with neuroendocrine features. The androgen dependence of the rat probasin promoter largely limits transgene expression to the prostatic epithelium. However, extra-prostatic transgene-positive lesions have been described in TRAMP mice, including renal tubuloacinar carcinomas, neuroendocrine carcinomas of the urethra, and phyllodes-like tumors of the seminal vesicle. Here, we describe the histologic and immunohistochemical features of 2 novel extra-prostatic lesions in TRAMP mice: primary anaplastic tumors of uncertain cell origin in the midbrain and poorly differentiated adenocarcinomas of the submandibular salivary gland. These newly characterized tumors apparently result from transgene expression in extra-prostatic locations rather than representing metastatic prostate neoplasms because lesions were identified in both male and female mice and in male TRAMP mice without histologically apparent prostate tumors. In this article, we also calculate the incidences of the urethral carcinomas and renal tubuloacinar carcinomas, further elucidate the biological behavior of the urethral carcinomas, and demonstrate the critical importance of complete necropsies even when evaluating presumably well characterized phenotypes in genetically engineered mice. © 2014 by The Author(s).

TrueNTH sexual recovery study protocol: a multi-institutional collaborative approach to developing and testing a web-based intervention for couples coping with the side-effects of prostate cancer treatment in a randomized controlled trial.

PubMed

Wittmann, D; Mehta, A; Northouse, L; Dunn, R; Braun, T; Duby, A; An, L; Arab, L; Bangs, R; Bober, S; Brandon, J; Coward, M; Dunn, M; Galbraith, M; Garcia, M; Giblin, J; Glode, M; Koontz, B; Lowe, A; Mitchell, S; Mulhall, J; Nelson, C; Paich, K; Saigal, C; Skolarus, T; Stanford, J; Walsh, T; Pollack, C E

2017-10-02

Over half of men who receive treatment for prostate suffer from a range of sexual problems that affect negatively their sexual health, sexual intimacy with their partners and their quality of life. In clinical practice, however, care for the sexual side effects of treatment is often suboptimal or unavailable. The goal of the current study is to test a web-based intervention to support the recovery of sexual intimacy of prostate cancer survivors and their partners after treatment. The study team developed an interactive, web-based intervention, tailored to type of treatment received, relationship status (partnered/non-partnered) and sexual orientation. It consists of 10 modules, six follow the trajectory of the illness and four are theme based. They address sexual side effects, rehabilitation, psychological impacts and coaching for self-efficacy. Each includes a video to engage participants, psychoeducation and activities completed by participants on the web. Tailored strategies for identified concerns are sent by email after each module. Six of these modules will be tested in a randomized controlled trial and compared to usual care. Men with localized prostate cancer with partners will be recruited from five academic medical centers. These couples (N = 140) will be assessed prior to treatment, then 3 months and 6 months after treatment. The primary outcome will be the survivors' and partners' Global Satisfaction with Sex Life, assessed by a Patient Reported Outcome Measure Information Systems (PROMIS) measure. Secondary outcomes will include interest in sex, sexual activity, use of sexual aids, dyadic coping, knowledge about sexual recovery, grief about the loss of sexual function, and quality of life. The impact of the intervention on the couple will be assessed using the Actor-Partner Interaction Model, a mixed-effects linear regression model able to estimate both the association of partner characteristics with partner and patient outcomes and the association of patient characteristics with both outcomes. The web-based tool represents a novel approach to addressing the sexual health needs of prostate cancer survivors and their partners that-if found efficacious-will improve access to much needed specialty care in prostate cancer survivorship. Clinicaltrials.gov registration # NCT02702453 , registered on March 3, 2016.

Genetic Variations in SLCO Transporter Genes Contributing to Racial Disparity in Aggressiveness of Prostate Cancer

DTIC Science & Technology

2017-10-01

should not be construed as an official Department of the Army position, policy or decision unless so designated by other documentation. REPORT... control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE October 2017 2. REPORT TYPE Annual 3. DATES COVERED 15 Sep 2016...statistically significant difference among these three groups in either tumor characteristics including Gleason score, stage and aggressiveness, or

Regulation of Prostate Cancer Bone Metastasis by DKK1

DTIC Science & Technology

2012-09-01

information is estimated to average 1 hour per response , including the time for reviewing instructions, searching existing data sources, gathering and...ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON USAMRMC a. REPORT U b. ABSTRACT U c. THIS PAGE U UU 13 19b. TELEPHONE NUMBER...cells into bone irrevocably alters the bone microenvironment and initiates a skeletal response that is dependent on the type of tumor (1). Breast

Detecting prostate cancer and prostatic calcifications using advanced magnetic resonance imaging

PubMed Central

Dou, Shewei; Bai, Yan; Shandil, Ankit; Ding, Degang; Shi, Dapeng; Haacke, E Mark; Wang, Meiyun

2017-01-01

Prostate cancer and prostatic calcifications have a high incidence in elderly men. We aimed to investigate the diagnostic capabilities of susceptibility-weighted imaging in detecting prostate cancer and prostatic calcifications. A total number of 156 men, including 34 with prostate cancer and 122 with benign prostate were enrolled in this study. Computed tomography, conventional magnetic resonance imaging, diffusion-weighted imaging, and susceptibility-weighted imaging were performed on all the patients. One hundred and twelve prostatic calcifications were detected in 87 patients. The sensitivities and specificities of the conventional magnetic resonance imaging, apparent diffusion coefficient, and susceptibility-filtered phase images in detecting prostate cancer and prostatic calcifications were calculated. McNemar's Chi-square test was used to compare the differences in sensitivities and specificities between the techniques. The results showed that the sensitivity and specificity of susceptibility-filtered phase images in detecting prostatic cancer were greater than that of conventional magnetic resonance imaging and apparent diffusion coefficient (P < 0.05). In addition, the sensitivity and specificity of susceptibility-filtered phase images in detecting prostatic calcifications were comparable to that of computed tomography and greater than that of conventional magnetic resonance imaging and apparent diffusion coefficient (P < 0.05). Given the high incidence of susceptibility-weighted imaging (SWI) abnormality in prostate cancer, we conclude that susceptibility-weighted imaging is more sensitive and specific than conventional magnetic resonance imaging, diffusion-weighted imaging, and computed tomography in detecting prostate cancer. Furthermore, susceptibility-weighted imaging can identify prostatic calcifications similar to computed tomography, and it is much better than conventional magnetic resonance imaging and diffusion-weighted imaging. PMID:27004542

Detecting prostate cancer and prostatic calcifications using advanced magnetic resonance imaging.

PubMed

Dou, Shewei; Bai, Yan; Shandil, Ankit; Ding, Degang; Shi, Dapeng; Haacke, E Mark; Wang, Meiyun

2017-01-01

Prostate cancer and prostatic calcifications have a high incidence in elderly men. We aimed to investigate the diagnostic capabilities of susceptibility-weighted imaging in detecting prostate cancer and prostatic calcifications. A total number of 156 men, including 34 with prostate cancer and 122 with benign prostate were enrolled in this study. Computed tomography, conventional magnetic resonance imaging, diffusion-weighted imaging, and susceptibility-weighted imaging were performed on all the patients. One hundred and twelve prostatic calcifications were detected in 87 patients. The sensitivities and specificities of the conventional magnetic resonance imaging, apparent diffusion coefficient, and susceptibility-filtered phase images in detecting prostate cancer and prostatic calcifications were calculated. McNemar's Chi-square test was used to compare the differences in sensitivities and specificities between the techniques. The results showed that the sensitivity and specificity of susceptibility-filtered phase images in detecting prostatic cancer were greater than that of conventional magnetic resonance imaging and apparent diffusion coefficient (P < 0.05). In addition, the sensitivity and specificity of susceptibility-filtered phase images in detecting prostatic calcifications were comparable to that of computed tomography and greater than that of conventional magnetic resonance imaging and apparent diffusion coefficient (P < 0.05). Given the high incidence of susceptibility-weighted imaging (SWI) abnormality in prostate cancer, we conclude that susceptibility-weighted imaging is more sensitive and specific than conventional magnetic resonance imaging, diffusion-weighted imaging, and computed tomography in detecting prostate cancer. Furthermore, susceptibility-weighted imaging can identify prostatic calcifications similar to computed tomography, and it is much better than conventional magnetic resonance imaging and diffusion-weighted imaging.

Co regulation of srGAP1 by Wnt and androgen receptor signaling: a new target for treatment of CRPC

DTIC Science & Technology

2016-12-01

with this disease are asymptomatic [1, 2]. Most of these asymptomatic cases are prostate can- cers which may be managed by watchful wait- ing and...nohistochemistry staining in 212 prostate can- cer specimens, including 122 localized pros- tate cancer from prostectomy specimens and 90 from CRPC...at rapid autopsy (including three dif- ferent foci from the same patient) and 11 treat- ment-naïve, high-grade localized prostate can- cers . They also

Matrix-Dependent Regulation of AKT in Hepsin-Overexpressing PC3 Prostate Cancer Cells12

PubMed Central

Wittig-Blaich, Stephanie M; Kacprzyk, Lukasz A; Eismann, Thorsten; Bewerunge-Hudler, Melanie; Kruse, Petra; Winkler, Eva; Strauss, Wolfgang S L; Hibst, Raimund; Steiner, Rudolf; Schrader, Mark; Mertens, Daniel; Sültmann, Holger; Wittig, Rainer

2011-01-01

The serine-protease hepsin is one of the most prominently overexpressed genes in human prostate carcinoma. Forced expression of the enzyme in mice prostates is associated with matrix degradation, invasive growth, and prostate cancer progression. Conversely, hepsin overexpression in metastatic prostate cancer cell lines was reported to induce cell cycle arrest and reduction of invasive growth in vitro. We used a system for doxycycline (dox)-inducible target gene expression in metastasis-derived PC3 cells to analyze the effects of hepsin in a quantitative manner. Loss of viability and adhesion correlated with hepsin expression levels during anchorage-dependent but not anchorage-independent growth. Full expression of hepsin led to cell death and detachment and was specifically associated with reduced phosphorylation of AKT at Ser473, which was restored by growth on matrix derived from RWPE1 normal prostatic epithelial cells. In the chorioallantoic membrane xenograft model, hepsin overexpression in PC3 cells reduced the viability of tumors but did not suppress invasive growth. The data presented here provide evidence that elevated levels of hepsin interfere with cell adhesion and viability in the background of prostate cancer as well as other tissue types, the details of which depend on the microenvironment provided. Our findings suggest that overexpression of the enzyme in prostate carcinogenesis must be spatially and temporally restricted for the efficient development of tumors and metastases. PMID:21750652

Urine Flow Dynamics Through Prostatic Urethra With Tubular Organ Modeling Using Endoscopic Imagery

PubMed Central

Kambara, Yoichi; Yamanishi, Tomonori; Naya, Yukio; Igarashi, Tatsuo

2014-01-01

Voiding dysfunction is common in the aged male population. However, the obstruction mechanism in the lower urinary tract and critical points for obstruction remains uncertain. The aim of this paper was to develop a system to investigate the relationship between voiding dysfunction and alteration of the shape of the prostatic urethra by processing endoscopic video images of the urethra and analyzing the fluid dynamics of the urine stream. A panoramic image of the prostatic urethra was generated from cystourethroscopic video images. A virtual 3-D model of the urethra was constructed using the luminance values in the image. Fluid dynamics using the constructed model was then calculated assuming a static urethra and maximum urine flow rate. Cystourethroscopic videos from 11 patients with benign prostatic hyperplasia were recorded around administration of an alpha-1 adrenoceptor antagonist. The calculated pressure loss through the prostatic urethra in each model corresponded to the prostatic volume, and the improvements of the pressure loss after treatment correlated to the conventional clinical indices. As shown by the proposed method, the shape of the prostatic urethra affects the transporting urine fluid energy, and this paper implies a possible method for detecting critical lesions responsible for voiding dysfunction. The proposed method provides critical information about deformation of the prostatic urethra on voiding function. Detailed differences in the various types of relaxants for the lower urinary tract could be estimated. PMID:27170869

Influence of the neural microenvironment on prostate cancer.

PubMed

Coarfa, Christian; Florentin, Diego; Putluri, NagiReddy; Ding, Yi; Au, Jason; He, Dandan; Ragheb, Ahmed; Frolov, Anna; Michailidis, George; Lee, MinJae; Kadmon, Dov; Miles, Brian; Smith, Christopher; Ittmann, Michael; Rowley, David; Sreekumar, Arun; Creighton, Chad J; Ayala, Gustavo

2018-02-01

Nerves are key factors in prostate cancer (PCa), but the functional role of innervation in prostate cancer is poorly understood. PCa induced neurogenesis and perineural invasion (PNI), are associated with aggressive disease. We denervated rodent prostates chemically and physically, before orthotopically implanting cancer cells. We also performed a human neoadjuvant clinical trial using botulinum toxin type A (Botox) and saline in the same patient, before prostatectomy. Bilateral denervation resulted in reduced tumor incidence and size in mice. Botox treatment in humans resulted in increased apoptosis of cancer cells in the Botox treated side. A similar denervation gene array profile was identified in tumors arising in denervated rodent prostates, in spinal cord injury patients and in the Botox treated side of patients. Denervation induced exhibited a signature gene profile, indicating translation and bioenergetic shutdown. Nerves also regulate basic cellular functions of non-neoplastic epithelial cells. Nerves play a role in the homeostasis of normal epithelial tissues and are involved in prostate cancer tumor survival. This study confirms that interactions between human cancer and nerves are essential to disease progression. This work may make a major impact in general cancer treatment strategies, as nerve/cancer interactions are likely important in other cancers as well. Targeting the neural microenvironment may represent a therapeutic approach for the treatment of human prostate cancer. © 2017 The Authors. The Prostate Published by Wiley Periodicals, Inc.

Egr1 Target Genes That Regulate Growth/Survival of Prostate Cells

DTIC Science & Technology

2005-03-01

led to the followed by immunoprecipitation with antibodies to Egrl following study that defined the role of Egrl in prostate (ChIP). To detect...with UV-C (40 J/Mr) were chromatin crosslinked and then immuntoprecipitated with a specific Egri antibody (rE) or a nonimmune control IgG antibody [aN...86 A 󈧬 Mi2 B him . Figure 2. C8P/p300 Are Upregulated by Egrl 120 serum 0 1 2 3 0 1 in Serum-Induced Prostate Cells and in Wild- 10o -4-.cRP PM Type

Sarcosine influences apoptosis and growth of prostate cells via cell-type specific regulation of distinct sets of genes.

PubMed

Rodrigo, Miguel A Merlos; Strmiska, Vladislav; Horackova, Eva; Buchtelova, Hana; Michalek, Petr; Stiborova, Marie; Eckschlager, Tomas; Adam, Vojtech; Heger, Zbynek

2018-02-01

Sarcosine is a widely discussed oncometabolite of prostate cells. Although several reports described connections between sarcosine and various phenotypic changes of prostate cancer (PCa) cells, there is still a lack of insights on the complex phenomena of its effects on gene expression patterns, particularly in non-malignant and non-metastatic cells. To shed more light on this phenomenon, we performed parallel microarray profiling of RNA isolated from non-malignant (PNT1A), malignant (22Rv1), and metastatic (PC-3) prostate cell lines treated with sarcosine. Microarray results were experimentally verified using semi-quantitative-RT-PCR, clonogenic assay, through testing of the susceptibility of cells pre-incubated with sarcosine to anticancer agents with different modes of actions (inhibitors of topoisomerase II, DNA cross-linking agent, antimicrotubule agent and inhibitor of histone deacetylases) and by evaluation of activation of executioner caspases 3/7. We identified that irrespective of the cell type, sarcosine stimulates up-regulation of distinct sets of genes involved in cell cycle and mitosis, while down-regulates expression of genes driving apoptosis. Moreover, it was found that in all cell types, sarcosine had pronounced stimulatory effects on clonogenicity. Except of an inhibitor of histone deacetylase valproic acid, efficiency of all agents was significantly (P < 0.05) decreased in sarcosine pre-incubated cells. Our comparative study brings evidence that sarcosine affects not only metastatic PCa cells, but also their malignant and non-malignant counterparts and induces very similar changes in cells behavior, but via distinct cell-type specific targets. © 2017 Wiley Periodicals, Inc.

WE-DE-201-12: Thermal and Dosimetric Properties of a Ferrite-Based Thermo-Brachytherapy Seed

DOE Office of Scientific and Technical Information (OSTI.GOV)

Warrell, G; Shvydka, D; Parsai, E I

Purpose: The novel thermo-brachytherapy (TB) seed provides a simple means of adding hyperthermia to LDR prostate permanent implant brachytherapy. The high blood perfusion rate (BPR) within the prostate motivates the use of the ferrite and conductive outer layer design for the seed cores. We describe the results of computational analyses of the thermal properties of this ferrite-based TB seed in modelled patient-specific anatomy, as well as studies of the interseed and scatter (ISA) effect. Methods: The anatomies (including the thermophysical properties of the main tissue types) and seed distributions of 6 prostate patients who had been treated with LDR brachytherapymore » seeds were modelled in the finite element analysis software COMSOL, using ferrite-based TB and additional hyperthermia-only (HT-only) seeds. The resulting temperature distributions were compared to those computed for patient-specific seed distributions, but in uniform anatomy with a constant blood perfusion rate. The ISA effect was quantified in the Monte Carlo software package MCNP5. Results: Compared with temperature distributions calculated in modelled uniform tissue, temperature distributions in the patient-specific anatomy were higher and more heterogeneous. Moreover, the maximum temperature to the rectal wall was typically ∼1 °C greater for patient-specific anatomy than for uniform anatomy. The ISA effect of the TB and HT-only seeds caused a reduction in D90 similar to that found for previously-investigated NiCu-based seeds, but of a slightly smaller magnitude. Conclusion: The differences between temperature distributions computed for uniform and patient-specific anatomy for ferrite-based seeds are significant enough that heterogeneous anatomy should be considered. Both types of modelling indicate that ferrite-based seeds provide sufficiently high and uniform hyperthermia to the prostate, without excessively heating surrounding tissues. The ISA effect of these seeds is slightly less than that for the previously-presented NiCu-based seeds.« less

Cost-effectiveness of denosumab versus zoledronic acid for preventing skeletal-related events in the Czech Republic.

PubMed

Cristino, Joaquim; Finek, Jíndřich; Jandova, Petra; Kolek, Martin; Pásztor, Bálint; Giannopoulou, Christina; Qian, Yi; Brezina, Tomas; Lothgren, Mickael

2017-08-01

This study assessed the cost-effectiveness of the subcutaneous RANKL inhibitor, denosumab, vs the intravenous bisphosphonate, zoledronic acid, for the prevention of skeletal-related events (SREs) in patients with prostate cancer, breast cancer, and other solid tumors (OST) in the Czech Republic. A lifetime Markov model was developed to compare the effects of denosumab and zoledronic acid on costs (including drug costs and administration, patient management, SREs, and adverse events), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios from a national payer perspective. Different discount rates, time horizons, SRE rates, distributions, and nature (asymptomatic vs all SREs), and the inclusion of treatment discontinuation were considered in scenario analyses. The robustness of the model was tested using deterministic and probabilistic sensitivity analyses. Across tumor types, denosumab was associated with fewer SREs, improved QALYs, and higher total costs over a lifetime. The incremental cost per QALY gained for denosumab vs zoledronic acid was 382,673 CZK for prostate cancer, 408,450 CZK for breast cancer, and 608,133 CZK for OST. Incremental costs per SRE avoided for the same tumor type were 54,007 CZK, 51,765 CZK, and 94,426 CZK, respectively. In scenario analyses, the results remained similar to baseline, when different discount rates and time horizons were considered. At a non-official willingness-to-pay threshold of 1.2 million CZK, the probabilities of denosumab being cost-effective vs zoledronic acid were 0.64, 0.67, and 0.49 for prostate cancer, breast cancer, and OST, respectively. The SRE rates used were obtained from clinical trials; studies suggest rates may be higher in clinical practice. Additional evidence on real-world SRE rates could further improve the accuracy of the modeling. Compared with zoledronic acid, denosumab provides a cost-effective treatment option for the prevention of SREs in patients with prostate cancer, breast cancer, and OST in the Czech Republic.

Detection of prostate cancer index lesions with multiparametric magnetic resonance imaging (mp-MRI) using whole-mount histological sections as the reference standard.

PubMed

Russo, Filippo; Regge, Daniele; Armando, Enrico; Giannini, Valentina; Vignati, Anna; Mazzetti, Simone; Manfredi, Matteo; Bollito, Enrico; Correale, Loredana; Porpiglia, Francesco

2016-07-01

To evaluate the sensitivity of multiparametric magnetic resonance imaging (mp-MRI) for detecting prostate cancer foci, including the largest (index) lesions. In all, 115 patients with biopsy confirmed prostate cancer underwent mp-MRI before radical prostatectomy. A single expert radiologist recorded all prostate cancer foci including the index lesion 'blinded' to the pathologist's biopsy report. Stained whole-mount histological sections were used as the reference standard. All lesions were contoured by an experienced uropathologist who assessed their volume and pathological Gleason score. All lesions with a volume of >0.5 mL and/or pathological Gleason score of >6 were defined as clinically significant prostate cancer. Multivariate analysis was used to ascertain the characteristics of lesions identified by MRI. In all, 104 of 115 index lesions were correctly diagnosed by mp-MRI (sensitivity 90.4%; 95% confidence interval [CI] 83.5-95.1%), including 98/105 clinically significant index lesions (93.3%; 95% CI 86.8-97.3%), among which three of three lesions had a volume of <0.5 mL and Gleason score of >6. Overall, mp-MRI detected 131/206 lesions including 13 of 68 'insignificant' prostate cancers. The multivariate logistic regression modelling showed that pathological Gleason score (odds ratio [OR] 11.7, 95% CI 2.3-59.8; P = 0.003) and lesion volume (OR 4.24, 95% CI 1.3-14.7; P = 0.022) were independently associated with the detection of index lesions at MRI. This study shows that mp-MRI has a high sensitivity for detecting clinically significant prostate cancer index lesions, while having disappointing results for the detection of small-volume, low Gleason score prostate cancer foci. Thus, mp-MRI could be used to stratify patients according to risk, allowing better treatment selection. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.

Prostate-Specific Natural Health Products (Dietary Supplements) Radiosensitize Normal Prostate Cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hasan, Yasmin; Schoenherr, Diane; Martinez, Alvaro A.

Purpose: Prostate-specific health products (dietary supplements) are taken by cancer patients to alleviate the symptoms linked with poor prostate health. However, the effect of these agents on evidence-based radiotherapy practice is poorly understood. The present study aimed to determine whether dietary supplements radiosensitized normal prostate or prostate cancer cell lines. Methods and Materials: Three well-known prostate-specific dietary supplements were purchased from commercial sources available to patients (Trinovin, Provelex, and Prostate Rx). The cells used in the study included normal prostate lines (RWPE-1 and PWR-1E), prostate tumor lines (PC3, DU145, and LNCaP), and a normal nonprostate line (HaCaT). Supplement toxicity wasmore » assessed using cell proliferation assays [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] and cellular radiosensitivity using conventional clonogenic assays (0.5-4Gy). Cell cycle kinetics were assessed using the bromodeoxyuridine/propidium iodide pulse-labeling technique, apoptosis by scoring caspase-3 activation, and DNA repair by assessing gammaH2AX. Results: The cell growth and radiosensitivity of the malignant PC3, DU145, and LNcaP cells were not affected by any of the dietary prostate supplements (Provelex [2mug/mL], Trinovin [10mug/mL], and Prostate Rx [50 mug/mL]). However, both Trinovin (10mug/mL) and Prostate Rx (6mug/mL) inhibited the growth rate of the normal prostate cell lines. Prostate Rx increased cellular radiosensitivity of RWPE-1 cells through the inhibition of DNA repair. Conclusion: The use of prostate-specific dietary supplements should be discouraged during radiotherapy owing to the preferential radiosensitization of normal prostate cells.« less

Are prostatic calculi independent predictive factors of lower urinary tract symptoms?

PubMed Central

Park, Sung-Woo; Nam, Jong-Kil; Lee, Sang-Don; Chung, Moon-Kee

2010-01-01

We determined the correlation between prostatic calculi and lower urinary tract symptoms (LUTS), as well as the predisposing factors of prostatic calculi. Of the 1 527 patients who presented at our clinic for LUTS, 802 underwent complete evaluations, including transrectal ultrasonography, voided bladder-3 specimen and international prostatic symptoms score (IPSS). A total of 335 patients with prostatic calculi and 467 patients without prostatic calculi were divided into calculi and no calculi groups, respectively. Predictive factors of severe LUTS and prostatic calculi were determined using uni/multivariate analysis. The overall IPSS score was 15.7 ± 9.2 and 14.1 ± 9.2 in the calculi and no calculi group, respectively (P = 0.013). The maximum flow rate was 12.1 ± 6.9 and 14.2 ± 8.2 mL s−1 in the calculi and no calculi group, respectively (P = 0.003). On univariate analysis for predicting factors of severe LUTS, differences on age (P = 0.042), prostatic calculi (P = 0.048) and prostatitis (P = 0.018) were statistically significant. However, on multivariate analysis, no factor was significant. On multivariate analysis for predisposing factors of prostatic calculi, differences on age (P < 0.001) and prostate volume (P = 0.001) were significant. To our knowledge, patients who have prostatic calculi complain of more severe LUTS. However, prostatic calculi are not an independent predictive factor of severe LUTS. Therefore, men with prostatic calculi have more severe LUTS not only because of prostatic calculi but also because of age and other factors. In addition, old age and large prostate volume are independent predisposing factors for prostatic calculi. PMID:19966831

A human prostatic bacterial isolate alters the prostatic microenvironment and accelerates prostate cancer progression.

PubMed

Simons, Brian W; Durham, Nicholas M; Bruno, Tullia C; Grosso, Joseph F; Schaeffer, Anthony J; Ross, Ashley E; Hurley, Paula J; Berman, David M; Drake, Charles G; Thumbikat, Praveen; Schaeffer, Edward M

2015-02-01

Inflammation is associated with several diseases of the prostate including benign enlargement and cancer, but a causal relationship has not been established. Our objective was to characterize the prostate inflammatory microenvironment after infection with a human prostate-derived bacterial strain and to determine the effect of inflammation on prostate cancer progression. To this end, we mimicked typical human prostate infection with retrograde urethral instillation of CP1, a human prostatic isolate of Escherichia coli. CP1 bacteria were tropic for the accessory sex glands and induced acute inflammation in the prostate and seminal vesicles, with chronic inflammation lasting at least 1 year. Compared to controls, infection induced both acute and chronic inflammation with epithelial hyperplasia, stromal hyperplasia, and inflammatory cell infiltrates. In areas of inflammation, epithelial proliferation and hyperplasia often persist, despite decreased expression of androgen receptor (AR). Inflammatory cells in the prostates of CP1-infected mice were characterized at 8 weeks post-infection by flow cytometry, which showed an increase in macrophages and lymphocytes, particularly Th17 cells. Inflammation was additionally assessed in the context of carcinogenesis. Multiplex cytokine profiles of inflamed prostates showed that distinct inflammatory cytokines were expressed during prostate inflammation and cancer, with a subset of cytokines synergistically increased during concurrent inflammation and cancer. Furthermore, CP1 infection in the Hi-Myc mouse model of prostate cancer accelerated the development of invasive prostate adenocarcinoma, with 70% more mice developing cancer by 4.5 months of age. This study provides direct evidence that prostate inflammation accelerates prostate cancer progression and gives insight into the microenvironment changes induced by inflammation that may accelerate tumour initiation or progression. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Dietary phenethyl isothiocyanate inhibition of androgen-responsive LNCaP prostate cancer cell tumor growth correlates with decreased angiogenesis

USDA-ARS?s Scientific Manuscript database

Phenethyl isothiocyanate (PEITC), found in certain cruciferous vegetables, has antitumor activity in several cancer models, including prostate cancer. In our xenograft model, dietary administration of PEITC (100-150 mg/kg/d) inhibited androgen-responsive LNCaP human prostate cancer cell tumor growth...

Quality of radiotherapy reporting in randomized controlled trials of prostate cancer.

PubMed

Soon, Yu Yang; Chen, Desiree; Tan, Teng Hwee; Tey, Jeremy

2018-06-07

Good radiotherapy reporting in clinical trials of prostate radiotherapy is important because it will allow accurate reproducibility of radiotherapy treatment and minimize treatment variations that can affect patient outcomes. The aim of our study is to assess the quality of prostate radiotherapy (RT) treatment reporting in randomized controlled trials in prostate cancer. We searched MEDLINE for randomized trials of prostate cancer, published from 1996 to 2016 and included prostate RT as one of the intervention arms. We assessed if the investigators reported the ten criteria adequately in the trial reports: RT dose prescription method; RT dose-planning procedures; organs at risk (OAR) dose constraints; target volume definition, simulation procedures; treatment verification procedures; total RT dose; fractionation schedule; conduct of quality assurance (QA) as well as presence or absence of deviations in RT treatment planning and delivery. We performed multivariate logistic regression to determine the factors that may influence the quality of reporting. We found 59 eligible trials. There was significant variability in the quality of reporting. Target volume definition, total RT dose and fractionation schedule were reported adequately in 97% of included trials. OAR constraints, simulation procedures and presence or absence of deviations in RT treatment planning and delivery were reported adequately in 30% of included trials. Twenty-four trials (40%) reported seven criteria or more adequately. Multivariable logistic analysis showed that trials that published their quality assurance results and cooperative group trials were more likely to have adequate quality in reporting in at least seven criteria. There is significant variability in the quality of reporting on prostate radiotherapy treatment in randomized trials of prostate cancer. We need to have consensus guidelines to standardize the reporting of radiotherapy treatment in randomized trials.

Prostate Artery Embolization as a New Treatment for Benign Prostate Hyperplasia: Contemporary Status in 2016.

PubMed

Noor, Amir; Fischman, Aaron M

2016-07-01

The gold standard treatment for benign prostate hyperplasia (BPH) is transurethral resection of the prostate (TURP) or open prostatectomy (OP). Recently, there has been increased interest and research in less invasive alternative treatments with less morbidity including prostate artery embolization (PAE). Several studies have shown PAE to be an effective alternative to TURP to treat lower urinary tract symptoms (LUTS) associated with BPH with decreased morbidity. Specifically, PAE has been advantageous in selected patient populations such as those with prostates too large for TURP or unsuitable surgical candidates, showing a promising potential for the future care of patients with BPH. Further studies are being done to demonstrate the clinical applications and advantages of this therapy in reduction of LUTS.

Protocols for Migration and Invasion Studies in Prostate Cancer.

PubMed

van de Merbel, Arjanneke F; van der Horst, Geertje; Buijs, Jeroen T; van der Pluijm, Gabri

2018-01-01

Prostate cancer is the most common malignancy diagnosed in men in the western world. The development of distant metastases and therapy resistance are major clinical problems in the management of prostate cancer patients. In order for prostate cancer to metastasize to distant sites in the human body, prostate cancer cells have to migrate and invade neighboring tissue. Cancer cells can acquire a migratory and invasive phenotype in several ways, including single cell and collective migration. As a requisite for migration, epithelial prostate cancer cells often need to acquire a motile, mesenchymal-like phenotype. This way prostate cancer cells often lose polarity and epithelial characteristics (e.g., expression of E-cadherin homotypic adhesion receptor), and acquire mesenchymal phenotype (for example, cytoskeletal rearrangements, enhanced expression of proteolytic enzymes and other repertory of integrins). This process is referred to as epithelial-to-mesenchymal transition (EMT). Cellular invasion, one of the hallmarks of cancer, is characterized by the movement of cells through a three-dimensional matrix, resulting in remodeling of the cellular environment. Cellular invasion requires adhesion, proteolysis of the extracellular matrix, and migration of cells. Studying the migratory and invasive ability of cells in vitro represents a useful tool to assess the aggressiveness of solid cancers, including those of the prostate.This chapter provides a comprehensive description of the Transwell migration assay, a commonly used technique to investigate the migratory behavior of prostate cancer cells in vitro. Furthermore, we will provide an overview of the adaptations to the Transwell migration protocol to study the invasive capacity of prostate cancer cells, i.e., the Transwell invasion assay. Finally, we will present a detailed description of the procedures required to stain the Transwell filter inserts and quantify the migration and/or invasion.

Multi-drug loaded micelles delivering chemotherapy and targeted therapies directed against HSP90 and the PI3K/AKT/mTOR pathway in prostate cancer.

PubMed

Le, Bao; Powers, Ginny L; Tam, Yu Tong; Schumacher, Nicholas; Malinowski, Rita L; Steinke, Laura; Kwon, Glen; Marker, Paul C

2017-01-01

Advanced prostate cancers that are resistant to all current therapies create a need for new therapeutic strategies. One recent innovative approach to cancer therapy is the simultaneous use of multiple FDA-approved drugs to target multiple pathways. A challenge for this approach is caused by the different solubility requirements of each individual drug, resulting in the need for a drug vehicle that is non-toxic and capable of carrying multiple water-insoluble antitumor drugs. Micelles have recently been shown to be new candidate drug solubilizers for anti cancer therapy. This study set out to examine the potential use of multi-drug loaded micelles for prostate cancer treatment in preclinical models including cell line and mouse models for prostate cancers with Pten deletions. Specifically antimitotic agent docetaxel, mTOR inhibitor rapamycin, and HSP90 inhibitor 17-N-allylamino-17-demethoxygeldanamycin were incorporated into the micelle system (DR17) and tested for antitumor efficacy. In vitro growth inhibition of prostate cancer cells was greater when all three drugs were used in combination compared to each individual drug, and packaging the drugs into micelles enhanced the cytotoxic effects. At the molecular level DR17 targeted simultaneously several molecular signaling axes important in prostate cancer including androgen receptor, mTOR, and PI3K/AKT. In a mouse genetic model of prostate cancer, DR17 treatment decreased prostate weight, which was achieved by both increasing caspase-dependent cell death and decreasing cell proliferation. Similar effects were also observed when DR17 was administered to nude mice bearing prostate cancer cells xenografts. These results suggest that combining these three cancer drugs in multi-drug loaded micelles may be a promising strategy for prostate cancer therapy.

Evaluation of Prostate Cancer with Radiolabeled Amino Acid Analogs.

PubMed

Schuster, David M; Nanni, Cristina; Fanti, Stefano

2016-10-01

Conventional imaging of prostate cancer has limitations related to the frequently indolent biology of the disease. PET is a functional imaging method that can exploit various aspects of tumor biology to enable greater detection of prostate cancer than can be provided by morphologic imaging alone. Radiotracers that are in use or under investigation for targeting salient features of prostate cancer include those directed to glucose, choline, acetate, prostate-specific membrane antigen, bombesin, and amino acids. The tumor imaging features of this last class of radiotracers mirror the upregulation of transmembrane amino acid transport that is necessary in carcinomas because of increased amino acid use for energy requirements and protein synthesis. Natural and synthetic amino acids radiolabeled for PET imaging have been investigated in prostate cancer patients. Early work with naturally occurring amino acid-derived radiotracers, such as l- 11 C-methionine and l-1- 11 C-5-hydroxytryptophan, demonstrated promising results, including greater sensitivity than 18 F-FDG for intraprostatic and extraprostatic cancer detection. However, limitations with naturally occurring amino acid-derived compounds, including metabolism of the radiotracer itself, led to the development of synthetic amino acid radiotracers, which are not metabolized and therefore more accurately reflect transmembrane amino acid transport. Of the synthetic amino acid-derived PET radiotracers, anti-1-amino-3- 18 F-fluorocyclobutane-1-carboxylic acid ( 18 F-FACBC or 18 F-fluciclovine) has undergone the most promising translation to human use, including the availability of simplified radiosynthesis. Several studies have indicated advantageous biodistribution in the abdomen and pelvis with little renal excretion and bladder activity-characteristics beneficial for prostate cancer imaging. Studies have demonstrated improved lesion detection and diagnostic performance of 18 F-fluciclovine in comparison with conventional imaging, especially for recurrent prostate cancer, although issues with nonspecific uptake limit the potential role of 18 F-fluciclovine in the diagnosis of primary prostate cancer. Although work is ongoing, recently published intrapatient comparisons of 18 F-fluciclovine with 11 C-choline reported higher overall diagnostic performance of the former, especially for the detection of disease relapse. This review is aimed at providing a detailed overview of amino acid-derived PET compounds that have been studied for use in prostate cancer imaging. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Survival Outcomes of Whole-Pelvic Versus Prostate-Only Radiation Therapy for High-Risk Prostate Cancer Patients With Use of the National Cancer Data Base

DOE Office of Scientific and Technical Information (OSTI.GOV)

Amini, Arya; Jones, Bernard L.; Yeh, Norman

Purpose/Objectives: The addition of whole pelvic (WP) compared with prostate-only (PO) radiation therapy (RT) for clinically node-negative prostate cancer remains controversial. The purpose of our study was to evaluate the survival benefit of adding WPRT versus PO-RT for high-risk, node-negative prostate cancer, using the National Cancer Data Base (NCDB). Methods and Materials: Patients with high-risk prostate cancer treated from 2004 to 2006, with available data for RT volume, coded as prostate and pelvis (WPRT) or prostate alone (PO-RT) were included. Multivariate analysis (MVA) and propensity-score matched analysis (PSM) were performed. Recursive partitioning analysis (RPA) based on overall survival (OS) usingmore » Gleason score (GS), T stage, and pretreatment prostate-specific antigen (PSA) was also conducted. Results: A total of 14,817 patients were included: 7606 (51.3%) received WPRT, and 7211 (48.7%) received PO-RT. The median follow-up time was 81 months (range, 2-122 months). Under MVA, the addition of WPRT for high-risk patients had no OS benefit compared with PO-RT (HR 1.05; P=.100). On subset analysis, patients receiving dose-escalated RT also did not benefit from WPRT (HR 1.01; P=.908). PSM confirmed no survival benefit with the addition of WPRT for high-risk patients (HR 1.05; P=.141). In addition, RPA was unable to demonstrate a survival benefit of WPRT for any subset. Other prognostic factors for inferior OS under MVA included older age (HR 1.25; P<.001), increasing comorbidity scores (HR 1.46; P<.001), higher T stage (HR 1.17; P<.001), PSA (HR 1.81; P<.001), and GS (HR 1.29; P<.001), and decreasing median county household income (HR 1.15; P=.011). Factors improving OS included the addition of androgen deprivation therapy (HR 0.92; P=.033), combination external beam RT plus brachytherapy boost (HR 0.71; P<.001), and treatment at an academic/research institution (HR 0.84; P=.002). Conclusion: In the largest reported analysis of WPRT for patients with high-risk prostate cancer treated in the dose-escalated era, the addition of WPRT demonstrated no survival advantage compared with PO-RT.« less

Prostate specific antigen density to predict prostate cancer upgrading in a contemporary radical prostatectomy series: a single center experience.

PubMed

Magheli, Ahmed; Hinz, Stefan; Hege, Claudia; Stephan, Carsten; Jung, Klaus; Miller, Kurt; Lein, Michael

2010-01-01

We investigated the value of pretreatment prostate specific antigen density to predict Gleason score upgrading in light of significant changes in grading routine in the last 2 decades. Of 1,061 consecutive men who underwent radical prostatectomy between 1999 and 2004, 843 were eligible for study. Prostate specific antigen density was calculated and a cutoff for highest accuracy to predict Gleason upgrading was determined using ROC curve analysis. The predictive accuracy of prostate specific antigen and prostate specific antigen density to predict Gleason upgrading was evaluated using ROC curve analysis based on predicted probabilities from logistic regression models. Prostate specific antigen and prostate specific antigen density predicted Gleason upgrading on univariate analysis (as continuous variables OR 1.07 and 7.21, each p <0.001) and on multivariate analysis (as continuous variables with prostate specific antigen density adjusted for prostate specific antigen OR 1.07, p <0.001 and OR 4.89, p = 0.037, respectively). When prostate specific antigen density was added to the model including prostate specific antigen and other Gleason upgrading predictors, prostate specific antigen lost its predictive value (OR 1.02, p = 0.423), while prostate specific antigen density remained an independent predictor (OR 4.89, p = 0.037). Prostate specific antigen density was more accurate than prostate specific antigen to predict Gleason upgrading (AUC 0.61 vs 0.57, p = 0.030). Prostate specific antigen density is a significant independent predictor of Gleason upgrading even when accounting for prostate specific antigen. This could be especially important in patients with low risk prostate cancer who seek less invasive therapy such as active surveillance since potentially life threatening disease may be underestimated. Further studies are warranted to help evaluate the role of prostate specific antigen density in Gleason upgrading and its significance for biochemical outcome.

[Bacterial prostatitis and prostatic fibrosis: modern view on the treatment and prophylaxis].

PubMed

Zaitsev, A V; Pushkar, D Yu; Khodyreva, L A; Dudareva, A A

2016-08-01

Treatments of chronic bacterial prostatitis (CP) remain difficult problem. Bacterial prostatitis is a disease entity diagnosed clinically and by evidence of inflammation and infection localized to the prostate. Risk factors for UTI in men include urological interventions, such as transrectal prostate biopsy. Ensuing infections after prostate biopsy, such as UTI and bacterial prostatitis, are increasing due to increasing rates of fluoroquinolone resistance. The increasing global antibiotic resistance also significantly affects management of UTI in men, and therefore calls for alternative strategies. Prostatic inflammation has been suggested to contribute to the etiology of lower urinary tract symptoms (LUTS) by inducing fibrosis. Several studies have shown that prostatic fibrosis is strongly associated with impaired urethral function and LUTS severity. Fibrosis resulting from excessive deposition of collagen is traditionally recognized as a progressive irreversible condition and an end stage of inflammatory diseases; however, there is compelling evidence in both animal and human studies to support that the development of fibrosis could potentially be a reversible process. Prostate inflammation may induce fibrotic changes in periurethral prostatic tissues, promote urethral stiffness and LUTS. Patients experiencing CP and prostate-related LUTS could benefit from anti-inflammatory therapies, especially used in combination with the currently prescribed enzyme treatment with Longidase. Treatment results showed that longidase is highly effective in bacterial and abacterial CP. Longidase addition to standard therapeutic methods significantly reduced the disease symptoms and regression of inflammatory-proliferative alterations in the prostate.

Beyond Seed and Soil: Understanding and Targeting Metastatic Prostate Cancer; Report From the 2016 Coffey-Holden Prostate Cancer Academy Meeting.

PubMed

Miyahira, Andrea K; Roychowdhury, Sameek; Goswami, Sangeeta; Ippolito, Joseph E; Priceman, Saul J; Pritchard, Colin C; Sfanos, Karen S; Subudhi, Sumit K; Simons, Jonathan W; Pienta, Kenneth J; Soule, Howard R

2017-02-01

The 2016 Coffey-Holden Prostate Cancer Academy (CHPCA) Meeting, "Beyond Seed and Soil: Understanding and Targeting Metastatic Prostate Cancer," was held from June 23 to June 26, 2016, in Coronado, California. For the 4th year in a row, the Prostate Cancer Foundation (PCF) hosted the CHPCA Meeting, a think tank-structured scientific conference, which focuses on a specific topic of critical unmet need on the biology and treatment of advanced prostate cancer. The 2016 CHPCA Meeting was attended by 71 investigators from prostate cancer and other fields, who discussed the biology, study methodologies, treatment strategies, and critical unmet needs concerning metastatic prostate cancer, with the ultimate goal of advancing strategies to treat and eliminate this disease. The major topics of discussion included: the molecular landscape and molecular heterogeneity of metastatic prostate cancer, the role of the metastatic microenvironment, optimizing immunotherapy in metastatic prostate cancer, learning from exceptional responders and non-responders, targeting DNA repair deficiency in advanced prostate cancer, developing and applying novel biomarkers and imaging techniques, and potential roles for the microbiome in prostate cancer. This article reviews the topics presented and discussions held at the CHPCA Meeting, with a focus on the unknowns and next steps needed to advance our understanding of the biology and most effective treatment strategies for metastatic prostate cancer. Prostate 77:123-144, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Prostatic fossa gauze-packing in the prevention of blood clot obstruction of the bladder after transvesical prostatectomy.

PubMed

Umunna, J I

2010-01-01

Clot obstruction often complicates transvesical prostatectomy. Any measure that prevents this will be a great relief to both surgeon and patient. To demonstrate that packing the prostatic fossa with roller gauze bandage after transvesical prostatectomy can prevent post-operative clot blockage of bladder drainage . Charts of all patients who had transvesical prostatectomy at Jasman Hospital Udo by me from 1988 to 1997 were sorted into two groups , Group A, not packed and Group B, packed. Information sought included patient's age, type of prostatectomy performed, whether the prostatic fossa was packed or not , average duration of catheter drainage, and complications. There were 68 patients who had no fossa packing and 72 in Group B with fossa packing. The age range of the two groups A and B were respective 45-85 year-old and 50-83 years. In both groups the highest number of patients was in the 60 t0 79 age bracket (48 in group A , 70%, and 56 in group B (78%). Bladder blockage occurred in 32(47%) patients without packing and none (0%) in group B with packing. Average duration of bladder drainage was 14 days in each group. There was no persisting vesico-cutaneous fistula. Temporary urinary incontinence occurred in three (3%) patients who had no packing and in five (7%) with packing. Gauze-packing of the prostatic fossa during transvesical prostatectomy can prevent bladder obstruction from clot retention without undue complications.

Direct ultrasensitive electrical detection of prostate cancer biomarkers with CMOS-compatible n- and p-type silicon nanowire sensor arrays.

PubMed

Gao, Anran; Lu, Na; Dai, Pengfei; Fan, Chunhai; Wang, Yuelin; Li, Tie

2014-11-07

Sensitive and quantitative analysis of proteins is central to disease diagnosis, drug screening, and proteomic studies. Here, a label-free, real-time, simultaneous and ultrasensitive prostate-specific antigen (PSA) sensor was developed using CMOS-compatible silicon nanowire field effect transistors (SiNW FET). Highly responsive n- and p-type SiNW arrays were fabricated and integrated on a single chip with a complementary metal oxide semiconductor (CMOS) compatible anisotropic self-stop etching technique which eliminated the need for a hybrid method. The incorporated n- and p-type nanowires revealed complementary electrical response upon PSA binding, providing a unique means of internal control for sensing signal verification. The highly selective, simultaneous and multiplexed detection of PSA marker at attomolar concentrations, a level useful for clinical diagnosis of prostate cancer, was demonstrated. The detection ability was corroborated to be effective by comparing the detection results at different pH values. Furthermore, the real-time measurement was also carried out in a clinically relevant sample of blood serum, indicating the practicable development of rapid, robust, high-performance, and low-cost diagnostic systems.

Feasibility of minimally invasive radical prostatectomy in prostate cancer patients with high prostate-specific antigen: feasibility and 1-year outcomes.

PubMed

Do, Minh; Ragavan, Narasimhan; Dietel, Anja; Liatsikos, Evangelos; Anderson, Chris; McNeill, Alan; Stolzenburg, Jens-Uwe

2012-10-01

Urologists are cautious to offer minimally invasive radical prostatectomy in prostate cancer patients with high prostate-specific antigen (and therefore anticipated to have locally advanced or metastatic disease) because of concerns regarding lack of complete cure after minimally invasive radical prostatectomy and of worsening of continence if adjuvant radiotherapy is used. A retrospective review of our institutional database was carried out to identify patients with PSA ≥20 ng/mL who underwent minimally invasive radical prostatectomy between January 2002 and October 2010. Intraoperative, pathological, functional and short-term oncological outcomes were assessed. Overall, 233 patients met study criteria and were included in the analysis. The median prostate-specific antigen and prostate size were 28.5 ng/mL and 47 mL, respectively. Intraoperative complications were the following: rectal injury (0.86%) and blood transfusion (1.7%). Early postoperative complications included prolonged (>6 days) catheterization (9.4%), hematoma (4.7%), deep venous thrombosis (0.86%) and lymphocele (5.1%). Late postoperative complications included cerebrovascular accident (0.4%) and anastomotic stricture (0.8%). Pathology revealed poorly differentiated cancer in 48.9%, pT3/pT4 disease in 55.8%, positive margins in 28.3% and lymph node disease in 20.2% of the cases. Adverse pathological findings were more frequent in patients with prostate-specific antigen >40 ng/mL and (or) in those with locally advanced disease (pT3/pT4). In 62.2% of the cases, adjuvant radiotherapy was used. At 1-year follow up, 80% of patients did not show evidence of biochemical recurrence and 98.8% of them had good recovery of continence. Minimally invasive radical prostatectomy might represent a reasonable option in prostate cancer patients with high prostate-specific antigen as a part of a multimodality treatment approach. © 2012 The Japanese Urological Association.

Focal Cryotherapy for Localized Prostate Cancer.

PubMed

Tay, K J; Polascik, T J

2016-07-01

To systematically review the oncological and functional outcomes of contemporary primary prostate focal cryotherapy for localized prostate cancer in the context of current developments in prostate focal therapy. We performed a systematic search of the Pubmed, Cochrane and Embase databases to identify studies where primary prostate focal cryotherapy was performed to treat prostate cancer. These included reports on focal/ lesion/ sector ablation, hemi-ablation and partial prostate ablation. We excluded salvage focal therapy studies. Where multiple reports were published over time from a single cohort, the latest one was used. Our search yielded 290 publications, including 17 primary reports on eight single-center cohort studies and one multi-center registry report. Of 1,595 men identified, mean age was 60.5-69.5 years and mean PSA 5.1-7.8 ng/ml. When stratified by D'Amico risk criteria, 52% of the aggregate total number of men were low-risk, 38% intermediate-risk and 10% high-risk. Besides 12-core TRUS biopsy, 3 cohorts reported using TTMB and one included mpMRI to select men for focal treatment. Median follow-up ranged from 13-63 months. BPFS ranged from 71-98%. The overall post-treatment positive biopsy rate was 8-25%. Among 5 cohorts with a mandatory 6-12 month posttreatment biopsy, 216 of 272 men (79%) did undergo biopsy, with 47 positive (21.8%). Of these, 15 were infield, 26 outfield, 2 bilateral and 4 undeclared. Ten upgraded to Gleason≥7. Overall, two men had metastatic disease and none died of prostate cancer. Post-treatment continence rates were 96-100% and rates of erectile dysfunction ranged from 0-42%. The rate of post-treatment urinary retention ranged from 0-15%. The rate of recto-urethral fistula was 0-0.1%. Focal cryotherapy for localized prostate cancer is a safe and provides good preservation of sexual and urinary function. Accurate cancer localization and risk stratification is key to patient selection. In highly selected patients, focal therapy has good short to medium term oncological efficacy.

Successful percutaneous transperineal drainage of a large prostatic abscess.

PubMed

Mason, Barry M; Hakimi, A Ari; Clerkin, Kevin J; Silva, Jose V

2010-12-01

We present a case of an 83-year-old man with septic shock secondary to an extremely large prostatic abscess. Antibiotics and transperineal percutaneous drainage with a suprapubic-type Malecot catheter successfully treated the abscess. Follow-up images reveal resolution of the abscess. Broad-spectrum antibiotics and drainage permitted a full recovery. Copyright © 2010 Elsevier Inc. All rights reserved.

Ligand, receptor, and cell type-dependent regulation of ABCA1 and ABCG1 mRNA in prostate cancer epithelial cells

USDA-ARS?s Scientific Manuscript database

Recent evidence suggests that the liver X receptor (LXR) is a potential anti-cancer target in prostate carcinoma. There is little characterization, however, of how the two major isoforms LXRa or LXRß regulate the LXR-responsive genes ATP-binding cassette sub-family A 1 (ABCA1) and sub-family member ...