Prostate Cancer Epigenome

PubMed Central

Chinaranagari, Swathi; Sharma, Pankaj; Bowen, Nathan J.; Chaudhary, Jaideep

2018-01-01

Prostate cancer is a major health burden within the ever-increasingly aging US population. The molecular mechanisms involved in prostate cancer are diverse and heterogeneous. In this context, epigenetic changes, both global and gene specific, are now an emerging alternate mechanism in disease initiation and progression. The three major risk factors in prostate cancer: age, geographic ancestry, and environment are all influenced by epigenetics and additional significant insight is required to gain an understanding of the underlying mechanisms. The androgen receptor and its downstream effector pathways, central to prostate cancer initiation and progression, are subject to a multitude of epigenetic alterations. In this review we focus on the global perspective of epigenetics and the use of recent next-generation sequencing platforms to interrogate epigenetic changes in the prostate cancer genome. PMID:25421658

Prostate cancer epigenome.

PubMed

Chinaranagari, Swathi; Sharma, Pankaj; Bowen, Nathan J; Chaudhary, Jaideep

2015-01-01

Prostate cancer is a major health burden within the ever-increasingly aging US population. The molecular mechanisms involved in prostate cancer are diverse and heterogeneous. In this context, epigenetic changes, both global and gene specific, are now an emerging alternate mechanism in disease initiation and progression. The three major risk factors in prostate cancer: age, geographic ancestry, and environment are all influenced by epigenetics and additional significant insight is required to gain an understanding of the underlying mechanisms. The androgen receptor and its downstream effector pathways, central to prostate cancer initiation and progression, are subject to a multitude of epigenetic alterations. In this review we focus on the global perspective of epigenetics and the use of recent next-generation sequencing platforms to interrogate epigenetic changes in the prostate cancer genome.

Utilizing a Narrative Approach to Increasing Intimacy after Prostate Cancer

ERIC Educational Resources Information Center

McCoy, Megan; Stinson, Morgan A.; Bermudez, J. Maria; Gladney, Leslie A.

2013-01-01

Attitudes about sexual intimacy are an important aspect of relationship satisfaction, especially for couples dealing with prostate cancer. Prostate cancer can have profound effects on men and their partners, and more research is needed to better understand potential sexual barriers for these couples. Five major themes identified in the literature…

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.

Epigenetic modifications in prostate cancer.

PubMed

Ngollo, Marjolaine; Dagdemir, Aslihan; Karsli-Ceppioglu, Seher; Judes, Gaelle; Pajon, Amaury; Penault-Llorca, Frederique; Boiteux, Jean-Paul; Bignon, Yves-Jean; Guy, Laurent; Bernard-Gallon, Dominique J

2014-01-01

Prostate cancer is the most common cancer in men and the second leading cause of cancer deaths in men in France. Apart from the genetic alterations in prostate cancer, epigenetics modifications are involved in the development and progression of this disease. Epigenetic events are the main cause in gene regulation and the three most epigenetic mechanisms studied include DNA methylation, histone modifications and microRNA expression. In this review, we summarized epigenetic mechanisms in prostate cancer. Epigenetic drugs that inhibit DNA methylation, histone methylation and histone acetylation might be able to reactivate silenced gene expression in prostate cancer. However, further understanding of interactions of these enzymes and their effects on transcription regulation in prostate cancer is needed and has become a priority in biomedical research. In this study, we summed up epigenetic changes with emphasis on pharmacologic epigenetic target agents.

Prostate cancer family history and eligibility for active surveillance: a systematic review of the literature.

PubMed

Telang, Jaya M; Lane, Brian R; Cher, Michael L; Miller, David C; Dupree, James M

2017-10-01

Active surveillance (AS) is an increasingly prevalent treatment choice for low grade prostate cancer. Eligibility criteria for AS are varied and it is unclear if family history of prostate cancer should be used as an exclusion criterion when considering men for AS. To determine whether family history plays a significant role in the progression of prostate cancer for men undergoing active surveillance, PubMed searches of 'family history and prostate cancer', 'family history and prostate cancer progression' and 'factors of prostate cancer progression' were used to identify research publications about the relationship between family history and prostate cancer progression. These searches generated 536 papers that were screened and reviewed. Six publications were ultimately included in this analysis. Review of the six publications suggests that family history does not increase the risk of prostate cancer progression, whilst a subgroup analysis in one study found that family history increases the risk of prostate cancer progression only in African-Americans. A family history of prostate cancer does not appear to increase a patient's risk of having more aggressive prostate cancer and is therefore unlikely to be an important factor in determining eligibility for AS. Further studies are needed to better understand the relationship between race, family history, and eligibility for AS. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

Understanding your prostate cancer risk

MedlinePlus

... idea to talk with your provider before taking dietary supplements. Some studies have shown that certain supplements may increase the risk for prostate cancer, although this is unproven: Selenium ...

Identifying molecular features for prostate cancer with Gleason 7 based on microarray gene expression profiles.

PubMed

Bălăcescu, Loredana; Bălăcescu, O; Crişan, N; Fetica, B; Petruţ, B; Bungărdean, Cătălina; Rus, Meda; Tudoran, Oana; Meurice, G; Irimie, Al; Dragoş, N; Berindan-Neagoe, Ioana

2011-01-01

Prostate cancer represents the first leading cause of cancer among western male population, with different clinical behavior ranging from indolent to metastatic disease. Although many molecules and deregulated pathways are known, the molecular mechanisms involved in the development of prostate cancer are not fully understood. The aim of this study was to explore the molecular variation underlying the prostate cancer, based on microarray analysis and bioinformatics approaches. Normal and prostate cancer tissues were collected by macrodissection from prostatectomy pieces. All prostate cancer specimens used in our study were Gleason score 7. Gene expression microarray (Agilent Technologies) was used for Whole Human Genome evaluation. The bioinformatics and functional analysis were based on Limma and Ingenuity software. The microarray analysis identified 1119 differentially expressed genes between prostate cancer and normal prostate, which were up- or down-regulated at least 2-fold. P-values were adjusted for multiple testing using Benjamini-Hochberg method with a false discovery rate of 0.01. These genes were analyzed with Ingenuity Pathway Analysis software and were established 23 genetic networks. Our microarray results provide new information regarding the molecular networks in prostate cancer stratified as Gleason 7. These data highlighted gene expression profiles for better understanding of prostate cancer progression.

Castration Resistance in Prostate Cancer Is Mediated by the Kinase NEK6. | Office of Cancer Genomics

Cancer.gov

In prostate cancer, the development of castration resistance is pivotal in progression to aggressive disease. However, understanding of the pathways involved remains incomplete. In this study, we performed a high-throughput genetic screen to identify kinases that enable tumor formation by androgen-dependent prostate epithelial (LHSR-AR) cells under androgen-deprived conditions.

3D Hanging Drop Culture to Establish Prostate Cancer Organoids.

PubMed

Eder, Theresa; Eder, Iris E

2017-01-01

Three-dimensional (3D) cell culture enables the growth of cells in a multidimensional and multicellular manner compared to conventional cell culture techniques. Especially in prostate cancer research there is a big need for more tissue-recapitulating models to get a better understanding of the mechanisms driving prostate cancer as well as to screen for more efficient drugs that can be used for treatment. In this chapter we describe a 3D hanging drop system that can be used to culture prostate cancer organoids as tumor epithelial monocultures and as epithelial-stromal cocultures.

Prostate cancer chemoprevention agent development: the National Cancer Institute, Division of Cancer Prevention portfolio.

PubMed

Parnes, Howard L; House, Margaret G; Kagan, Jacob; Kausal, David J; Lieberman, Ronald

2004-02-01

We describe the current National Cancer Institute chemoprevention agent development program and provide a summary of the intermediate end points used. The National Cancer Institute is currently sponsoring a wide range of studies of promising chemoprevention agents in a variety of informative cohorts, eg high grade prostatic intraepithelial neoplasia, positive family history of cancer, increased prostate specific antigen with negative biopsies, prostate cancer followed expectantly, prostate cancer awaiting definitive therapy and the general population. The rationale for each agent under investigation is derived from epidemiological observations, prostate cancer treatment trials, secondary analyses of large cancer prevention studies, an understanding of cancer biology and prostate carcinogenesis, and/or experimental animal models. Carcinogenesis is a multistep process occurring over decades which is characterized by disruption of the normal regulatory pathways controlling cellular proliferation, programmed cell death and differentiation. Administration of agents to reverse, inhibit or slow this process of malignant transformation is known as chemoprevention. Chemoprevention represents a promising approach to reducing the morbidity and mortality of prostate cancer. A variety of agents are currently being studied in phase 2 clinical trials, some of which may warrant subsequent evaluation in phase 3 trials with definitive cancer end points. Two large phase 3 trials, the Prostate Cancer Prevention Trial and the Selenium and Vitamin E Cancer Prevention Trial, which are ongoing, are also sponsored by the National Cancer Institute.

Micrornas in prostate cancer: an overview.

PubMed

Vanacore, Daniela; Boccellino, Mariarosaria; Rossetti, Sabrina; Cavaliere, Carla; D'Aniello, Carmine; Di Franco, Rossella; Romano, Francesco Jacopo; Montanari, Micaela; La Mantia, Elvira; Piscitelli, Raffaele; Nocerino, Flavia; Cappuccio, Francesca; Grimaldi, Giovanni; Izzo, Alessandro; Castaldo, Luigi; Pepe, Maria Filomena; Malzone, Maria Gabriella; Iovane, Gelsomina; Ametrano, Gianluca; Stiuso, Paola; Quagliuolo, Lucio; Barberio, Daniela; Perdonà, Sisto; Muto, Paolo; Montella, Maurizio; Maiolino, Piera; Veneziani, Bianca Maria; Botti, Gerardo; Caraglia, Michele; Facchini, Gaetano

2017-07-25

Prostate cancer is the second highest cause of cancer mortality after lung tumours. In USA it affects about 2.8 million men and the incidence increases with age in many countries. Therefore, early diagnosis is a very important step for patient clinical evaluation and for a selective and efficient therapy. The study of miRNAs' functions and molecular mechanisms has brought new knowledge in biological processes of cancer. In prostate cancer there is a deregulation of several miRNAs that may function as tumour suppressors or oncogenes. The aim of this review is to analyze the progress made to our understanding of the role of miRNA dysregulation in prostate cancer tumourigenesis.

Love, faith and hope - a secondary analysis of prostate cancer survivors and their partners.

PubMed

O'Shaughnessy, P K; Laws, T A; Esterman, A J

2015-01-01

Men's experience of recovery from treatment for prostate cancer has been extensively researched with reports highlighting the physical side effects of treatments such as erectile dysfunction and incontinence. The psychological, emotional and spiritual burden of prostate cancer on men and their partners has received far less attention. In this study, a secondary thematic analysis of data from a series of separate but related qualitative studies with prostate cancer survivors and their partners was conducted to further explore themes of love, hope and faith within this population. This study identified unresolved needs related to the emotive concepts of love, hope and faith. The findings from this study can be employed to refine psychosocial assessments of men with prostate cancer, and provide a more comprehensive understanding of prostate cancer survivors supportive care needs.

From early detection to rehabilitation in the community: reading beyond the blog testimonies of survivors' quality of life and prostate cancer representation.

PubMed

Zanchetta, Margareth Santos; Cognet, Marguerite; Lam-Kin-Teng, Mary Rachel; Dumitriu, Marie Elisabeth; Renaud, Lise; Rhéaume, Jacques

2016-12-16

Survivors' testimonies can reveal much about men's experiences of prostate cancer and impacts on their quality of life (QOL) during the clinical trajectory of the disease. These survivors' shared thoughts and views were hypothesized to reflect salient features of their lived social representation of prostate cancer. We explored the content of testimonies posted by men to a public blog hosted by a French national prostate cancer patients' association. The study question, "What do French bloggers' testimonies reveal about their lived experiences with prostate cancer, especially regarding their quality of life in community settings, that underpin their social representation of prostate cancer?" guided the exploration and analysis of the textual data. The aims were to better understand men's experiences and predominant thoughts and views, to elucidate patients' behaviours, and to enlighten medical policy and practice. Explore issues of QOL as reported by French prostate cancer survivors in a public blog by: (a) identifying the salient aspects and issues of the experience of living with prostate cancer from the perspective of survivors; and (b) analyzing the content in the posted testimonies regarding perceived and lived impacts of prostate cancer on QOL. A critical ethnographic study guided the selection of textual data from 196 male bloggers' testimonies about prostate cancer posted in the period from 2008 to 2013. Media content analysis method was undertaken on blog testimonies, framed by a multidimensional conceptual framework of QOL. Testimonies focused mainly on medical care and rehabilitation, recovery, health education and self-care, as well as on a global vision of prostate cancer and its impacts on personal views of manhood and masculinity. The language used indicated that political, educative and compassionate discourses were intertwined to create a complex representation of the experience and effects of prostate cancer; this multi-faceted representation can inform the public and professional debate about men's capacity to provide emotional support and problem-solve within a community of interest. Findings, while based on data limited to mostly one-time entries to a French blog, contribute to understanding a unique, collective expression of men's lived experiences of prostate cancer. These anonymous survivors shared their varied reactions, ways of coping, and thoughts on needed change.

Prostate Cancer: A Contemporary Approach to Treatment and Outcomes.

PubMed

Weiner, Adam B; Kundu, Shilajit D

2018-03-01

Given the high incidence of prostate cancer and the need for shared decision-making before screening, it is imperative that primary care providers understand treatment options and treatment adverse effects. In this review article, the treatment options for the localized and metastatic prostate cancer are discussed, including the different modalities and their indications, adverse effects, oncologic outcomes, posttreatment monitoring, and potential treatment options following cancer recurrence. Copyright © 2017 Elsevier Inc. All rights reserved.

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

Understanding Prostate Cancer: Newly Diagnosed

MedlinePlus

... Us The Story of PCF A Legacy of Leadership About the Prostate Cancer Foundation CEO Message Why ... PCF? Support our Partners Annual Report & Financials Our Leadership Leadership Team Board Members Curing Together Patient Stories ...

ERBB2 Increases Metastatic Potentials Specifically in Androgen-Insensitive Prostate Cancer Cells

PubMed Central

Tome-Garcia, Jessica; Li, Dan; Ghazaryan, Seda; Shu, Limin; Wu, Lizhao

2014-01-01

Despite all the blood-based biomarkers used to monitor prostate cancer patients, prostate cancer remains as the second common cause of cancer mortality in men in the United States. This is largely due to a lack of understanding of the molecular pathways that are responsible for the aggressive forms of prostate cancers, the castrate-resistant prostate cancer and the metastatic prostate cancer. Cell signaling pathways activated by the ERBB2 oncogene or the RAS oncogene are frequently found to be altered in metastatic prostate cancers. To evaluate and define the role of the ERBB2/RAS pathway in prostate cancer metastasis, we have evaluated the impact of ERBB2- or RAS-overexpression on the metastatic potentials for four prostate cancer cell lines derived from tumors with different androgen sensitivities. To do so, we transfected the human DU145, LnCaP, and PC3 prostate cancer cells and the murine Myc-CaP prostate cancer cells with the activated form of ERBB2 or H-RAS and assessed their metastatic potentials by three complementary assays, a wound healing assay, a transwell motility assay, and a transwell invasion assay. We showed that while overexpression of ERBB2 increased the metastatic potential of the androgen-insensitive prostate cancer cells (i.e. PC3 and DU145), it did not affect metastatic potentials of the androgen-sensitive prostate cancer cells (i.e. LnCaP and Myc-CaP). In contrast, overexpression of H-RAS only increased the cell motility of Myc-CaP cells, which overexpress the human c-MYC oncogene. Our data suggest that ERBB2 collaborates with androgen signaling to promote prostate cancer metastasis, and that although RAS is one of the critical downstream effectors of ERBB2, it does not phenocopy ERBB2 for its impact on the metastatic potentials of prostate cancer cell lines. PMID:24937171

Highly Disordered Proteins in Prostate Cancer.

PubMed

Uversky, Vladimir N; Na, Insung; Landau, Kevin S; Schenck, Ryan O

2017-01-01

Prostate cancer is one of the major threats to the man's health. There are several mechanisms of the prostate cancer development characterized by the involvement of various androgen-related and androgen-unrelated factors in prostate cancer pathogenesis and in the metastatic carcinogenesis of prostate. In all these processes, proteins play various important roles, and the KEGG database has information on 88 human proteins experimentally shown to be involved in prostate cancer. It is known that many proteins associated with different human maladies are intrinsically disordered (i.e., they do not have stable secondary and/or tertiary structure in their unbound states). The goal of this review is to consider several highly disordered proteins known to be associated with the prostate cancer pathogenesis in order to better understand the roles of disordered proteins in this disease. We also hope that consideration of the pathology-related proteins from the perspective of intrinsic disorder can potentially lead to future experimental studies of these proteins to find novel pathways associated with prostate cancer. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Defining Young in the Context of Prostate Cancer

PubMed Central

Lowe, Anthony; Hyde, Melissa K.; Zajdlewicz, Leah; Gardiner, Robert A.; Sandoe, David; Dunn, Jeff

2015-01-01

The experience of prostate cancer is for most men a major life stress with the psychological burden of this disease falling more heavily on those who are younger. Despite this, being young as it applies to prostate cancer is not yet clearly defined with varied chronological approaches applied. However, men’s responses to health crises are closely bound to life course and masculinities from which social roles emerge. This paper applied qualitative methodology (structured focus groups and semistructured interviews with expert informants) using interpretative phenomenological analysis to define what it means to be young and have prostate cancer. Structured focus groups were held with 26 consumer advisors (men diagnosed with prostate cancer who provide support to other men with prostate cancer or raise community awareness) and health professionals. As well, 15 men diagnosed with prostate cancer and in their 40s, 50s, or 60s participated in semi-structured interviews. Participants discussed the attributes that describe a young man with prostate cancer and the experience of being young and diagnosed with prostate cancer. Chronological definitions of a young man were absent or inconsistent. Masculine constructions of what it means to be a young man and life course characteristics appear more relevant to defining young as it applies to prostate cancer compared with chronological age. These findings have implications for better understanding the morbidities associated with this illness, and in designing interventions that are oriented to life course and helping young men reconstruct their identities after prostate cancer. PMID:24780936

Micrornas in prostate cancer: an overview

PubMed Central

Rossetti, Sabrina; Cavaliere, Carla; D'Aniello, Carmine; Di Franco, Rossella; Romano, Francesco Jacopo; Montanari, Micaela; La Mantia, Elvira; Piscitelli, Raffaele; Nocerino, Flavia; Cappuccio, Francesca; Grimaldi, Giovanni; Izzo, Alessandro; Castaldo, Luigi; Pepe, Maria Filomena; Malzone, Maria Gabriella; Iovane, Gelsomina; Ametrano, Gianluca; Stiuso, Paola; Quagliuolo, Lucio; Barberio, Daniela; Perdonà, Sisto; Muto, Paolo; Montella, Maurizio; Maiolino, Piera; Veneziani, Bianca Maria; Botti, Gerardo; Caraglia, Michele; Facchini, Gaetano

2017-01-01

Prostate cancer is the second highest cause of cancer mortality after lung tumours. In USA it affects about 2.8 million men and the incidence increases with age in many countries. Therefore, early diagnosis is a very important step for patient clinical evaluation and for a selective and efficient therapy. The study of miRNAs' functions and molecular mechanisms has brought new knowledge in biological processes of cancer. In prostate cancer there is a deregulation of several miRNAs that may function as tumour suppressors or oncogenes. The aim of this review is to analyze the progress made to our understanding of the role of miRNA dysregulation in prostate cancer tumourigenesis. PMID:28445135

Gender Role Conflict, Emotional Approach Coping, Self-Compassion and Distress in Prostate Cancer Patients: A Model of Direct and Moderating Effects.

PubMed

Lennon, Jennifer; Hevey, David; Kinsella, Louise

2018-05-14

Gender role conflict or the negative consequences of male socialization may compromise men's adjustment to prostate cancer by shaping how patients perceive and cope with their illness. Given mixed findings regarding how gender role conflict interacts with emotional approach coping to regulate distress in prostate cancer patients, the present study examined the effects of emotional approach coping, when considered alongside self-compassion, the ability to be kind and understanding of oneself. 92 prostate cancer patients completed questionnaires measuring gender role conflict, emotional approach coping, self-compassion and distress. A moderated mediation model was tested, where emotional approach coping mediated the path between gender role conflict and distress and self compassion moderated paths between (a) gender role conflict and emotional approach coping, and (b) gender role conflict and distress. Results partially supported this model with all study variables predicting distress in the expected directions. Emotional approach coping did not mediate associations between gender role conflict and distress; however, self-compassion did moderate the pathway between these variables. Results indicated that higher levels of self-compassion might protect men from distress related to emasculating aspects of the cancer experience. Further investigation is required to understand how self-compassion interacts with emotionality and subsequently influences distress in prostate cancer patients. To better understand the effectiveness of emotional approach coping in reducing distress in prostate cancer patients, it is recommended that future research accounts for the receptiveness of social environments to men's emotional displays. This article is protected by copyright. All rights reserved.

The emerging roles of orphan nuclear receptors in prostate cancer.

PubMed

Wu, Dinglan; Cheung, Alyson; Wang, Yuliang; Yu, Shan; Chan, Franky L

2016-08-01

Orphan nuclear receptors are members of the nuclear receptor (NR) superfamily and are so named because their endogenous physiological ligands are either unknown or may not exist. Because of their important regulatory roles in many key physiological processes, dysregulation of signalings controlled by these receptors is associated with many diseases including cancer. Over years, studies of orphan NRs have become an area of great interest because their specific physiological and pathological roles have not been well-defined, and some of them are promising drug targets for diseases. The recently identified synthetic small molecule ligands, acting as agonists or antagonists, to these orphan NRs not only help to understand better their functional roles but also highlight that the signalings mediated by these ligand-independent NRs in diseases could be therapeutically intervened. This review is a summary of the recent advances in elucidating the emerging functional roles of orphan NRs in cancers, especially prostate cancer. In particular, some orphan NRs, RORγ, TR2, TR4, COUP-IFII, ERRα, DAX1 and SHP, exhibit crosstalk or interference with androgen receptor (AR) signaling in either normal or malignant prostatic cells, highlighting their involvement in prostate cancer progression as androgen and AR signaling pathway play critical roles in this process. We also propose that a better understanding of the mechanism of actions of these orphan NRs in prostate gland or prostate cancer could help to evaluate their potential value as therapeutic targets for prostate cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

Inhibition of CHOP accentuates the apoptotic effect of α-mangostin from the mangosteen fruit (Garcinia mangostana) in 22Rv1 prostate cancer cells.

PubMed

Li, Gongbo; Petiwala, Sakina M; Nonn, Larisa; Johnson, Jeremy J

2014-10-10

The mangosteen (Garcinia mangostana) fruit has been a popular food in Southeast Asia for centuries and is increasing in popularity in Western countries. We identified α-Mangostin as a primary phytochemical modulating ER stress proteins in prostate cancer cells and propose that α-Mangostin is responsible for exerting a biological effect in prostate cancer cells. Two human prostate cancer cell lines, 22Rv1 and LNCaP, and prostate epithelial cells procured from two patients undergoing radical prostatectomy were treated with α-Mangostin and evaluated by RT-PCR, Western blot, fluorescent microscopy and siRNA transfection to evaluate ER stress. Next, we evaluated α-Mangostin for microsomal stability, pharmacokinetic parameters, and anti-cancer activity in nude mice. α-Mangostin significantly upregulated ER stress markers in prostate cancer cells. Interestingly, α-Mangostin did not promote ER stress in prostate epithelial cells (PrECs) from prostate cancer patients. CHOP knockdown enhanced α-Mangostin-induced apoptosis in prostate cancer cells. α-Mangostin significantly suppressed tumor growth in a xenograft tumor model without obvious toxicity. Our study suggests that α-Mangostin is not the only active constituent from the mangosteen fruit requiring further work to understand the complex chemical composition of the mangosteen. Copyright © 2014 Elsevier Inc. All rights reserved.

Activation of β-catenin signaling in androgen receptor-negative prostate cancer cells.

PubMed

Wan, Xinhai; Liu, Jie; Lu, Jing-Fang; Tzelepi, Vassiliki; Yang, Jun; Starbuck, Michael W; Diao, Lixia; Wang, Jing; Efstathiou, Eleni; Vazquez, Elba S; Troncoso, Patricia; Maity, Sankar N; Navone, Nora M

2012-02-01

To study Wnt/β-catenin in castrate-resistant prostate cancer (CRPC) and understand its function independently of the β-catenin-androgen receptor (AR) interaction. We carried out β-catenin immunocytochemical analysis, evaluated TOP-flash reporter activity (a reporter of β-catenin-mediated transcription), and sequenced the β-catenin gene in MDA prostate cancer 118a, MDA prostate cancer 118b, MDA prostate cancer 2b, and PC-3 prostate cancer cells. We knocked down β-catenin in AR-negative MDA prostate cancer 118b cells and carried out comparative gene-array analysis. We also immunohistochemically analyzed β-catenin and AR in 27 bone metastases of human CRPCs. β-Catenin nuclear accumulation and TOP-flash reporter activity were high in MDA prostate cancer 118b but not in MDA prostate cancer 2b or PC-3 cells. MDA prostate cancer 118a and MDA prostate cancer 118b cells carry a mutated β-catenin at codon 32 (D32G). Ten genes were expressed differently (false discovery rate, 0.05) in MDA prostate cancer 118b cells with downregulated β-catenin. One such gene, hyaluronan synthase 2 (HAS2), synthesizes hyaluronan, a core component of the extracellular matrix. We confirmed HAS2 upregulation in PC-3 cells transfected with D32G-mutant β-catenin. Finally, we found nuclear localization of β-catenin in 10 of 27 human tissue specimens; this localization was inversely associated with AR expression (P = 0.056, Fisher's exact test), suggesting that reduced AR expression enables Wnt/β-catenin signaling. We identified a previously unknown downstream target of β-catenin, HAS2, in prostate cancer, and found that high β-catenin nuclear localization and low or no AR expression may define a subpopulation of men with bone metastatic prostate cancer. These findings may guide physicians in managing these patients.

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

Stem cells in prostate cancer initiation and progression

PubMed Central

Lawson, Devon A.; Witte, Owen N.

2007-01-01

Peter Nowell and David Hungerford’s discovery of the Philadelphia chromosome facilitated many critical studies that have led to a paradigm shift in our understanding of cancer as a disease of stem cells. This Review focuses on the application of these concepts to investigation of the role of stem cells in prostate cancer initiation and progression. Major strides in the development of in vitro and in vivo assays have enabled identification and characterization of prostate stem cells as well as functional evaluation of the tumorigenic effects of prostate cancer–related genetic alterations. PMID:17671638

Moving beyond the prostate: benefits in broadening the scope of research on men and cancer.

PubMed

Wenger, Lisa M; Oliffe, John L

2013-03-01

As researchers recognize the value in considering gender dynamics within the cancer experience, a majority of the masculinities work has centered on men with prostate cancer. This focus has positioned prostate cancer as the flagship of men's cancer (and perhaps men's health). There is value in this research. However, as 78% of men experience cancers of a different type, a narrow focus on prostate cancer does not necessarily account for broader intersections of cancer and masculinity. Argued here are the benefits to expanding the focus of research on men's cancer experiences. As researchers consider patterns and diversities among men managing an array of cancers, there is opportunity to broaden understanding of the challenges "cancer" can present for men, disrupt assumptions that the study of men's gendered experience of cancer must be tethered to male sex-specific biology, and enhance the relevance and impact of psychosocial interventions for men living with cancer.

African American Participation in Oncology Clinical Trials--Focus on Prostate Cancer: Implications, Barriers, and Potential Solutions.

PubMed

Ahaghotu, Chiledum; Tyler, Robert; Sartor, Oliver

2016-04-01

In the United States, the incidence and mortality rates of many cancers, especially prostate cancer, are disproportionately high among African American men compared with Caucasian men. Recently, mortality rates for prostate cancer have declined more rapidly in African American versus Caucasian men, but prostate cancer is still the most common cancer and the second leading cause of cancer deaths in African American men in the United States. Compared with Caucasian men, prostate cancer occurs at younger ages, has a higher stage at diagnosis, and is more likely to progress after definitive treatments in African American men. Reasons for racial discrepancies in cancer are multifactorial and potentially include socioeconomic, cultural, nutritional, and biologic elements. In addition to improving access to novel therapies, clinical trial participation is essential to adequately establish the risks and benefits of treatments in African American populations. Considering the disproportionately high mortality rates noted in these groups, our understanding of the natural history and responses to therapies is limited. This review will explore African American underrepresentation in clinical trials with a focus on prostate cancer, and potentially effective strategies to engage African American communities in prostate cancer research. Solutions targeting physicians, investigators, the community, and health care systems are identified. Improvement of African American participation in prostate cancer clinical trials will benefit all stakeholders. Published by Elsevier Inc.

Beta Catenin in Prostate Cancer Apoptosis

DTIC Science & Technology

2011-04-03

understand their role in apoptosis. TRAIL-TZD studies also revealed that pretreatment with a pharmacological inhibitor of GSK3B (AR-A014418) can sensitize...cells potently to TRAIL-induced apoptosis in the absence of TZD. These suggested that the inhibition of GSK3B activity might be the major mechanism by...which TZD sensitizes prostate cancer cells towards TRAIL. GSK3B might thus represent a novel target for developing prostate cancer therapeutics. The in

Human Prostate Cancer Hallmarks Map

PubMed Central

Datta, Dipamoy; Aftabuddin, Md.; Gupta, Dinesh Kumar; Raha, Sanghamitra; Sen, Prosenjit

2016-01-01

Human prostate cancer is a complex heterogeneous disease that mainly affects elder male population of the western world with a high rate of mortality. Acquisitions of diverse sets of hallmark capabilities along with an aberrant functioning of androgen receptor signaling are the central driving forces behind prostatic tumorigenesis and its transition into metastatic castration resistant disease. These hallmark capabilities arise due to an intense orchestration of several crucial factors, including deregulation of vital cell physiological processes, inactivation of tumor suppressive activity and disruption of prostate gland specific cellular homeostasis. The molecular complexity and redundancy of oncoproteins signaling in prostate cancer demands for concurrent inhibition of multiple hallmark associated pathways. By an extensive manual curation of the published biomedical literature, we have developed Human Prostate Cancer Hallmarks Map (HPCHM), an onco-functional atlas of human prostate cancer associated signaling and events. It explores molecular architecture of prostate cancer signaling at various levels, namely key protein components, molecular connectivity map, oncogenic signaling pathway map, pathway based functional connectivity map etc. Here, we briefly represent the systems level understanding of the molecular mechanisms associated with prostate tumorigenesis by considering each and individual molecular and cell biological events of this disease process. PMID:27476486

Gene expression profiling of prostate tissue identifies chromatin regulation as a potential link between obesity and lethal prostate cancer.

PubMed

Ebot, Ericka M; Gerke, Travis; Labbé, David P; Sinnott, Jennifer A; Zadra, Giorgia; Rider, Jennifer R; Tyekucheva, Svitlana; Wilson, Kathryn M; Kelly, Rachel S; Shui, Irene M; Loda, Massimo; Kantoff, Philip W; Finn, Stephen; Vander Heiden, Matthew G; Brown, Myles; Giovannucci, Edward L; Mucci, Lorelei A

2017-11-01

Obese men are at higher risk of advanced prostate cancer and cancer-specific mortality; however, the biology underlying this association remains unclear. This study examined gene expression profiles of prostate tissue to identify biological processes differentially expressed by obesity status and lethal prostate cancer. Gene expression profiling was performed on tumor (n = 402) and adjacent normal (n = 200) prostate tissue from participants in 2 prospective cohorts who had been diagnosed with prostate cancer from 1982 to 2005. Body mass index (BMI) was calculated from the questionnaire immediately preceding cancer diagnosis. Men were followed for metastases or prostate cancer-specific death (lethal disease) through 2011. Gene Ontology biological processes differentially expressed by BMI were identified using gene set enrichment analysis. Pathway scores were computed by averaging the signal intensities of member genes. Odds ratios (ORs) for lethal prostate cancer were estimated with logistic regression. Among 402 men, 48% were healthy weight, 31% were overweight, and 21% were very overweight/obese. Fifteen gene sets were enriched in tumor tissue, but not normal tissue, of very overweight/obese men versus healthy-weight men; 5 of these were related to chromatin modification and remodeling (false-discovery rate < 0.25). Patients with high tumor expression of chromatin-related genes had worse clinical characteristics (Gleason grade > 7, 41% vs 17%; P = 2 × 10 -4 ) and an increased risk of lethal disease that was independent of grade and stage (OR, 5.26; 95% confidence interval, 2.37-12.25). This study improves our understanding of the biology of aggressive prostate cancer and identifies a potential mechanistic link between obesity and prostate cancer death that warrants further study. Cancer 2017;123:4130-4138. © 2017 American Cancer Society. © 2017 American Cancer Society.

Current management of advanced and castration resistant prostate cancer.

PubMed

Gomella, Leonard G; Petrylak, Daniel P; Shayegan, Bobby

2014-04-01

Newer approaches to the management of advanced prostate cancer have rapidly evolved. While basic androgen deprivation remains as the first line in newly diagnosed hormone naïve metastatic prostate cancer, the agents used and strategies followed have undergone significant changes. Numerous new agents such as sipuleucel-T, abiraterone, enzalutamide, cabazitaxel and radium 223 have all been approved since 2010 to treat metastatic castration resistant prostate cancer (CRPC). New imaging techniques to detect advanced disease such as F-18 PET, 11 C-choline PET and other modalities are becoming available. The concepts of "bone health" and the management of side effects related to androgen deprivation therapy are also gaining attention as men are being treated with longer courses of androgen deprivation. Understanding the theory behind these new agents and management approaches while focusing on the practical clinical considerations are essential to improve outcomes in advanced prostate cancer. A review of the current state of the art in the management of advanced and castration resistant prostate cancer presented in this Canadian Journal of Urology International supplement was performed. Key findings are summarized and presented along with critical updates based on recent publications and meeting presentations. Key concepts identified in the management of advanced prostate cancer included the new understanding of prostate cancer based on translational discoveries, applications of various hormonally based strategies in advanced disease including traditional and recently approved agents. The use of new imaging modalities to identify metastatic disease, immunotherapy approaches and discussions of sequencing and which new agents are likely to be available in the future in the management of CRPC were identified. Bone targeted strategies are also addressed in the setting of androgen deprivation and metastatic disease. The management of men with advanced prostate cancer has become more multidisciplinary as treatment options have expanded. As the use of these agents and new strategies expand, urologists, medical oncologists and radiation oncologists must all become familiar with this rapidly changing field in order to maximize the outcome of patients with advanced and castration resistant prostate cancer.

Perspectives on the clinical development of immunotherapy in prostate cancer.

PubMed

Cordes, Lisa M; Gulley, James L; Madan, Ravi A

2018-01-01

Despite impressive survival benefits with immunotherapy in patients with various solid tumors, the full potential of these agents in prostate cancer has yet to be realized. Sipuleucel-T demonstrated a survival benefit in this population, indicating that prostate cancer is an immunoresponsive disease; however, these results have not been matched by other agents. A large trial with ipilimumab in prostate cancer failed to meet its primary objective, and small trials with PD-1/PD-L1 inhibitors did not yield a significant improvement in overall response. However, several late-stage clinical trials are underway with other vaccines in prostate cancer. Reports of clinical benefit with immunotherapies, particularly when used in combination or a select population, have provided the framework to develop sound clinical trials. Understanding immunogenic modulation, antigen spread, biomarkers, and DNA-repair defects will also help mold future strategies. Through rational patient selection and evidence-based combination approaches, patients with prostate cancer may soon derive durable survival benefits with immunotherapies.

Probing the prostate tumour microenvironment I: impact of glucose deprivation on a cell model of prostate cancer progression

PubMed Central

Tonry, Claire; Armstrong, John; Pennington, Stephen R.

2017-01-01

In the developed world, prostate cancer is the most common cancer diagnosis in men. Although prostate cancer initially presents as a non life-threatening disease, 90% of patients will develop castration resistant prostate cancer (CRPC), which preludes distant metastasis and is largely accountable for prostate cancer associated deaths. This is because as yet, there are no viable molecular therapeutic targets for effective treatment of CRPC. It is now widely accepted that cancer cells can alter their metabolic profile during the course of tumourgenesis and metastasis such that they are able to survive in oxygen and nutrient-poor environments. This work was aimed towards gaining greater mechanistic understanding of how such stresses in the tumour microenvironment impact on both androgen sensitive (LNCaP) and androgen independent (LNCaP-abl and LNCaP-abl-Hof) prostate cancer cell lines. Here we have applied technically robust and reproducible label-free liquid chromatography mass spectrometry analysis for comprehensive proteomic profiling of prostate cancer cell lines under nutrient deficient (low glucose) conditions. This led to the identification of approximately 4,000 proteins - one of the largest protein datasets for prostate cancer cell lines established to date. The biological and clinical significance of proteins showing a significant change in expression as result of low glucose conditions was established. Novel, intuitive workflows were subsequently implemented to ensure the verification of selected proteins of interest in a robust, reproducible and high throughput manner. Overall, these data suggest that this strategy supports identification of protein biomarkers of prostate cancer progression and potential therapeutic targets for CRPC. PMID:28086232

hsa-miR-135a-1 inhibits prostate cancer cell growth and migration by targeting EGFR.

PubMed

Xu, Bin; Tao, Tao; Wang, Yiduo; Fang, Fang; Huang, Yeqing; Chen, Shuqiu; Zhu, Weidong; Chen, Ming

2016-10-01

Prostate cancer is one of the leading causes of death in men worldwide. Differentially expressed microRNAs (miRNAs) are associated with metastatic prostate cancer. However, their potential roles for affecting prostate cancer initiation and progression remain largely unknown. Here, we examined the aberrant expression profiles of miRNAs in human metastatic prostate cancer tissues. We further validated our miRNA expression data using two large, independent clinical prostate cancer datasets from the Memorial Sloan Kettering Cancer Center (MSKCC) and The Cancer Genome Atlas (TCGA). Our data support a model in which hsa-miR-135-1 acts as a potential tumor suppressor in metastatic prostate cancer. First, its downregulation was positively correlated with late TNM stage, high Gleason score, and adverse prognosis. Second, cell growth, cell cycle progression, cell migration and invasion, and xenograft tumor formation were dramatically inhibited by miR-135a overexpression. Third, in the microarray gene expression data analysis using Gene Set Enrichment Analysis (GSEA), Database for Annotation, Visualization and Integrated Discovery (DAVID) analysis, Ingenuity Pathway Analysis (IPA), and Oncomine concept analysis, we showed that miR-135a targets multiple oncogenic pathways including epidermal growth factor receptor (EGFR), which we verified using functional experimental assays. These results help advance our understanding of the function of miRNAs in metastatic prostate cancer and provide a basis for further clinical investigation.

The biology and natural history of prostate cancer: a short introduction.

PubMed

Holmberg, Lars; Van Hemelrijck, Mieke

2014-01-01

This chapter aims to serve as a quick glance outlining an overall picture of mainstream thoughts, and to serve as a point of departure for more thorough discussions. The introduction of PSA testing has immensely complicated research in prostate cancer epidemiology and biology and added new clinical and biological domains. As for many cancers, age and ethnic origin are the strongest known risk factors. While migrant studies imply that environment and/or personal life style is important, epidemiological studies have failed to establish any strong leads. Despite the known androgen dependence of prostate cancer, there is little to support that circulating levels of androgens, estrogens or 5-alpha-reductase are associated with risk of developing the disease. However, a consistent finding is a positive association with levels of Insulin-like Growth Factor-1 (IGF-1). Prostate cancer is one of the cancers most strongly related to inherited susceptibility, even when taking into account that family history of prostate cancer triggers PSA testing among relatives. A number of somatic genetic alterations (amplifications, deletions, point mutations, translocations) are associated with prostate cancer risk. Findings for alterations in FASN, HPN, AMACR and MYC have been fairly consistent. Recent research shows that the notion of "hormone-independent prostate cancer" has to be revised: most prostate cancers remain dependent on androgen receptor signalling also after progression despite traditional androgen deprivation therapy. Traditional markers of stage and type of disease still play a major role for prognostication and treatment decisions. Prostate cancer is one of the few cancers where patients have been recommended watchful waiting or active surveillance. This provides opportunities for studies of natural history of the disease. The understanding of prostate cancer aetiology and natural history has progressed slowly. However, the current situation is positively challenging and opens up possibilities for fruitful research.

Genistein and daidzein: different molecular effects on prostate cancer.

PubMed

Adjakly, Mawussi; Ngollo, Marjolaine; Boiteux, Jean-Paul; Bignon, Yves-Jean; Guy, Laurent; Bernard-Gallon, Dominique

2013-01-01

Diet is believed to play an important role in cancer. It has been revealed by epidemiological studies that Asian populations, who consume phytoestrogens in large amounts, have a lower incidence of prostate cancer in comparison with the Western world, where consumption of soy is lower. Genistein and daidzein, the soy phytoestrogens most widely studied, are believed to be potent anticancer agents and have been shown to possess anticancer properties. It has been shown that these compounds inhibit the growth of cancer cells through the modulation of genes controlling cell-cycle progression. Genistein inhibits the activation of the kappa light polypeptide gene enhancer in B-cells (NF-κB), signaling pathway, which is implicated in the balance between cell survival and programmed cell death (apoptosis). Antioxidant and antiangiogenesis properties of genistein have been also described. Soy isoflavones are also implicated in reversion of epigenetic events observed in prostate cancer. Significant advances have been made for understanding how soy isoflavones are implicated in protection against prostate cancer. However, more studies are needed to better-understand and elucidate all pathways mobilized by genistein and daidzein, in order to fully exploit their anticancer properties.

Radio-sensitizing Effects of Novel Histone De-Acetylase Inhibitors in Prostate Cancer

DTIC Science & Technology

2007-03-01

were investigated in PC-3, LN -3 and DU-145 cells. (S)-HDAC-42 and SAHA could sensitize PC-3 and DU-145 cells to radiation. Aim 2: Effects of VAD- 18 ...combined effects of HDAC inhibitors and ionizing radiation on prostate cancer cell lines (PC-3, LN -3, LnCAP, DU-145 and 22Rv1). Aim 2. To understand the...cancer cell lines. Aim 3. To determine the combined effects of HDAC inhibitors plus ionizing radiation on the regression of (i) prostate cancer xenografts

[Immunotherapy: a therapeutic revolution against prostate cancer?].

PubMed

Pracht, Marc; Herrera, Fernanda; Tawadros, Thomas; Berthold, Dominik

2013-05-22

The interaction between the immune system and cancer was an area of research interest for several decades. The recent U.S. Food and Drug Administration approval of sipuleucel-T and ipilimumab stimulated broader interest in manipulating immunity to fight cancer. In the context of prostate cancer, the immunotherapy strategies under development are therapeutic vaccination strategies, such as sipuleucel-T and PROSTVAC-VF, or immune checkpoint blockade of CTLA-4. Improved understanding of the immune responses generated by the development of predictive biomarkers for patient selection will guide rational combinations of these treatments and provide new treatment options in prostate cancer.

Molecular pathways and targets in prostate cancer

PubMed Central

Shtivelman, Emma; Beer, Tomasz M.; Evans, Christopher P.

2014-01-01

Prostate cancer co-opts a unique set of cellular pathways in its initiation and progression. The heterogeneity of prostate cancers is evident at earlier stages, and has led to rigorous efforts to stratify the localized prostate cancers, so that progression to advanced stages could be predicted based upon salient features of the early disease. The deregulated androgen receptor signaling is undeniably most important in the progression of the majority of prostate tumors. It is perhaps because of the primacy of the androgen receptor governed transcriptional program in prostate epithelium cells that once this program is corrupted, the consequences of the ensuing changes in activity are pleotropic and could contribute to malignancy in multiple ways. Following localized surgical and radiation therapies, 20-40% of patients will relapse and progress, and will be treated with androgen deprivation therapies. The successful development of the new agents that inhibit androgen signaling has changed the progression free survival in hormone resistant disease, but this has not changed the almost ubiquitous development of truly resistant phenotypes in advanced prostate cancer. This review summarizes the current understanding of the molecular pathways involved in localized and metastatic prostate cancer, with an emphasis on the clinical implications of the new knowledge. PMID:25277175

Atmospheric Pressure Photoionization Tandem Mass Spectrometry of Androgens in Prostate Cancer

PubMed Central

Lih, Fred Bjørn; Titus, Mark A.; Mohler, James L.; Tomer, Kenneth B.

2010-01-01

Androgen deprivation therapy is the most common treatment option for advanced prostate cancer. Almost all prostate cancers recur during androgen deprivation therapy, and new evidence suggests that androgen receptor activation persists despite castrate levels of circulating androgens. Quantitation of tissue levels of androgens is critical to understanding the mechanism of recurrence of prostate cancer during androgen deprivation therapy. A liquid chromatography atmospheric pressure photoionization tandem mass spectrometric method was developed for quantitation of tissue levels of androgens. Quantitation of the saturated keto-steroids dihydrotestosterone and 5-α-androstanedione required detection of a novel parent ion, [M + 15]+. The nature of this parent ion was explored and the method applied to prostate tissue and cell culture with comparison to results achieved using electrospray ionization. PMID:20560527

Curcumin Attenuates β-catenin Signaling in Prostate Cancer Cells through Activation of Protein Kinase D1

PubMed Central

Sundram, Vasudha; Chauhan, Subhash C.; Ebeling, Mara; Jaggi, Meena

2012-01-01

Prostate cancer is the most commonly diagnosed cancer affecting 1 in 6 males in the US. Understanding the molecular basis of prostate cancer progression can serve as a tool for early diagnosis and development of novel treatment strategies for this disease. Protein Kinase D1 (PKD1) is a multifunctional kinase that is highly expressed in normal prostate. The decreased expression of PKD1 has been associated with the progression of prostate cancer. Therefore, synthetic or natural products that regulate this signaling pathway can serve as novel therapeutic modalities for prostate cancer prevention and treatment. Curcumin, the active ingredient of turmeric, has shown anti-cancer properties via modulation of a number of different molecular pathways. Herein, we have demonstrated that curcumin activates PKD1, resulting in changes in β-catenin signaling by inhibiting nuclear β-catenin transcription activity and enhancing the levels of membrane β-catenin in prostate cancer cells. Modulation of these cellular events by curcumin correlated with decreased cell proliferation, colony formation and cell motility and enhanced cell-cell aggregation in prostate cancer cells. In addition, we have also revealed that inhibition of cell motility by curcumin is mediated by decreasing the levels of active cofilin, a downstream target of PKD1. The potent anti-cancer effects of curcumin in vitro were also reflected in a prostate cancer xenograft mouse model. The in vivo inhibition of tumor growth also correlated with enhanced membrane localization of β-catenin. Overall, our findings herein have revealed a novel molecular mechanism of curcumin action via the activation of PKD1 in prostate cancer cells. PMID:22523587

Testosterone Therapy in Men With Prostate Cancer

PubMed Central

Kaplan, Alan L.; Hu, Jim C.; Morgentaler, Abraham; Mulhall, John P.; Schulman, Claude C.; Montorsi, Francesco

2016-01-01

Context The use of testosterone therapy in men with prostate cancer was previously contraindicated, although recent data challenge this axiom. Over the past 2 decades, there has been a dramatic paradigm shift in beliefs, attitude, and treatment of testosterone deficiency in men with prostate cancer. Objective To summarize and analyze current literature regarding the effect of testosterone replacement in men with prostate cancer. Evidence acquisition We conducted a Medline search to identify all publications related to testosterone therapy in both treated and untreated prostate cancer. Evidence synthesis The historical notion that increasing testosterone was responsible for prostate cancer growth was based on elegant yet limited studies from the 1940s and anecdotal case reports. Current evidence reveals that high endogenous androgen levels do not increase the risk of a prostate cancer diagnosis. Similarly, testosterone therapy in men with testosterone deficiency does not appear to increase prostate cancer risk or the likelihood of a more aggressive disease at prostate cancer diagnosis. Androgen receptor saturation (the saturation model) appears to account for this phenomenon. Men who received testosterone therapy after treatment for localized prostate cancer do not appear to suffer higher rates of recurrence or worse outcomes; although studies to date are limited. Early reports of men on active surveillance/watchful waiting treated with testosterone have not identified adverse progression events. Conclusions An improved understanding of the negative effects of testosterone deficiency on health and health-related quality of life—and the ability of testosterone therapy to mitigate these effects—has triggered a re-evaluation of the role testosterone plays in prostate cancer. An important paradigm shift has occurred within the field, in which testosterone therapy may now be regarded as a viable option for selected men with prostate cancer suffering from testosterone deficiency. Patient summary In this article, we review and summarize the existing literature surrounding the use of testosterone therapy in men with prostate cancer. Historically, testosterone was contraindicated in men with a history of prostate cancer. We show that this contraindication is unfounded and, with careful monitoring, its use is safe in that regard. PMID:26719015

Molecular profiles of finasteride effects on prostate carcinogenesis.

PubMed

Li, Jin; Kim, Jeri

2009-06-01

Our inability to distinguish between low-grade prostate cancers that pose no threat and those that can kill compels newly diagnosed early prostate cancer patients to make decisions that may negatively affect their lives needlessly for years afterward. To reliably stratify patients into different risk categories and apply appropriate treatment, we need a better molecular understanding of prostate cancer progression. Androgen ablation therapy and 5-alpha reductase inhibitors reduce dihydrotestosterone levels and increase apoptosis. Because of the differing biological potentials of tumor cells, however, these treatments may, in some cases, worsen outcome by selecting for or inducing adaptation of stronger androgen receptor signaling pathways. Reduced dihydrotestosterone also may be associated with altered survival pathways. Complicating treatment effects further, molecular adaptation may be accelerated by interactions between epithelial and stromal cells. The hypothesis that early prostate cancer cells with differing biological potential may respond differently to finasteride treatment is worth testing. Ongoing studies using a systems biology approach in a preoperative prostate cancer setting are testing this hypothesis toward developing more-rational clinical interventions.

The role of epithelial plasticity in prostate cancer dissemination and treatment resistance

PubMed Central

Bitting, Rhonda L.; Schaeffer, Daneen; Somarelli, Jason A.; Garcia-Blanco, Mariano A.

2014-01-01

Nearly 30,000 men die annually in the USA of prostate cancer, nearly uniformly from metastatic dissemination. Despite recent advances in hormonal, immunologic, bone-targeted, and cytotoxic chemotherapies, treatment resistance and further dissemination are inevitable in men with metastatic disease. Emerging data suggests that the phenomenon of epithelial plasticity, encompassing both reversible mesenchymal transitions and acquisition of stemness traits, may underlie this lethal biology of dissemination and treatment resistance. Understanding the molecular underpinnings of this cellular plasticity from preclinical models of prostate cancer and from biomarker studies of human metastatic prostate cancer has provided clues to novel therapeutic approaches that may delay or prevent metastatic disease and lethality over time. This review will discuss the preclinical and clinical evidence for epithelial plasticity in this rapidly changing field and relate this to clinical phenotype and resistance in prostate cancer while suggesting novel therapeutic approaches. PMID:24414193

Impact of the United States Preventive Services Task Force 'D' recommendation on prostate cancer screening and staging.

PubMed

Eapen, Renu S; Herlemann, Annika; Washington, Samuel L; Cooperberg, Matthew R

2017-05-01

In 2012, the United States Preventive Services Task Force (USPSTF) issued a grade 'D' recommendation against the use of routine prostate-specific antigen (PSA)-based screening for any men. This recommendation reflects critical misinterpretations of the available evidence base regarding benefits and harms of PSA screening and has influenced the nationwide landscape of prostate cancer screening, diagnosis, and treatment. Following the USPSTF recommendation, a substantial decline in PSA screening was noted for all age groups. Similarly, overall rates of prostate biopsy and prostate cancer incidence have significantly decreased with a shift toward higher grade and stage disease upon diagnosis. Concurrently, the incidence of metastatic prostate cancer has significantly risen in the United States. These trends are concerning particularly for the younger men with occult high-grade disease who are expected to benefit the most from early detection and definitive prostate cancer treatment. These emerging trends in PSA screening and prostate cancer incidence following the USPSTF recommendation may have significant public health implications. Due to the long natural history of the disease, a long-term follow-up is needed to provide a better understanding on the implications of such recommendations on disease progression and mortality rates in prostate cancer patients. The future of US screening policy should reflect a targeted 'smarter' screening strategy rather than dichotomizing the decision between 'screen all' or 'screen none'.

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

Men of African Descent and Carcinoma of the Prostate Consortium

Cancer.gov

The Men of African Descent and Carcinoma of the Prostate Consortium collaborates on epidemiologic studies to address the high burden of prostate cancer and to understand the causes of etiology and outcomes among men of African ancestry.

Exogenous fatty acid binding protein 4 promotes human prostate cancer cell progression.

PubMed

Uehara, Hisanori; Takahashi, Tetsuyuki; Oha, Mina; Ogawa, Hirohisa; Izumi, Keisuke

2014-12-01

Epidemiologic studies have found that obesity is associated with malignant grade and mortality in prostate cancer. Several adipokines have been implicated as putative mediating factors between obesity and prostate cancer. Fatty acid binding protein 4 (FABP4), a member of the cytoplasmic fatty acid binding protein multigene family, was recently identified as a novel adipokine. Although FABP4 is released from adipocytes and mean circulating concentrations of FABP4 are linked with obesity, effects of exogenous FABP4 on prostate cancer progression are unclear. In this study, we examined the effects of exogenous FABP4 on human prostate cancer cell progression. FABP4 treatment promoted serum-induced prostate cancer cell invasion in vitro. Furthermore, oleic acid promoted prostate cancer cell invasion only if FABP4 was present in the medium. These promoting effects were reduced by FABP4 inhibitor, which inhibits FABP4 binding to fatty acids. Immunostaining for FABP4 showed that exogenous FABP4 was taken up into DU145 cells in three-dimensional culture. In mice, treatment with FABP4 inhibitor reduced the subcutaneous growth and lung metastasis of prostate cancer cells. Immunohistochemical analysis showed that the number of apoptotic cells, positive for cleaved caspase-3 and cleaved PARP, was increased in subcutaneous tumors of FABP4 inhibitor-treated mice, as compared with control mice. These results suggest that exogenous FABP4 might promote human prostate cancer cell progression by binding with fatty acids. Additionally, exogenous FABP4 activated the PI3K/Akt pathway, independently of binding to fatty acids. Thus, FABP4 might be a key molecule to understand the mechanisms underlying the obesity-prostate cancer progression link. © 2014 UICC.

Health Changes in Low Income Men Transitioning from a State Funded Prostate Cancer Program to Comprehensive Insurance.

PubMed

Nabhani, Jamal A; Kuang, Ruby; Liu, Hui; Kwan, Lorna; Litwin, Mark S

2018-07-01

We evaluated the effect of transitioning from a prostate cancer specific treatment program to comprehensive insurance under the ACA (Patient Protection and Affordable Care Act) on the physical, mental and prostate cancer related health of poor, previously uninsured men. We assessed general and prostate cancer specific health related quality of life using the RAND SF-12v2™ (12-Item Short Form Survey, version 2) and the UCLA PCI (Prostate Cancer Index) at 3 time points in 24 men who transitioned to comprehensive insurance as the insured group relative to 39 who remained in the prostate cancer program as the control group. We used mixed effects models controlling for treatment and patient factors to measure health differences between the groups during the transition period. Demographics, prostate cancer treatment patterns, and mental, physical and general health were similar before transition in the control and insured groups. After transition men who gained insurance coverage reported significantly worse physical health than men who remained in the prostate cancer program (p = 0.0038). After adjustment in the mixed effects model physical health remained worse in men who gained insurance (p = 0.0036). Mental health and prostate cancer related quality of life did not differ with time between the groups. Compared to controls who remained in the state funded prostate cancer treatment program for poor, uninsured men, newly insured men reported worse physical health after transitioning to ACA coverage. Providers and policy makers may draw important lessons from understanding the mechanisms of this paradoxical worsening in physical health after gaining insurance. These results inform the development of disease specific models of care in the broader health insurance context. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Pan-Cancer Analysis of the Mediator Complex Transcriptome Identifies CDK19 and CDK8 as Therapeutic Targets in Advanced Prostate Cancer.

PubMed

Brägelmann, Johannes; Klümper, Niklas; Offermann, Anne; von Mässenhausen, Anne; Böhm, Diana; Deng, Mario; Queisser, Angela; Sanders, Christine; Syring, Isabella; Merseburger, Axel S; Vogel, Wenzel; Sievers, Elisabeth; Vlasic, Ignacija; Carlsson, Jessica; Andrén, Ove; Brossart, Peter; Duensing, Stefan; Svensson, Maria A; Shaikhibrahim, Zaki; Kirfel, Jutta; Perner, Sven

2017-04-01

Purpose: The Mediator complex is a multiprotein assembly, which serves as a hub for diverse signaling pathways to regulate gene expression. Because gene expression is frequently altered in cancer, a systematic understanding of the Mediator complex in malignancies could foster the development of novel targeted therapeutic approaches. Experimental Design: We performed a systematic deconvolution of the Mediator subunit expression profiles across 23 cancer entities ( n = 8,568) using data from The Cancer Genome Atlas (TCGA). Prostate cancer-specific findings were validated in two publicly available gene expression cohorts and a large cohort of primary and advanced prostate cancer ( n = 622) stained by immunohistochemistry. The role of CDK19 and CDK8 was evaluated by siRNA-mediated gene knockdown and inhibitor treatment in prostate cancer cell lines with functional assays and gene expression analysis by RNAseq. Results: Cluster analysis of TCGA expression data segregated tumor entities, indicating tumor-type-specific Mediator complex compositions. Only prostate cancer was marked by high expression of CDK19 In primary prostate cancer, CDK19 was associated with increased aggressiveness and shorter disease-free survival. During cancer progression, highest levels of CDK19 and of its paralog CDK8 were present in metastases. In vitro , inhibition of CDK19 and CDK8 by knockdown or treatment with a selective CDK8/CDK19 inhibitor significantly decreased migration and invasion. Conclusions: Our analysis revealed distinct transcriptional expression profiles of the Mediator complex across cancer entities indicating differential modes of transcriptional regulation. Moreover, it identified CDK19 and CDK8 to be specifically overexpressed during prostate cancer progression, highlighting their potential as novel therapeutic targets in advanced prostate cancer. Clin Cancer Res; 23(7); 1829-40. ©2016 AACR . ©2016 American Association for Cancer Research.

Androgen receptor: structure, role in prostate cancer and drug discovery

PubMed Central

Tan, MH Eileen; Li, Jun; Xu, H Eric; Melcher, Karsten; Yong, Eu-leong

2015-01-01

Androgens and androgen receptors (AR) play a pivotal role in expression of the male phenotype. Several diseases, such as androgen insensitivity syndrome (AIS) and prostate cancer, are associated with alterations in AR functions. Indeed, androgen blockade by drugs that prevent the production of androgens and/or block the action of the AR inhibits prostate cancer growth. However, resistance to these drugs often occurs after 2–3 years as the patients develop castration-resistant prostate cancer (CRPC). In CRPC, a functional AR remains a key regulator. Early studies focused on the functional domains of the AR and its crucial role in the pathology. The elucidation of the structures of the AR DNA binding domain (DBD) and ligand binding domain (LBD) provides a new framework for understanding the functions of this receptor and leads to the development of rational drug design for the treatment of prostate cancer. An overview of androgen receptor structure and activity, its actions in prostate cancer, and how structural information and high-throughput screening have been or can be used for drug discovery are provided herein. PMID:24909511

NPM1 Silencing Reduces Tumour Growth and MAPK Signalling in Prostate Cancer Cells

PubMed Central

Loubeau, Gaëlle; Boudra, Rafik; Maquaire, Sabrina; Lours-Calet, Corinne; Beaudoin, Claude; Verrelle, Pierre; Morel, Laurent

2014-01-01

The chaperone nucleophosmin (NPM1) is over-expressed in the epithelial compartment of prostate tumours compared to adjacent healthy epithelium and may represent one of the key actors that support the neoplastic phenotype of prostate adenocarcinoma cells. Yet, the mechanisms that underlie NPM1 mediated phenotype remain elusive in the prostate. To better understand NPM1 functions in prostate cancer cells, we sought to characterize its impact on prostate cancer cells behaviour and decipher the mechanisms by which it may act. Here we show that NPM1 favors prostate tumour cell migration, invasion and colony forming. Furthermore, knockdown of NPM1 leads to a decrease in the growth of LNCaP-derived tumours grafted in Nude mice in vivo. Such oncogenic-like properties are found in conjunction with a positive regulation of NPM1 on the ERK1/2 (Extracellular signal-Regulated Kinases 1/2) kinase phosphorylation in response to EGF (Epidermal Growth Factor) stimulus, which is critical for prostate cancer progression following the setting of an autonomous production of the growth factor. NPM1 could then be a target to switch off specifically ERK1/2 pathway activation in order to decrease or inhibit cancer cell growth and migration. PMID:24796332

A Model for Understanding the Genetic Basis for Disparity in Prostate Cancer Risk

DTIC Science & Technology

2017-10-01

times greater compared with European American men. The reasons for this disparity are not completely understood. Current tools in hand to study these...from iPSC of Caucasian and African-American foreskin fibroblasts and 3) compare and establish methods to transform differentiated prostate epithelial...NOT include the italicized descriptions of section contents in your submitted reports. 1. INTRODUCTION: Prostate cancer is the most commonly diagnosed

Analysis of the spatial distribution of prostate cancer obtained from histopathological images

NASA Astrophysics Data System (ADS)

Diaz, Kristians; Castaneda, Benjamin; Montero, Maria Luisa; Yao, Jorge; Joseph, Jean; Rubens, Deborah; Parker, Kevin J.

2013-03-01

Understanding the spatial distribution of prostate cancer and how it changes according to prostate specific antigen (PSA) values, Gleason score, and other clinical parameters may help comprehend the disease and increase the overall success rate of biopsies. This work aims to build 3D spatial distributions of prostate cancer and examine the extent and location of cancer as a function of independent clinical parameters. The border of the gland and cancerous regions from wholemount histopathological images are used to reconstruct 3D models showing the localization of tumor. This process utilizes color segmentation and interpolation based on mathematical morphological distance. 58 glands are deformed into one prostate atlas using a combination of rigid, affine, and b-spline deformable registration techniques. Spatial distribution is developed by counting the number of occurrences in a given position in 3D space from each registered prostate cancer. Finally a difference between proportions is used to compare different spatial distributions. Results show that prostate cancer has a significant difference (SD) in the right zone of the prostate between populations with PSA greater and less than 5ng/ml. Age does not have any impact in the spatial distribution of the disease. Positive and negative capsule-penetrated cases show a SD in the right posterior zone. There is SD in almost all the glands between cases with tumors larger and smaller than 10% of the whole prostate. A larger database is needed to improve the statistical validity of the test. Finally, information from whole-mount histopathological images may provide better insight into prostate cancer.

Probing the prostate tumour microenvironment II: Impact of hypoxia on a cell model of prostate cancer progression

PubMed Central

Tonry, Claire; Armstrong, John; Pennington, Stephen

2017-01-01

Approximately one in six men are diagnosed with Prostate Cancer every year in the Western world. Although it can be well managed and non-life threatening in the early stages, over time many patients cease to respond to treatment and develop castrate resistant prostate cancer (CRPC). CRPC represents a clinically challenging and lethal form of prostate cancer. Progression of CRPC is, in part, driven by the ability of cancer cells to alter their metabolic profile during the course of tumourgenesis and metastasis so that they can survive in oxygen and nutrient-poor environments and even withstand treatment. This work was carried out as a continuation of a study aimed towards gaining greater mechanistic understanding of how conditions within the tumour microenvironment impact on both androgen sensitive (LNCaP) and androgen independent (LNCaP-abl and LNCaP-abl-Hof) prostate cancer cell lines. Here we have applied technically robust and reproducible label-free liquid chromatography mass spectrometry analysis for comprehensive proteomic profiling of prostate cancer cell lines under hypoxic conditions. This led to the identification of over 4,000 proteins – one of the largest protein datasets for prostate cancer cell lines established to date. The biological and clinical significance of proteins showing a significant change in expression as result of hypoxic conditions was established. Novel, intuitive workflows were subsequently implemented to enable robust, reproducible and high throughput verification of selected proteins of interest. Overall, these data suggest that this strategy supports identification of protein biomarkers of prostate cancer progression and potential therapeutic targets for CRPC. PMID:28410543

Characterizing Genetic Risk at Known Prostate Cancer Susceptibility Loci in African Americans

PubMed Central

Haiman, Christopher A.; Chen, Gary K.; Blot, William J.; Strom, Sara S.; Berndt, Sonja I.; Kittles, Rick A.; Rybicki, Benjamin A.; Isaacs, William B.; Ingles, Sue A.; Stanford, Janet L.; Diver, W. Ryan; Witte, John S.; Chanock, Stephen J.; Kolb, Suzanne; Signorello, Lisa B.; Yamamura, Yuko; Neslund-Dudas, Christine; Thun, Michael J.; Murphy, Adam; Casey, Graham; Sheng, Xin; Wan, Peggy; Pooler, Loreall C.; Monroe, Kristine R.; Waters, Kevin M.; Le Marchand, Loic; Kolonel, Laurence N.; Stram, Daniel O.; Henderson, Brian E.

2011-01-01

GWAS of prostate cancer have been remarkably successful in revealing common genetic variants and novel biological pathways that are linked with its etiology. A more complete understanding of inherited susceptibility to prostate cancer in the general population will come from continuing such discovery efforts and from testing known risk alleles in diverse racial and ethnic groups. In this large study of prostate cancer in African American men (3,425 prostate cancer cases and 3,290 controls), we tested 49 risk variants located in 28 genomic regions identified through GWAS in men of European and Asian descent, and we replicated associations (at p≤0.05) with roughly half of these markers. Through fine-mapping, we identified nearby markers in many regions that better define associations in African Americans. At 8q24, we found 9 variants (p≤6×10−4) that best capture risk of prostate cancer in African Americans, many of which are more common in men of African than European descent. The markers found to be associated with risk at each locus improved risk modeling in African Americans (per allele OR = 1.17) over the alleles reported in the original GWAS (OR = 1.08). In summary, in this detailed analysis of the prostate cancer risk loci reported from GWAS, we have validated and improved upon markers of risk in some regions that better define the association with prostate cancer in African Americans. Our findings with variants at 8q24 also reinforce the importance of this region as a major risk locus for prostate cancer in men of African ancestry. PMID:21637779

Adoption, Acceptability, and Effectiveness of a Mobile Health App for Personalized Prostate Cancer Survivorship Care: Protocol for a Realist Case Study of the Ned App

PubMed Central

Cafazzo, Joseph A; Feifer, Andrew

2017-01-01

Background By 2030, prostate cancer will be the most commonly diagnosed cancer in North America. To mitigate this impending challenge, comprehensive support mechanisms for disease- and treatment-specific changes in health and well-being must be proactively designed and thoughtfully implemented for streamlined survivorship care. mHealth apps have been lauded as a promising complement to current outpatient treatment and monitoring strategies, but have not yet been widely used to support prostate cancer survivorship needs. A realist evaluation is needed to examine the impact of such apps on the prostate cancer survivorship experience. Objective We seek to gain an understanding of how an mHealth app for prostate cancer survivorship care called Ned (No Evident Disease) is adopted and accepted by patients, caregivers, and clinicians. We also aim to determine the effect of Ned on health-related quality of life, satisfaction with cancer care, unmet needs, self-efficacy, and prostate cancer-related levels of anxiety. Methods The Ned case study is a 12-month mixed-methods embedded single-case study with a nested within-group pre-post comparison of health outcomes. We will give 400 patients, 200 caregivers, and 10 clinicians access to Ned. Participants will be asked to complete study assessments at baseline, 2 months, 6 months, and 12 months. We will conduct 30 semistructured qualitative interviews with patients (n=20) and their caregivers (n=10) poststudy to gain insight into their experience with the app. Results We recruited our first survivor in October 2017 and anticipate completing this study by May 2019. Conclusions This will, to our knowledge, be the first realist case study to evaluate an app for prostate cancer survivorship care. Prostate cancer survivors are set to increase in number and longevity, heightening the need for integrated survivorship solutions to provide them with optimal and durable outcomes. The knowledge gained from this study will comprehensively inform how and why Ned works, for whom, and in what circumstances. Understanding the impact of digital health interventions such as Ned on how survivors care for themselves is critical to realizing patient-centered care. PMID:29025699

Molecular imaging of prostate cancer: translating molecular biology approaches into the clinical realm.

PubMed

Vargas, Hebert Alberto; Grimm, Jan; F Donati, Olivio; Sala, Evis; Hricak, Hedvig

2015-05-01

The epidemiology of prostate cancer has dramatically changed since the introduction of prostate-specific antigen (PSA) screening in the 1980's. Most prostate cancers today are detected at early stages of the disease and are considered 'indolent'; however, some patients' prostate cancers demonstrate a more aggressive behaviour which leads to rapid progression and death. Increasing understanding of the biology underlying the heterogeneity that characterises this disease has led to a continuously evolving role of imaging in the management of prostate cancer. Functional and metabolic imaging techniques are gaining importance as the impact on the therapeutic paradigm has shifted from structural tumour detection alone to distinguishing patients with indolent tumours that can be managed conservatively (e.g., by active surveillance) from patients with more aggressive tumours that may require definitive treatment with surgery or radiation. In this review, we discuss advanced imaging techniques that allow direct visualisation of molecular interactions relevant to prostate cancer and their potential for translation to the clinical setting in the near future. The potential use of imaging to follow molecular events during drug therapy as well as the use of imaging agents for therapeutic purposes will also be discussed. • Advanced imaging techniques allow direct visualisation of molecular interactions in prostate cancer. • MRI/PET, optical and Cerenkov imaging facilitate the translation of molecular biology. • Multiple compounds targeting PSMA expression are currently undergoing clinical translation. • Other targets (e.g., PSA, prostate-stem cell antigen, GRPR) are in development.

An object lesson: source determines the relations that trait anxiety, prostate cancer worry, and screening fear hold with prostate screening frequency.

PubMed

Consedine, Nathan S; Adjei, Brenda A; Ramirez, Paul M; McKiernan, James M

2008-07-01

Fears regarding prostate cancer and the associated screening are widespread. However, the relations between anxiety, cancer worry, and screening fear and screening behavior are complex, because anxieties stemming from different sources have different effects on behavior. In differentiating among anxieties from different sources (trait anxiety, cancer worry, and screening fear), we expected that cancer worry would be associated with more frequent screening, whereas fear of screening would be associated with less frequent screening. Hypotheses were tested in a sample of 533 men (ages 45-70 years) recruited using a stratified cluster-sampling plan. Men provided information on demographic and structural variables (age, education, income, marital status, physician discussion of risk and screening, access, and insurance) and completed a set of anxiety measures (trait anxiety, cancer worry, and screening fear). As expected, two-step multiple regressions controlling for demographics, health insurance status, physician discussion, and health-care system barriers showed that prostate-specific antigen and digital rectal examination frequencies had unique associations with cancer worry and screening fear. Specifically, whereas cancer worry was associated with more frequent screening, fear of screening was associated with less frequent screening at least for digital rectal examination; trait anxiety was inconsistently related to screening. Data are discussed in terms of their implications for male screening and the understanding of how anxiety motivates health behaviors. It is suggested that understanding the source of anxiety and the manner in which health behaviors such as cancer screenings may enhance or reduce felt anxiety is a likely key to understanding the associations between anxiety and behavioral outcomes.

Proteasome-associated deubiquitinase ubiquitin-specific protease 14 regulates prostate cancer proliferation by deubiquitinating and stabilizing androgen receptor.

PubMed

Liao, Yuning; Liu, Ningning; Hua, Xianliang; Cai, Jianyu; Xia, Xiaohong; Wang, Xuejun; Huang, Hongbiao; Liu, Jinbao

2017-02-02

Androgen receptor (AR) is frequently over-expressed and plays a critical role in the growth and progression of human prostate cancer. The therapy attempting to target AR signalling was established in decades ago but the treatment of prostate cancer is far from being satisfactory. The assignable cause is that our understanding of the mechanism of AR regulation and re-activation remains incomplete. Increasing evidence suggests that deubiquitinases are involved in the regulation of cancer development and progression but the specific underlying mechanism often is not elucidated. In the current study, we have identified ubiquitin-specific protease 14 (USP14) as a novel regulator of AR, inhibiting the degradation of AR via deubiquitinating this oncoprotein in the androgen-responsive prostate cancer cells. We found that (i) USP14 could bind to AR, and additionally, both genetic and pharmacological inhibition of USP14 accelerated the ubiquitination and degradation of AR; (ii) downregulation or inhibition of USP14 suppressed cell proliferation and colony formation of LNcap cells and, conversely, overexpression of USP14 promoted the proliferation; and (iii) reduction or inhibition of USP14 induced G0/G1 phase arrest in LNcap prostate cancer cells. Hence, we conclude that USP14 promotes prostate cancer progression likely through stabilization of AR, suggesting that USP14 could be a promising therapeutic target for prostate cancer.

Epigenetics of prostate cancer and the prospect of identification of novel drug targets by RNAi screening of epigenetic enzymes.

PubMed

Björkman, Mari; Rantala, Juha; Nees, Matthias; Kallioniemi, Olli

2010-10-01

Alterations in epigenetic processes probably underlie most human malignancies. Novel genome-wide techniques, such as chromatin immunoprecipitation and high-throughput sequencing, have become state-of-the-art methods to map the epigenomic landscape of development and disease, such as in cancers. Despite these advances, the functional significance of epigenetic enzymes in cancer progression, such as prostate cancer, remain incompletely understood. A comprehensive mapping and functional understanding of the cancer epigenome will hopefully help to facilitate development of novel cancer therapy targets and improve future diagnostics. The authors have developed a novel cell microarray-based high-content siRNA screening technique suitable to address the putative functional role and impact of all known putative and novel epigenetic enzymes in cancer, including prostate cancer.

The Complex Interplay Between Cholesterol and Prostate Malignancy

PubMed Central

Solomon, Keith R.; Freeman, Michael R.

2011-01-01

Research into the topic of the role of cholesterol and prostate disease has been ongoing for many years, however our mechanistic and translational understanding is still poor. Recent evidence indicates that cholesterol lowering drugs reduce the risk of aggressive prostate cancer, however the studies in this area, performed over many years, reflect much controversy and uncertainty. Here we explore the entire literature on the relationship between circulating cholesterol and prostate cancer, with consideration and criticism of the older as well as the newer studies. We consider why low cholesterol is associated with both increased and decreased risk of advanced prostate cancer, and explain why both observations are probably correct. We discuss the conflicting results of randomized placebo-controlled trials of statin drugs vs. observational studies and demonstrate that a predominance of pravastatin in the randomized trials paints a distorted view of statin effects. Lastly, we discuss new data suggesting that a critical aspect of the role of cholesterol in prostate cancer progression is through its role in intratumoral steroidogenesis. With these points addressed, the data strongly point to hypercholesterolemia as a risk factor for prostate cancer progression and suggest clinical opportunities for the use of cholesterol lowering therapies to alter disease course. PMID:21798387

The Role of Soy Phytoestrogens on Genetic and Epigenetic Mechanisms of Prostate Cancer.

PubMed

Karsli-Ceppioglu, Seher; Ngollo, Marjolaine; Judes, Gaëlle; Penault-LLorca, Frédérique; Bignon, Yves-Jean; Guy, Laurent; Bernard-Gallon, Dominique

2015-01-01

Soy phytoestrogens are dietary components with considerable effects on reducing the incidence of prostate cancer. Epidemiological studies demonstrated that occurrence of prostate cancer is relatively low in Asia and Southern Europe, a status associated with consuming of soy isoflavones, such as genistein, daidzein, and glycitein. Soy phytoestrogens exert their activity on molecular mechanisms, including cell-cycle control, induction of apoptosis, inhibition of angiogenesis, and metastasis. In addition, they have antioxidant activity and show regulatory effect on the expression of genes involved in DNA damage and repair. Furthermore, the epigenetic regulation of gene expression can be modified by soy phytoestrogens. They show regulatory effects on gene activity by altering DNA methylation and/or histone modification patterns. In this chapter, we discuss the role of soy phytoestrogens on the genetic and epigenetic mechanisms of prostate cancer. We attempt to provide further insight in order to understand the underlying mechanisms of protective effects of soy phytoestrogens in preventing prostate cancer. © 2015 Elsevier Inc. All rights reserved.

[Neuroendocrine prostate cancer: Natural history, molecular features, therapeutic management and future directions].

PubMed

Campedel, Luca; Kossaï, Myriam; Blanc-Durand, Paul; Rouprêt, Morgan; Seisen, Thomas; Compérat, Eva; Spano, Jean-Philippe; Malouf, Gabriel

2017-09-01

Neuroendocrine prostate cancer is a rare malignancy with a an adverse prognostic. Histologically, It can be pure (small cells or large cells neuroendocrine carcinoma) or mixed with a adenocarcinoma component. Rarely diagnosed de novo, neuroendocrine prostate cancer is generally associated with advanced stage disease resistant to castration. As such, this histological subtype could represent an aggressive evolution of prostatic adenocarcinoma, through the epithelio-neuroendocrine transdifferentiation mechanism (phenomenon of lineage plasticity). Nonetheless, neuroendocrine prostate cancer is a heterogeneous malignancy with multiple histopathological variants showing distinct clinical features. The broad variety of molecular analyses could help to understand the ontogeny of this histological subtype and its signaling pathways. This may also allow identifying diagnostic and prognostic biomarkers as well as potential molecular targets. However, treatment options are currently limited and consist only in platinium-based chemotherapy for advanced stage disease. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

GPs views and understanding of PSA testing, screening and early detection; survey.

PubMed

Sutton, J; Melia, J; Kirby, M; Graffy, J; Moss, S

2016-05-01

There is currently no national prostate cancer screening programme in the UK. However, patients 50 years and older are entitled to a prostate specific antigen (PSA) test, if informed on the advantages and disadvantages of testing and their risk of cancer. The Prostate Cancer Risk Management Programme (PCRMP) provides this guidance. The aim of this study was to access GPs' views and understanding of PSA testing, prostate cancer screening and early detection. A total of 708 questionnaires were returned by GPs across two English regions in 2013 and the GP questionnaire responses were quantitatively analysed. In the 699 completed questionnaires, the majority of GPs were well informed about PSA testing, screening and early detection. Only 32% used guidelines for referral, 14% knew all age-specific PSA referral levels, 71% that Black men have a higher prostate cancer risk than White men (22% correctly answered threefold increase) and 82% that family history is a risk factor. A further 78% thought electronic prompts during consultation would encourage PCRMP guideline usage and 75% had never been offered a PSA test and prostate cancer educational course, of which 73% would like to attend a course. Only 23% were aware of the latest PSA screening evidence and 94% would like an update. Participating GPs seem to be well informed but need more information and tools to help follow recommended guidance. In particular, increased awareness of PCRMP guidelines especially by automated methods, further educational courses and evidence updates would be beneficial. © 2016 John Wiley & Sons Ltd.

The perspective of prostate cancer patients and patients' partners on the psychological burden of androgen deprivation and the dyadic adjustment of prostate cancer couples.

PubMed

Hamilton, Lisa Dawn; Van Dam, Dexter; Wassersug, Richard J

2016-07-01

Prostate cancer and its treatments, particularly androgen deprivation therapy (ADT), affect both patients and partners. This study assessed how prostate cancer treatment type, patient mood, and sexual function related to dyadic adjustment from patient and partner perspectives. Men with prostate cancer (n = 206) and partners of men with prostate cancer (n = 66) completed an online survey assessing the patients' mood (profile of mood states short form), their dyadic adjustment (dyadic adjustment scale), and sexual function (expanded prostate cancer index composite). Analyses of covariance found that men on ADT reported better dyadic adjustment compared with men not on ADT. Erectile dysfunction was high for all patients, but a multivariate analysis of variance found that those on ADT experienced greater bother at loss of sexual function than patients not on ADT, suggesting that loss of libido when on ADT does not mitigate the psychological distress associated with loss of erections. In a multiple linear regression, patients' mood predicted their dyadic adjustment, such that worse mood was related to worse dyadic adjustment. However, more bother with patients' overall sexual function predicted lower relationship scores for the patients, while the patients' lack of sexual desire predicted lower dyadic adjustment for partners. Both patients and partners are impacted by the prostate cancer treatment effects on patients' psychological and sexual function. Our data help clarify the way that prostate cancer treatments can affect relationships and that loss of libido on ADT does not attenuate distress about erectile dysfunction. Understanding these changes may help patients and partners maintain a co-supportive relationship. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Replication of prostate cancer risk loci in a Japanese case-control association study.

PubMed

Yamada, Hiroki; Penney, Kathryn L; Takahashi, Hiroyuki; Katoh, Takahiko; Yamano, Yuko; Yamakado, Minoru; Kimura, Takahiro; Kuruma, Hidetoshi; Kamata, Yuko; Egawa, Shin; Freedman, Matthew L

2009-10-07

Two prostate cancer genome-wide scans in populations of European ancestry identified several genetic variants that are strongly associated with prostate cancer risk. The effect of these risk variants and their cumulative effect in other populations are unknown. We evaluated the association of 23 risk single-nucleotide polymorphisms (SNPs) with prostate cancer risk and clinical covariates (Gleason score, tumor aggressiveness, and age at diagnosis) in men of Japanese ancestry (311 case subjects and 1035 control subjects) using unconditional logistic regression. We also used logistic regression to test the association between increasing numbers of independently associated risk alleles and the risk of prostate cancer, prostate cancer aggressiveness, and age at diagnosis. All statistical tests were two-sided. Seven of the 23 SNPs (five independent loci) were associated with prostate cancer risk (P values ranged from .0084 to 2.3 x 10(-8) and effect sizes [estimated as odds ratios, ORs] ranged from 1.35 to 1.82). None of the seven SNPs was associated with Gleason score or aggressive disease. rs6983561 and rs4430796 were associated with age at diagnosis (Ps = .0188 and .0339, respectively). Men with six or more risk alleles (27% of case patients and 11% of control subjects) had a higher risk of prostate cancer than men with two or fewer risk alleles (7% of case patients and 20% of control subjects) (OR = 6.22, P = 1.5 x 10(-12)). These results highlight the critical importance of considering ancestry in understanding how risk alleles influence disease and suggest that risk estimates and variants differ across populations. It is important to perform studies in multiple ancestral populations so that the composite genetic architecture of prostate cancer can be rigorously addressed.

Lack of Comprehension of Common Prostate Cancer Terms in an Underserved Population

PubMed Central

Kilbridge, Kerry L.; Fraser, Gertrude; Krahn, Murray; Nelson, Elizabeth M.; Conaway, Mark; Bashore, Randall; Wolf, Andrew; Barry, Michael J.; Gong, Debra A.; Nease, Robert F.; Connors, Alfred F.

2009-01-01

Purpose To assess the comprehension of common medical terms used in prostate cancer in patient education materials to obtain informed consent, and to measure outcomes after prostate cancer treatment. We address this issue among underserved, African-American men because of the increased cancer incidence and mortality observed in this population. Patients and Methods We reviewed patient education materials and prostate-specific quality-of-life instruments to identify technical terms describing sexual, urinary, and bowel function. Understanding of these terms was assessed in face-to-face interviews of 105, mostly African-American men, age ≥ 40, from two low-income clinics. Comprehension was evaluated using semiqualitative methods coded by two independent investigators. Demographics were collected and literacy was measured. Results Fewer than 50% of patients understood the terms “erection” or “impotent.” Only 5% of patients understood the term “incontinence” and 25% understood the term “bowel habits.” More patients recognized word roots than related terms or compound words (eg, “rectum” v “rectal urgency,” “intercourse” v “vaginal intercourse”). Comprehension of terms from all domains was statistically significantly correlated with reading level (P < .001). Median literacy level was fourth to sixth grade. Prostate cancer knowledge was poor. Many patients had difficulty locating key anatomic structures. Conclusion Limited comprehension of prostate cancer terms and low literacy create barriers to obtaining informed consent for treatment and to measuring prostate cancer outcomes accurately in our study population. In addition, the level of prostate cancer knowledge was poor. These results highlight the need for prostate cancer education efforts and outcomes measurements that consider literacy and use nonmedical language. PMID:19307512

An RBF-PSO based approach for modeling prostate cancer

NASA Astrophysics Data System (ADS)

Perracchione, Emma; Stura, Ilaria

2016-06-01

Prostate cancer is one of the most common cancers in men; it grows slowly and it could be diagnosed in an early stage by dosing the Prostate Specific Antigen (PSA). However, a relapse after the primary therapy could arise in 25 - 30% of cases and different growth characteristics of the new tumor are observed. In order to get a better understanding of the phenomenon, a two parameters growth model is considered. To estimate the parameters values identifying the disease risk level a novel approach, based on combining Particle Swarm Optimization (PSO) with meshfree interpolation methods, is proposed.

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.

Readability of American online patient education materials in urologic oncology: a need for simple communication.

PubMed

Pruthi, Amanda; Nielsen, Matthew E; Raynor, Mathew C; Woods, Michael E; Wallen, Eric M; Smith, Angela B

2015-02-01

To determine the readability levels of reputable cancer and urologic Web sites addressing bladder, prostate, kidney, and testicular cancers. Online patient education materials (PEMs) for bladder, prostate, kidney, and testicular malignancies were evaluated from the American Cancer Society, American Society of Clinical Oncology, National Cancer Institute, Urology Care Foundation, Bladder Cancer Advocacy Network, Prostate Cancer Foundation, Kidney Cancer Association, and Testicular Cancer Resource Center. Grade level was determined using several readability indices, and analyses were performed on the basis of cancer type, Web site, and content area (general, causes, risk factors and prevention, diagnosis and staging, treatment, and post-treatment). Estimated grade level of online PEMs ranged from 9.2 to 14.2 with an overall mean of 11.7. Web sites for kidney cancer had the least difficult readability (11.3) and prostate cancer had the most difficult readability (12.1). Among specific Web sites, the most difficult readability levels were noted for the Urology Care Foundation Web site for bladder and prostate cancer and the Kidney Cancer Association and Testicular Cancer Resource Center for kidney and testes cancer. Readability levels within content areas varied on the basis of the disease and Web site. Online PEMs in urologic oncology are written at a level above the average American reader. Simplification of these resources is necessary to improve patient understanding of urologic malignancy. Copyright © 2015 Elsevier Inc. All rights reserved.

Sex steroid hormone metabolism in relation to risk of aggressive prostate cancer

PubMed Central

Black, Amanda; Pinsky, Paul F.; Grubb, Robert L.; Falk, Roni T.; Hsing, Ann W.; Chu, Lisa; Meyer, Tamra; Veenstra, Timothy D.; Xu, Xia; Yu, Kai; Ziegler, Regina G.; Brinton, Louise A.; Hoover, Robert N.; Cook, Michael B.

2014-01-01

Background The combined action of androgens and estrogens—specifically their balance—may play a role in prostate carcinogenesis but existing evidence is sparse and inconsistent. We investigated associations between serum sex steroid hormones, including estrogen metabolites, and risk of aggressive prostate cancer. Methods In a case-control study nested within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial cohort we measured serum estrone, estradiol and 13 estrogen metabolites, in the 2-, 4, or 16-hydroxylation pathways, using a liquid chromatography-tandem mass spectrometry assay. Cases (n=195) were non-Hispanic white men aged 55–70 years when diagnosed with aggressive prostate cancer (stage III or IV and/or Gleason ≥7). Controls (n=195) were non-Hispanic white men without prostate cancer who were frequency-matched to cases by age and year at blood draw, time since baseline screen. Only men with serum testosterone and sex hormone-binding globulin measured previously were eligible. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (95%CI). Results Risk of aggressive prostate cancer was strongly inversely associated with estradiol:testosterone ratio (OR4th quartile vs. 1st =0.27, 95% CI 0.12–0.59, p trend=0.003) and positively associated with 2:16α-hydroxyestrone ratio (OR4th quartile vs. 1st =2.44, 95% CI 1.34–4.45, p trend=0.001). Estradiol, estrone and estrogen metabolites were unrelated to risk. Conclusions Our findings suggest that sex steroid hormones, specifically the estrogen-androgen balance, may be important in the development of aggressive prostate cancer. Impact Improved understanding of the hormonal etiology of prostate cancer is critical for prevention and therapeutic interventions. PMID:25178985

microRNA-218 inhibits prostate cancer cell growth and promotes apoptosis by repressing TPD52 expression

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

Han, Guangye, E-mail: guangyehan@126.com; Fan, Maochuan, E-mail: maochunfan@outlook.com; Zhang, Xinjun, E-mail: xinjunzhang11@163.com

2015-01-16

Highlights: • miR-218 expression is downregulated in prostate cancer. • miR-218 inhibits prostate tumor cells proliferation partially through promoting apoptosis. • miR-218 targets TPD52 by binding to its 3′-UTR. • miR-218 suppresses prostate cancer cell growth through inhibiting TPD52 expression. - Abstract: The tumor protein D52 (TPD52) is an oncogene overexpressed in prostate cancer (PC) due to gene amplification. Although the oncogenic effect of TPD52 is well recognized, how its expression is regulated is still not clear. This study tried to explore the regulative role of miR-218, a tumor suppressing miRNA on TPD52 expression and prostate cancer cell proliferation. Wemore » found the expression of miR-218 was significantly lower in PC specimens. Based on gain and loss of function analysis, we found miR-218 significantly inhibit cancer cell proliferation by inducing apoptosis. These results strongly suggest that miR-218 plays a tumor suppressor role in PC cells. In addition, our data firstly demonstrated that miR-218 directly regulates oncogenic TPD52 in PC3 cells and the miR-218-TPD52 axis can regulate growth of this prostate cancer cell line. Knockdown of TPD52 resulted in significantly increased cancer cell apoptosis. Clearly understanding of oncogenic TPD52 pathways regulated by miR-218 might be helpful to reveal new therapeutic targets for PC.« less

Molecular insight into the differential anti-androgenic activity of resveratrol and its natural analogs: In Silico approach to understand biological actions

USDA-ARS?s Scientific Manuscript database

The androgen receptor (AR) is a therapeutic target for the treatment of prostate cancer. Androgen receptor reactivation during the androgen-independent stage of prostate cancer is mediated by numerous mechanisms including expression of AR mutants and splice variants that become non-responsive to con...

Bone Morphogenetic Proteins, Antagonists and Receptors in Prostate Cancer

DTIC Science & Technology

2005-01-01

expressed in prostate. This work investigates BMP receptors and BMP antagonists to understand the basic mechanisms to inhibit the BMP signaling in...during embryoge- nesis, and prostate cancer metastases to bone. BMP functions can be inhibited by antagonists such as Noggin or DAN. DAN is a protein...protein along with a constant 0-6 -1 10 100 1000 1O0ng/ml of BMP-6, we were able to show a ng/ml BMP-6 dose-dependent inhibition of BMP-6 activity in DU

Targeting the androgen receptor pathway in castration-resistant prostate cancer: progresses and prospects

PubMed Central

Ferraldeschi, R; Welti, J; Luo, J; Attard, G; de Bono, JS

2015-01-01

Androgen receptor (AR) signaling is a critical pathway for prostate cancer cells, and androgen-deprivation therapy (ADT) remains the principal treatment for patients with locally advanced and metastatic disease. However, over time, most tumors become resistant to ADT. The view of castration-resistant prostate cancer (CRPC) has changed dramatically in the last several years. Progress in understanding the disease biology and mechanisms of castration resistance led to significant advancements and to paradigm shift in the treatment. Accumulating evidence showed that prostate cancers develop adaptive mechanisms for maintaining AR signaling to allow for survival and further evolution. The aim of this review is to summarize molecular mechanisms of castration resistance and provide an update in the development of novel agents and strategies to more effectively target the AR signaling pathway. PMID:24837363

Development and Evaluation of a Tumor Marker for Prostate Cancer — EDRN Public Portal

Cancer.gov

Major strides in the early detection, staging, monitoring, and risk stratification of men with prostate cancer have been realized over the last few decades. We have recently witnessed a reduction in the death rate for prostate cancer, stage migration with increased numbers of men with local/regional disease, and a greater understanding of the natural history of progression following recurrence. These advances, while not solely dependant on biomarkers, can be attributed to the discovery of Prostate Specific Antigen (PSA) in the late 1970's. In the wake of these discoveries, we still continue to unnecessarily biopsy men at risk for having prostate cancer to identify the 1:4 with the disease, understage men with presumed local disease, continue to lack an accurate method for staging which can direct treatment options for the individual patient and continue to poorly understand the tumor biology and kinetics of disease progression. Clearly, discovery of a new tumor marker and validation/clinical investigation of the markers are mandatory to advance our knowledge and direct the care of men with prostate cancer. With this research, we intend to evaluate the clinical, diagnostic, and prognostic accuracy of new and existing biomarkers on a prospective serum bank collected from men either participating in early detection programs or engaging in pre or post treatment situations. By increasing our clinical research and specimen collections we hope to further advance the staging and direction for treatment in men with prostate cancer. This study approaches patients scheduled for a prostate biopsy, patients visiting the Urology Outpatient Clinic with PSA elevation, patients scheduled for radical prostatectomy, prostate cancer patients with scheduled appointments in Radiation Oncology and men participating in early prostate cancer detection screenings. Subjects will be excluded from the study if: 1) Subjects have any mental impairment that would hinder the ability to provide informed consent. 2) The subject has undergone a radical prostatectomy and is visiting the urology clinic for a follow up appointment. We can not evaluate the protein profiles in the serum/urine for this group of patients because of prostate removal. 3) Subjects have had previous chemotherapy treatment. Such treatments often induce oxidative damage that could affect protein expression. Therefore, such patients are excluded as their exposure histories may be confounded with respect to exposures relevant to prostate cancer. 4) The patient has had previous prostate surgery. These procedures will affect protein expression. 5) Subjects have had previous cancer other than non-melanoma skin cancer. Systemic oxidative DNA damage is suspected as a potential etiologic factor in a number of other cancers. Therefore, such patients are excluded as their exposure histories maybe confounded with respect to exposures relevant to prostate cancer. Upon receiving consent, urine and blood specimens are collected from the subjects. The urine and blood are then processed and stored in our freezer bank. This study represents little to no risk to the patient. Risks include mild pain and bruising which may result from the needle stick. There is a very small chance of infection. There is also a very small chance that the patient may feel faint or pass out from the needle stick. These are the usual risks associated with phlebotomy. Collection of the urine introduces no increased risk to the patient. Adverse experiences that are both serious and unexpected will be immediately reported by telephone to the Primary Investigator, Alan. W. Partin M.D., Ph.D., (410) 614-4876.

Evaluating long-term patient-centered outcomes following prostate cancer treatment: findings from the Michigan Prostate Cancer Survivor study.

PubMed

Darwish-Yassine, May; Berenji, Manijeh; Wing, Diane; Copeland, Glenn; Demers, Raymond Y; Garlinghouse, Carol; Fagerlin, Angela; Newth, Gail E; Northouse, Laurel; Holmes-Rovner, Margaret; Rovner, David; Sims, Jerry; Wei, John T

2014-03-01

Advances in screening and treatment of prostate cancer have dramatically increased the number of survivors in the US population. Yet the effect of screening is controversial, and in some instances may not be beneficial. Previous studies have typically only reported outcomes of treatment and symptoms within a short time frame following treatment. The persistence of such symptoms over time necessitates an improvement of survivor care so that the medical and support needs of these patients are met. This study aims to perform a patient-centered survey of prostate cancer survivors in the Michigan Cancer Registry to identify treatment side effect rates, evaluate survivors' access to preventive care services post-prostate cancer treatment, and assess the informational needs of these survivors regarding their prostate cancer. Linking case files of the Michigan Cancer Registry with records from the National Death Index, we identified prostate cancer patients diagnosed between 1985 and 2004 and alive on 31 December 2005. Participants were selected using a stratified cross-sectional sampling strategy to ensure adequate inclusion of survivors based upon race and ethnicity, urban versus rural location, and number of years since diagnosis of prostate cancer. A total of 2,499 surveys were completed and returned. (1) Physical symptoms--assessing bowel, sexual, urinary, and vitality symptoms by treatment modality. (2) Access to care--identifying whether diagnostic tests for prostate cancer (prostate-specific antigen (PSA) and digital rectal examination) were performed. Determining whether the survivors had knowledge of the "watchful waiting" paradigm for prostate cancer surveillance. (3) Informational needs--assessing whether the informational needs of patients were addressed by providers. Evaluating the significant predictors associated with seeking information about prostate cancer from any other source. Identifying what factors influenced a person to actively seek out information and what factors guide which primary information source a survivor would use. Median duration between prostate cancer diagnosis and survey response was 9 years. Of the study population, 80 % was diagnosed at an early stage. Survivors had reported significant problems in the 4 weeks prior to survey. Of the survivors, 88.1 % reported having a PSA test since diagnosis of prostate cancer, with 93 % of them having it done at least once per year. Of the survivors, 82.6 % reported that a healthcare provider gave them information on prostate cancer. Of this 82.6 %, 86.4 % had this information provided by a urologist, 45.4 % by a primary care physician, and 29.2 % by an oncologist. The primary source of information for these survivors was "healthcare provider" (59.2 %). Persistent symptoms subsequent to prostate cancer treatment suggest a gap in symptom management. Future research should support long-term studies of active surveillance versus active treatment outcomes to understand the feasibility of minimizing the burden of long-term physical symptoms arising from prostate cancer treatment. Clinicians must assess post-treatment distress long after treatment has ended to identify when supportive care is needed. More informational resources should be allocated to prostate cancer survivors to ensure that they are well-educated about their prognosis. This study is needed to ensure that the post-treatment symptoms of prostate cancer survivors are properly addressed and managed by healthcare providers over the long term.

Alternative RNA splicing of the MEAF6 gene facilitates neuroendocrine prostate cancer progression.

PubMed

Lee, Ahn R; Li, Yinan; Xie, Ning; Gleave, Martin E; Cox, Michael E; Collins, Colin C; Dong, Xuesen

2017-04-25

Although potent androgen receptor pathway inhibitors (ARPI) improve overall survival of metastatic prostate cancer patients, treatment-induced neuroendocrine prostate cancer (t-NEPC) as a consequence of the selection pressures of ARPI is becoming a more common clinical issue. Improved understanding of the molecular biology of t-NEPC is essential for the development of new effective management approaches for t-NEPC. In this study, we identify a splice variant of the MYST/Esa1-associated factor 6 (MEAF6) gene, MEAF6-1, that is highly expressed in both t-NEPC tumor biopsies and neuroendocrine cell lines of prostate and lung cancers. We show that MEAF6-1 splicing is stimulated by neuronal RNA splicing factor SRRM4. Rather than inducing neuroendocrine trans-differentiation of cells in prostate adenocarcinoma, MEAF6-1 upregulation stimulates cell proliferation, anchorage-independent cell growth, invasion and xenograft tumor growth. Gene microarray identifies that these MEAF6-1 actions are in part mediated by the ID1 and ID3 genes. These findings suggest that the MEAF6-1 variant does not induce neuroendocrine differentiation of prostate cancer cells, but rather facilitates t-NEPC progression by increasing the proliferation rate of cells that have acquired neuroendocrine phenotypes.

Trends in initial management of prostate cancer in New Hampshire.

PubMed

Ingimarsson, Johann P; Celaya, Maria O; Laviolette, Michael; Rees, Judy R; Hyams, Elias S

2015-06-01

Prostate cancer management strategies are evolving with increased understanding of the disease. Specifically, there is emerging evidence that "low-risk" cancer is best treated with observation, while localized "high-risk" cancer requires aggressive curative therapy. In this study, we evaluated trends in management of prostate cancer in New Hampshire to determine adherence to evidence-based practice. From the New Hampshire State Cancer Registry, cases of clinically localized prostate cancer diagnosed in 2004-2011 were identified and classified according to D'Amico criteria. Initial treatment modality was recorded as surgery, radiation therapy, expectant management, or hormone therapy. Temporal trends were assessed by Chi-square for trend. Of 6,203 clinically localized prostate cancers meeting inclusion criteria, 34, 30, and 28% were low-, intermediate-, and high-risk disease, respectively. For low-risk disease, use of expectant management (17-42%, p < 0.001) and surgery (29-39%, p < 0.001) increased, while use of radiation therapy decreased (49-19 %, p < 0.001). For intermediate-risk disease, use of surgery increased (24-50%, p < 0.001), while radiation decreased (58-34%, p < 0.001). Hormonal therapy alone was rarely used for low- and intermediate-risk disease. For high-risk patients, surgery increased (38-47%, p = 0.003) and radiation decreased (41-38%, p = 0.026), while hormonal therapy and expectant management remained stable. There are encouraging trends in the management of clinically localized prostate cancer in New Hampshire, including less aggressive treatment of low-risk cancer and increasing surgical treatment of high-risk disease.

Glutathione S-transferase Pi mediates proliferation of androgen-independent prostate cancer cells

PubMed Central

Hokaiwado, Naomi; Takeshita, Fumitaka; Naiki-Ito, Aya; Asamoto, Makoto; Ochiya, Takahiro; Shirai, Tomoyuki

2008-01-01

Prostate cancers generally acquire an androgen-independent growth capacity with progression, resulting in resistance to antiandrogen therapy. Therefore, identification of the genes regulated through this process may be important for understanding the mechanisms of prostate carcinogenesis. We here utilized androgen-dependent/independent transplantable tumors, newly established with the ‘transgenic rat adenocarcinoma in prostate’ (TRAP) model, to analyze their gene expression using microarrays. Among the overexpressed genes in androgen-independent prostate cancers compared with the androgen-dependent tumors, glutathione S-transferase pi (GST-pi) was included. In line with this, human prostate cancer cell lines PC3 and DU145 (androgen independent) had higher expression of GST-pi compared with LNCaP (androgen dependent) as determined by semiquantitative reverse transcription–polymerase chain reaction analysis. To investigate the roles of GST-pi expression in androgen-independent human prostate cancers, GST-pi was knocked down by a small interfering RNA (siRNA), resulting in significant decrease of the proliferation rate in the androgen-independent PC3 cell line. In vivo, administration of GST-pi siRNA–atelocollagen complex decreased GST-pi protein expression, resulting in enhanced numbers of TdT mediated dUTP-biotin nick-end labering (TUNEL)-positive apoptotic cells. These findings suggest that GST-pi might play important roles in proliferation of androgen-independent human prostate cancer cells. PMID:18413363

Barriers to prostate cancer prevention and community recommended health education strategies in an urban African American community in Jackson, Mississippi.

PubMed

Ekúndayò, Olúgbémiga T; Tataw, David B

2013-01-01

This article describes the use of survey research in collaboration with the African American urban community of Georgetown, Jackson, Mississippi to identify and understand prostate cancer knowledge, resource utilization, and health education strategies considered most effective in reaching the community with prostate cancer prevention messages. The study revealed profound needs in disease identification and resources awareness and utilization. Barriers to utilization were identified by participants to include lack of self-efficacy, low self-esteem, lack of trust in the health care system, limited knowledge of prostate pathology, and limited ability to pay. Participants' recommended strategies for reaching the community with prostate cancer education include traditional and nontraditional strategies. The list of recommendations exclude modern-day outlets such as handheld devices, Twitter, Facebook, blogs, wikis, and other Internet-based outlets. The findings provide a road map for program development and an intervention research agenda custom-tailored to the Georgetown community of Jackson, Mississippi.

New advances in focal therapy for early stage prostate cancer.

PubMed

Tay, Kae Jack; Schulman, Ariel A; Sze, Christina; Tsivian, Efrat; Polascik, Thomas J

2017-08-01

Prostate focal therapy offers men the opportunity to achieve oncological control while preserving sexual and urinary function. The prerequisites for successful focal therapy are to accurately identify, localize and completely ablate the clinically significant cancer(s) within the prostate. We aim to evaluate the evidence for current and upcoming technologies that could shape the future of prostate cancer focal therapy in the next five years. Areas covered: Current literature on advances in patient selection using imaging, biopsy and biomarkers, ablation techniques and adjuvant treatments for focal therapy are summarized. A literature search of major databases was performed using the search terms 'focal therapy', 'focal ablation', 'partial ablation', 'targeted ablation', 'image guided therapy' and 'prostate cancer'. Expert commentary: Advanced radiological tools such as multiparametric magnetic resonance imaging (mpMRI), multiparametric ultrasound (mpUS), prostate-specific-membrane-antigen positron emission tomography (PSMA-PET) represent a revolution in the ability to understand cancer function and biology. Advances in ablative technologies now provide a menu of modalities that can be rationalized based on lesion location, size and perhaps in the near future, pre-determined resistance to therapy. However, these need to be carefully studied to establish their safety and efficacy parameters. Adjuvant strategies to enhance focal ablation are under development.

Tectonic-1 contributes to the growth and migration of prostate cancer cells in vitro

PubMed Central

WANG, ZHIJUN; GAO, YI; LIU, YUSHAN; CHEN, JIE; WANG, JUNKAI; GAN, SISHUN; XU, DANFENG; CUI, XINGANG

2015-01-01

Tectonic-1 (TCTN1) is an upstream gene involved in embryonic development. The aim of the present study was to investigate the effect of the TCTN1 gene on the viability and migration of prostate cancer cells. Lentivirus-mediated short hairpin RNA (shRNA) was constructed to silence the expression of TCTN1 in PC-3 and DU145 prostate cancer cells. Cell viability and proliferation were measured using MTT and colony formation assays, and the distribution of cells in phases of the cell cycle was determined using flow cytometry. Cell migration was detected using a Transwell assay. The results demonstrated that TCTN1 was widely expressed in several human prostate cancer cell lines. Knockdown of the TCTN1 gene by RNA interference markedly suppressed cell viability and colony formation in the PC-3 and DU145 cell lines. Cell cycle progression was also arrested by TCTN1 silencing. In addition, knockdown of the TCTN1 gene led to the inhibition of cell migration in the two cell lines. These findings confirmed the direct association between the TCTN1 gene and prostate cancer growth in vitro. With further understanding and clinical investigation, this indicates the potential for future development of a novel marker for early detection and gene therapy for prostate cancer. PMID:26310786

Three-dimensional co-culture models to study prostate cancer growth, progression, and metastasis to bone.

PubMed

Wang, Ruoxiang; Xu, Jianchun; Juliette, Lisa; Castilleja, Agapito; Love, John; Sung, Shian-Ying; Zhau, Haiyen E; Goodwin, Thomas J; Chung, Leland W K

2005-10-01

Cancer-stromal interaction results in the co-evolution of both the cancer cells and the surrounding host stromal cells. As a consequence of this interaction, cancer cells acquire increased malignant potential and stromal cells become more inductive. In this review we suggest that cancer-stromal interaction can best be investigated by three-dimensional (3D) co-culture models with the results validated by clinical specimens. We showed that 3D culture promoted bone formation in vitro, and explored for the first time, with the help of the astronauts of the Space Shuttle Columbia, the co-culture of human prostate cancer and bone cells to further understand the interactions between these cells. Continued exploration of cancer growth under 3D conditions will rapidly lead to new discoveries and ultimately to improvements in the treatment of men with hormonal refractory prostate cancer.

Design and preliminary recruitment results of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP).

PubMed

Turner, E L; Metcalfe, C; Donovan, J L; Noble, S; Sterne, J A C; Lane, J A; Avery, K N; Down, L; Walsh, E; Davis, M; Ben-Shlomo, Y; Oliver, S E; Evans, S; Brindle, P; Williams, N J; Hughes, L J; Hill, E M; Davies, C; Ng, S Y; Neal, D E; Hamdy, F C; Martin, R M

2014-06-10

Screening for prostate cancer continues to generate controversy because of concerns about over-diagnosis and unnecessary treatment. We describe the rationale, design and recruitment of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP) trial, a UK-wide cluster randomised controlled trial investigating the effectiveness and cost-effectiveness of prostate-specific antigen (PSA) testing. Seven hundred and eighty-five general practitioner (GP) practices in England and Wales were randomised to a population-based PSA testing or standard care and then approached for consent to participate. In the intervention arm, men aged 50-69 years were invited to undergo PSA testing, and those diagnosed with localised prostate cancer were invited into a treatment trial. Control arm practices undertook standard UK management. All men were flagged with the Health and Social Care Information Centre for deaths and cancer registrations. The primary outcome is prostate cancer mortality at a median 10-year-follow-up. Among randomised practices, 271 (68%) in the intervention arm (198,114 men) and 302 (78%) in the control arm (221,929 men) consented to participate, meeting pre-specified power requirements. There was little evidence of differences between trial arms in measured baseline characteristics of the consenting GP practices (or men within those practices). The CAP trial successfully met its recruitment targets and will make an important contribution to international understanding of PSA-based prostate cancer screening.

Purple corn color inhibition of prostate carcinogenesis by targeting cell growth pathways.

PubMed

Long, Ne; Suzuki, Shugo; Sato, Shinya; Naiki-Ito, Aya; Sakatani, Keisuke; Shirai, Tomoyuki; Takahashi, Satoru

2013-03-01

Purple corn color is a widely used food colorant that was reported to have attenuating effects on hypertension, diabetes, and to have anti-cancer effects on colon and breast cancer. Our study is the first on its possible chemoprevention effects against prostate cancer. For this purpose an androgen-dependent prostate cancer cell line, LNCaP, was used to examine effects in vitro. Purple corn color inhibited the proliferation of LNCaP cells by decreasing the expression of Cyclin D1 and inhibiting the G1 stage of the cell cycle. Thirty-six male transgenic rats for adenocarcinoma of prostate were fed basic diet or diet with purple corn color for 8 weeks. Purple corn color decreased the incidence of adenocarcinoma in the lateral prostate and slowed down the progression of prostate cancer. A lower Ki67 positive rate, a decrease of the expression of Cyclin D1, and downregulation of the activation of Erk1/2 and p38 MAPK were observed in the group consuming purple corn color in the diet. Since purple corn color is a mixture, determining its active component should help in the understanding and usage of purple corn color for prostate cancer chemoprevention. Therefore, the three major anthocyanins in purple corn color, cyanidin-3-glucoside, pelargonidin-3-glucoside and peonidin-3-glucoside, were tested with LNCaP cells. The results suggested that cyanidin-3-glucoside and pelargonidin-3-glucoside are the active compounds. © 2012 Japanese Cancer Association.

Targeting the relaxin hormonal pathway in prostate cancer.

PubMed

Neschadim, Anton; Summerlee, Alastair J S; Silvertown, Joshua D

2015-11-15

Targeting the androgen signalling pathway has long been the hallmark of anti-hormonal therapy for prostate cancer. However, development of androgen-independent prostate cancer is an inevitable outcome to therapies targeting this pathway, in part, owing to the shift from cancer dependence on androgen signalling for growth in favor of augmentation of other cellular pathways that provide proliferation-, survival- and angiogenesis-promoting signals. This review focuses on the role of the hormone relaxin in the development and progression of prostate cancer, prior to and after the onset of androgen independence, as well as its role in cancers of other reproductive tissues. As the body of literature expands, examining relaxin expression in cancerous tissues and its role in a growing number of in vitro and in vivo cancer models, our understanding of the important involvement of this hormone in cancer biology is becoming clearer. Specifically, the pleiotropic functions of relaxin affecting cell growth, angiogenesis, blood flow, cell migration and extracellular matrix remodeling are examined in the context of cancer progression. The interactions and intercepts of the intracellular signalling pathways of relaxin with the androgen pathway are explored in the context of progression of castration-resistant and androgen-independent prostate cancers. We provide an overview of current anti-hormonal therapeutic treatment options for prostate cancer and delve into therapeutic approaches and development of agents aimed at specifically antagonizing relaxin signalling to curb tumor growth. We also discuss the rationale and challenges utilizing such agents as novel anti-hormonals in the clinic, and their potential to supplement current therapeutic modalities. © 2014 UICC.

Progesterone receptor in the prostate: A potential suppressor for benign prostatic hyperplasia and prostate cancer.

PubMed

Chen, RuiQi; Yu, Yue; Dong, Xuesen

2017-02-01

Advanced prostate cancer undergoing androgen receptor pathway inhibition (ARPI) eventually progresses to castrate-resistant prostate cancer (CRPC), suggesting that (i) androgen receptor (AR) blockage is incomplete, and (ii) there are other critical molecular pathways contributing to prostate cancer (PCa) progression. Although most PCa occurs in the epithelium, prostate stroma is increasingly believed to play a crucial role in promoting tumorigenesis and facilitating tumor progression. In the stroma, sex steroid hormone receptors such as AR and estrogen receptor-α are implicated to have important functions, whereas the progesterone receptor (PR) remains largely under-investigated despite the high sequence and structural similarities between PR and AR. Stromal progesterone/PR signaling may play a critical role in PCa development and progression because not only progesterone is a critical precursor for de novo androgen steroidogenesis and an activator of mutant androgen receptors, but also PR functions in a ligand-independent manner in various important pathways. In fact, recent progress in our understanding of stromal PR function suggests that this receptor may exert an inhibitory effect on benign prostatic hyperplasia (BPH), reactive stroma development, and PCa progression. These early findings of stromal PR warrant further investigations as this receptor could be a potential biomarker and therapeutic target in PCa management. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

African and Afro-Caribbean men's experiences of prostate cancer.

PubMed

Anderson, Beverley; Marshall-Lucette, Sylvie

It is well documented that prostate cancer presents a significant health problem for middle-aged and elderly men in the UK, with further evidence suggesting that the disease is more prevalent in men of African and Afro-Caribbean (AAC) ethnicity. There is also evidence that these men are diagnosed much later and that the disease is more aggressive than in Caucasian men. To explore AAC men's experiences of prostate cancer and their understanding of its associated risks. The purpose was to gain an insight from these men's perspectives and ascertain whether a more focused health promotion strategy, and specific UK-based research, was needed in this area. A purposive sample of seven AAC men was recruited from a hospital trust's patient list after gaining approval from a research ethics committee. In-depth face-to-face interviews were carried out and the transcripts analysed thematically. The four main themes that emerged were: disease-prompted awareness, checking up as a necessary evil, defining and constructing factors influencing prostate cancer screening uptake, and appraising perceived myths about prostate cancer through personal beliefs. Among this group of AAC men, socioeconomic status, such as education and professional background, were factors that influenced their level of awareness of prostate cancer and prompted their decisions to seek help. However, it is evident from these men's perspectives that a more specific health education strategy that promotes early detection and management, targeting AAC men, would help in demystifying prostate cancer and encourage them to seek help earlier. Further research studies and health education in prominent social outlets are recommended in increasing AAC men's awareness of prostate cancer and its associated risks.

Patient and disease factors affecting the choice and adherence to active surveillance.

PubMed

Dall'Era, Marc A

2015-05-01

Treatment decisions for low-risk prostate cancer are arguably some of the most challenging in oncology. Active surveillance has emerged as an important option for many men with tumors estimated to have a low metastatic potential. Multiple complex patient and physician factors affect the recommendation, selection, and adherence to active surveillance. While baseline clinical criteria are used to identify candidates for this approach, it is important to identify and understand other forces that may influence the management of prostate cancer with active surveillance. Patient perceptions and acceptance of active surveillance have improved over time. Treatment decisions for prostate cancer are strongly associated with physician recommendations, and a high-quality relationship between the patient and his healthcare system is critical to successful active surveillance. Patient understanding of prostate cancer and consistency of information received from separate physicians can affect a decision to pursue active surveillance. Psychological symptoms, most notably regarding anxiety and distress, can affect adherence to active surveillance over time. In general, anxiety for men on active surveillance is low, and lifestyle interventions and self-management strategies may be helpful for increasing quality of life and limiting abandonment of active surveillance in the absence of disease progression. Multiple factors may affect the decision for and adherence to active surveillance for prostate cancer. It is important for both physicians and patients to be aware of these issues and work towards individualized approaches and interventions as needed to increase adoption of active surveillance in the future.

Cancer Prevention in the Precision Medicine Era

Cancer.gov

Dr. Rebbeck’s research focuses on the etiology and prevention of cancer, with an emphasis on cancers with a genetic etiology and those that are associated with disparities in incidence or mortality by race. He has directed multiple large molecular epidemiologic studies and international consortia that have been used to identify and characterize genes involved in cancer etiology, understand the relationship of allelic variation with biochemical or physiological traits, explore interactions of inherited and somatic genomic variation with epidemiological risk factors. His research also focuses on the roles of biological and social factors on prostate cancer disparities and prostate cancer in Africa through the Men of African Descent and Carcinoma of the Prostate (MADCaP) consortium. He has also led a number of consortia that study carriers of BRCA1 or BRCA2 mutations to understand breast, ovarian, and prostate cancer risk and precision prevention interventions that may reduce that risk. In addition to his research activities, Dr. Rebbeck leads a number of initiatives on the Harvard Campus. He serves as Associate Director for Equity and Engagement in the Dana-Farber / Harvard Cancer Center and Co-Director for the Collective Impact Program of Harvard Catalyst. In this role, he prioritizes the cancer research agenda to maximize disease prevention and risk reduction in Massachusetts. He also oversees a team charged with ensuring that this research engages with and positively impacts communities with the greatest disease burden.  As Director of Global Oncology at the Dana Farber Cancer Institute, Dr. Rebbeck oversees formal and informal training and research partnerships between Dana Farber investigators and trainees with international partners.

Cabazitaxel Plus Prednisone With Octreotide For Castration-Resistant Prostate Cancer (CRPC) Previously Treated With Docetaxel

ClinicalTrials.gov

2014-11-21

Diarrhea; Hormone-resistant Prostate Cancer; Recurrent Prostate Cancer; Stage I Prostate Cancer; Stage IIA Prostate Cancer; Stage IIB Prostate Cancer; Stage III Prostate Cancer; Stage IV Prostate Cancer

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.

Qualitative insights into how men with low-risk prostate cancer choosing active surveillance negotiate stress and uncertainty.

PubMed

Mader, Emily M; Li, Hsin H; Lyons, Kathleen D; Morley, Christopher P; Formica, Margaret K; Perrapato, Scott D; Irwin, Brian H; Seigne, John D; Hyams, Elias S; Mosher, Terry; Hegel, Mark T; Stewart, Telisa M

2017-05-08

Active surveillance is a management strategy for men diagnosed with early-stage, low-risk prostate cancer in which their cancer is monitored and treatment is delayed. This study investigated the primary coping mechanisms for men following the active surveillance treatment plan, with a specific focus on how these men interact with their social network as they negotiate the stress and uncertainty of their diagnosis and treatment approach. Thematic analysis of semi-structured interviews at two academic institutions located in the northeastern US. Participants include 15 men diagnosed with low-risk prostate cancer following active surveillance. The decision to follow active surveillance reflects the desire to avoid potentially life-altering side effects associated with active treatment options. Men on active surveillance cope with their prostate cancer diagnosis by both maintaining a sense of control over their daily lives, as well as relying on the support provided them by their social networks and the medical community. Social networks support men on active surveillance by encouraging lifestyle changes and serving as a resource to discuss and ease cancer-related stress. Support systems for men with low-risk prostate cancer do not always interface directly with the medical community. Spousal and social support play important roles in helping men understand and accept their prostate cancer diagnosis and chosen care plan. It may be beneficial to highlight the role of social support in interventions targeting the psychosocial health of men on active surveillance.

High-Intensity Focused Ultrasound in Treating Participants With Intermediate and High-risk Prostate Cancer

ClinicalTrials.gov

2018-06-13

Stage I Prostate Cancer AJCC v8; Stage II Prostate Cancer AJCC v8; Stage IIA Prostate Cancer AJCC v8; Stage IIB Prostate Cancer AJCC v8; Stage IIC Prostate Cancer AJCC v8; Stage III Prostate Cancer AJCC v8; Stage IIIA Prostate Cancer AJCC v8; Stage IIIB Prostate Cancer AJCC v8; Stage IIIC Prostate Cancer AJCC v8

The Role of c-Myc and miRNAs on EMT and the TGF-betaSwitch in Primary Intermediate Basal Cells Isolated From Prostate Cancer

DTIC Science & Technology

2013-03-01

beta alone and suggested that we attempt to understand the role of ras signaling, as myc is known to be activated downstream of ras( Compere et al...epithelial-mesenchymal transition and invasion in prostate cancer. Carcinogenesis 33, 1965-1975. Compere , S.J., Baldacci, P., Sharpe, A.H., Thompson

Imaging Prostate Cancer with Positron Emission Tomography

DTIC Science & Technology

2014-07-01

critical role in tumor development. The purpose of this proposal is to utilize fibroblast activation protein alpha ( FAP ) expression on TAFs within...based cell lines, which stably express eGFP and FAP . Ongoing experiments are focused on the in vitro and in vivo evaluation of each radiopharmaceutical...and on understanding the growth characteristics of each transfected cell line in vivo. 15. SUBJECT TERMS PET, Prostate Cancer, FAP , molecular

Four MicroRNAs Promote Prostate Cell Proliferation with Regulation of PTEN and Its Downstream Signals In Vitro

PubMed Central

Xue, Jing-lun; Chen, Jin-zhong

2013-01-01

Background Phosphatase and tensin homologue (PTEN), as a tumor suppressor, plays vital roles in tumorigenesis and progression of prostate cancer. However, the mechanisms of PTEN regulation still need further investigation. We here report that a combination of four microRNAs (miR-19b, miR-23b, miR-26a and miR-92a) promotes prostate cell proliferation by regulating PTEN and its downstream signals in vitro. Methodology/Principal Findings We found that the four microRNAs (miRNAs) could effectively suppress PTEN expression by directly interacting with its 3’ UTR in prostate epithelial and cancer cells. Under-expression of the four miRNAs by antisense neutralization up-regulates PTEN expression, while overexpression of the four miRNAs accelerates epithelial and prostate cancer cell proliferation. Furthermore, the expression of the four miRNAs could, singly or jointly, alter the expression of the key components in the phosphoinositide 3-kinase (PI3K)/Akt pathway, including PIK3CA, PIK3CD, PIK3R1 and Akt, along with their downstream signal, cyclin D1. Conclusions These results suggested that the four miRNAs could promote prostate cancer cell proliferation by co-regulating the expression of PTEN, PI3K/Akt pathway and cyclin D1 in vitro. These findings increase understanding of the molecular mechanisms of prostate carcinogenesis and progression, even provide valuable insights into the diagnosis, prognosis, and rational design of novel therapeutics for prostate cancer. PMID:24098737

Getting Black Men to Undergo Prostate Cancer Screening: The Role of Social Capital.

PubMed

Dean, Lorraine T; Subramanian, S V; Williams, David R; Armstrong, Katrina; Zubrinsky Charles, Camille; Kawachi, Ichiro

2015-09-01

Despite higher rates of prostate cancer-related mortality and later stage of prostate cancer diagnosis, Black/African American men are significantly less likely than non-Hispanic White men to use early detection screening tools, like prostate-specific antigen (PSA) testing for prostate cancer. Lower screening rates may be due, in part, to controversy over the value of prostate cancer screenings as part of routine preventive care for men, but Black men represent a high-risk group for prostate cancer that may still benefit from PSA testing. Exploring the role of social factors that might be associated with PSA testing can increase knowledge of what might promote screening behaviors for prostate cancer and other health conditions for which Black men are at high risk. Using multilevel logistic regression, this study analyzed self-report lifetime use of PSA test for 829 Black men older than 45 years across 381 Philadelphia census tracts. This study included individual demographic and aggregated social capital data from the Public Health Management Corporation's 2004, 2006, and 2008 waves of the Community Health Database, and sociodemographic characteristics from the 2000 U.S. Census. Each unit increase in community participation was associated with a 3 to 3.5 times greater likelihood of having had a PSA test (odds ratio = 3.35). Findings suggest that structural forms of social capital may play a role in screening behaviors for Black men in Philadelphia. A better understanding of the mechanism underlying the link between social capital and screening behaviors can inform how researchers and interventionists develop tools to promote screening for those who need it. © The Author(s) 2014.

Methodology to study the three-dimensional spatial distribution of prostate cancer and their dependence on clinical parameters

PubMed Central

Rojas, Kristians Diaz; Montero, Maria L.; Yao, Jorge; Messing, Edward; Fazili, Anees; Joseph, Jean; Ou, Yangming; Rubens, Deborah J.; Parker, Kevin J.; Davatzikos, Christos; Castaneda, Benjamin

2015-01-01

Abstract. A methodology to study the relationship between clinical variables [e.g., prostate specific antigen (PSA) or Gleason score] and cancer spatial distribution is described. Three-dimensional (3-D) models of 216 glands are reconstructed from digital images of whole mount histopathological slices. The models are deformed into one prostate model selected as an atlas using a combination of rigid, affine, and B-spline deformable registration techniques. Spatial cancer distribution is assessed by counting the number of tumor occurrences among all glands in a given position of the 3-D registered atlas. Finally, a difference between proportions is used to compare different spatial distributions. As a proof of concept, we compare spatial distributions from patients with PSA greater and less than 5  ng/ml and from patients older and younger than 60 years. Results suggest that prostate cancer has a significant difference in the right zone of the prostate between populations with PSA greater and less than 5  ng/ml. Age does not have any impact in the spatial distribution of the disease. The proposed methodology can help to comprehend prostate cancer by understanding its spatial distribution and how it changes according to clinical parameters. Finally, this methodology can be easily adapted to other organs and pathologies. PMID:26236756

Time-Resolved Spectroscopy and Near Infrared Imaging for Prostate Cancer Detection: Receptor-targeted and Native Biomarker

NASA Astrophysics Data System (ADS)

Pu, Yang

Optical spectroscopy and imaging using near-infrared (NIR) light provides powerful tools for non-invasive detection of cancer in tissue. Optical techniques are capable of quantitative reconstructions maps of tissue absorption and scattering properties, thus can map in vivo the differences in the content of certain marker chromophores and/or fluorophores in normal and cancerous tissues (for example: water, tryptophan, collagen and NADH contents). Potential clinical applications of optical spectroscopy and imaging include functional tumor detection and photothermal therapeutics. Optical spectroscopy and imaging apply contrasts from intrinsic tissue chromophores such as water, collagen and NADH, and extrinsic optical contrast agents such as Indocyanine Green (ICG) to distinguish disease tissue from the normal one. Fluorescence spectroscopy and imaging also gives high sensitivity and specificity for biomedical diagnosis. Recent developments on specific-targeting fluorophores such as small receptor-targeted dye-peptide conjugate contrast agent offer high contrast between normal and cancerous tissues hence provide promising future for early tumour detection. This thesis focus on a study to distinguish the cancerous prostate tissue from the normal prostate tissues with enhancement of specific receptor-targeted prostate cancer contrast agents using optical spectroscopy and imaging techniques. The scattering and absorption coefficients, and anisotropy factor of cancerous and normal prostate tissues were investigated first as the basis for the biomedical diagnostic and optical imaging. Understanding the receptors over-expressed prostate cancer cells and molecular target mechanism of ligand, two small ICG-derivative dye-peptides, namely Cypate-Bombesin Peptide Analogue Conjugate (Cybesin) and Cypate-Octreotate Peptide Conjugate (Cytate), were applied to study their clinical potential for human prostate cancer detection. In this work, the steady-state and time-resolved fluorescence spectroscopy of Cybesin (Cytate) in solution, and in cancerous and normal prostate tissues were studied. It was found that more Cybesin (Cytate) was uptaken in the cancerous prostate tissue than those in the normal tissue. The preferential uptake of Cybesin (Cytate) in cancerous tissue was used to image and distinguish cancerous areas from the normal tissue. To investigate rotational dynamics and fluorescence polarization anisotropy of the contrast agents in prostate tissues, an analytical model was used to extract the rotational times and polarization anisotropies, which were observed for higher values of Cybesin (Cytate)-stained cancerous prostate tissue in comparison with the normal tissue. These reflect changes of microstructures of cancerous and normal tissues and their different binding affinity with contrast agents. The results indicate that the use of optical spectroscopy and imaging combined with receptor-targeted contrast agents is a valuable tool to study microenvironmental changes of tissue, and detect prostate cancer in early stage.

Malakoplakia of the Prostate as a Mimicker of Prostate Cancer on Prostate Health Index and Magnetic Resonance Imaging-Fusion Prostate Biopsy: A Case Report.

PubMed

Heah, Nathaniel H; Tan, Teck Wei; Tan, Yung Khan

2017-01-01

Background: Isolated malakoplakia of the prostate is a rare inflammatory condition that has been clinically mistaken for prostatic malignancies. The development of Prostate Imaging Reporting and Data System (PI-RADS) classifications, and Prostate Health Index (PHI) has led to more accurate diagnosis of clinically significant disease and stratification of patients that may be at risk of prostate cancer. Case Presentation: We present a case of a 75-year-old male who was on follow-up with our hospital for elevated prostate specific antigen (PSA). He was admitted for an episode of urosepsis, which was treated with antibiotics and subsequently underwent further workup and was found to have a raised PHI, as well as a high PI-RADS classification and was later found to have malakoplakia based on histology of prostate tissue obtained during targeted magnetic resonance imaging (MRI)-guided fusion prostate biopsy. Conclusion: To our understanding, this is the first case where a prostate lesion has been labeled as a PI-RADS 5 lesion, with elevated PHI that has subsequently been proven histologically to be malakoplakia. An important possible confounder is the interval between the MRI and the episode of urosepsis and it is well known that urosepsis can affect the PSA and MRI result. We present this case to highlight the potential for a false diagnosis of prostate cancer, in spite of laboratory and radiological findings.

Inherited variation in circadian rhythm genes and risks of prostate cancer and three other cancer sites in combined cancer consortia.

PubMed

Gu, Fangyi; Zhang, Han; Hyland, Paula L; Berndt, Sonja; Gapstur, Susan M; Wheeler, William; Ellipse Consortium, The; Amos, Christopher I; Bezieau, Stephane; Bickeböller, Heike; Brenner, Hermann; Brennan, Paul; Chang-Claude, Jenny; Conti, David V; Doherty, Jennifer Anne; Gruber, Stephen B; Harrison, Tabitha A; Hayes, Richard B; Hoffmeister, Michael; Houlston, Richard S; Hung, Rayjean J; Jenkins, Mark A; Kraft, Peter; Lawrenson, Kate; McKay, James; Markt, Sarah; Mucci, Lorelei; Phelan, Catherine M; Qu, Conghui; Risch, Angela; Rossing, Mary Anne; Wichmann, H-Erich; Shi, Jianxin; Schernhammer, Eva; Yu, Kai; Landi, Maria Teresa; Caporaso, Neil E

2017-11-01

Circadian disruption has been linked to carcinogenesis in animal models, but the evidence in humans is inconclusive. Genetic variation in circadian rhythm genes provides a tool to investigate such associations. We examined associations of genetic variation in nine core circadian rhythm genes and six melatonin pathway genes with risk of colorectal, lung, ovarian and prostate cancers using data from the Genetic Associations and Mechanisms in Oncology (GAME-ON) network. The major results for prostate cancer were replicated in the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial, and for colorectal cancer in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). The total number of cancer cases and controls was 15,838/18,159 for colorectal, 14,818/14,227 for prostate, 12,537/17,285 for lung and 4,369/9,123 for ovary. For each cancer site, we conducted gene-based and pathway-based analyses by applying the summary-based Adaptive Rank Truncated Product method (sARTP) on the summary association statistics for each SNP within the candidate gene regions. Aggregate genetic variation in circadian rhythm and melatonin pathways were significantly associated with the risk of prostate cancer in data combining GAME-ON and PLCO, after Bonferroni correction (p pathway  < 0.00625). The two most significant genes were NPAS2 (p gene  = 0.0062) and AANAT (p gene  = 0.00078); the latter being significant after Bonferroni correction. For colorectal cancer, we observed a suggestive association with the circadian rhythm pathway in GAME-ON (p pathway  = 0.021); this association was not confirmed in GECCO (p pathway  = 0.76) or the combined data (p pathway  = 0.17). No significant association was observed for ovarian and lung cancer. These findings support a potential role for circadian rhythm and melatonin pathways in prostate carcinogenesis. Further functional studies are needed to better understand the underlying biologic mechanisms. © 2017 UICC.

Genes involved in prostate cancer progression determine MRI visibility

PubMed Central

Li, Ping; You, Sungyong; Nguyen, Christopher; Wang, Yanping; Kim, Jayoung; Sirohi, Deepika; Ziembiec, Asha; Luthringer, Daniel; Lin, Shih-Chieh; Daskivich, Timothy; Wu, Jonathan; Freeman, Michael R; Saouaf, Rola; Li, Debiao; Kim, Hyung L.

2018-01-01

MRI is used to image prostate cancer and target tumors for biopsy or therapeutic ablation. The objective was to understand the biology of tumors not visible on MRI that may go undiagnosed and untreated. Methods: Prostate cancers visible or invisible on multiparametric MRI were macrodissected and examined by RNAseq. Differentially expressed genes (DEGs) based on MRI visibility status were cross-referenced with publicly available gene expression databases to identify genes associated with disease progression. Genes with potential roles in determining MRI visibility and disease progression were knocked down in murine prostate cancer xenografts, and imaged by MRI. Results: RNAseq identified 1,654 DEGs based on MRI visibility status. Comparison of DEGs based on MRI visibility and tumor characteristics revealed that Gleason score (dissimilarity test, p<0.0001) and tumor size (dissimilarity test, p<0.039) did not completely determine MRI visibility. Genes in previously reported prognostic signatures significantly correlated with MRI visibility suggesting that MRI visibility was prognostic. Cross-referencing DEGs with external datasets identified four genes (PHYHD1, CENPF, ALDH2, GDF15) that predict MRI visibility, progression free survival and metastatic deposits. Genetic modification of a human prostate cancer cell line to induce miR-101 and suppress CENPF decreased cell migration and invasion. As prostate cancer xenografts in mice, these cells had decreased visibility on diffusion weighted MRI and decreased perfusion, which correlated with immunostaining showing decreased cell density and proliferation. Conclusions: Genes involved in prostate cancer prognosis and metastasis determine MRI visibility, indicating that MRI visibility has prognostic significance. MRI visibility was associated with genetic features linked to poor prognosis. PMID:29556354

Variation in prostate cancer treatment associated with population density of the county of residence.

PubMed

Cary, C; Odisho, A Y; Cooperberg, M R

2016-06-01

We sought to assess variation in the primary treatment of prostate cancer by examining the effect of population density of the county of residence on treatment for clinically localized prostate cancer and quantify variation in primary treatment attributable to the county and state level. A total 138 226 men with clinically localized prostate cancer in the Surveillance, Epidemiology and End Result (SEER) database in 2005 through 2008 were analyzed. The main association of interest was between prostate cancer treatment and population density using multilevel hierarchical logit models while accounting for the random effects of counties nested within SEER regions. To quantify the effect of county and SEER region on individual treatment, the percent of total variance in treatment attributable to county of residence and SEER site was estimated with residual intraclass correlation coefficients. Men with localized prostate cancer in metropolitan counties had 23% higher odds of being treated with surgery or radiation compared with men in rural counties, controlling for number of urologists per county as well as clinical and sociodemographic characteristics. Three percent (95% confidence interval (CI): 1.2-6.2%) of the total variation in treatment was attributable to SEER site, while 6% (95% CI: 4.3-9.0%) of variation was attributable to county of residence, adjusting for clinical and sociodemographic characteristics. Variation in treatment for localized prostate cancer exists for men living in different population-dense counties of the country. These findings highlight the importance of comparative effectiveness research to improve understanding of this variation and lead to a reduction in unwarranted variation.

Three-Dimensional Magnetic Resonance Spectroscopic Imaging of Brain and Prostate Cancer1

PubMed Central

Kurhanewicz, John; Vigneron, Daniel B; Nelson, Sarah J

2000-01-01

Abstract Clinical applications of magnetic resonance spectroscopic imaging (MRSI) for the study of brain and prostate cancer have expanded significantly over the past 10 years. Proton MRSI studies of the brain and prostate have demonstrated the feasibility of noninvasively assessing human cancers based on metabolite levels before and after therapy in a clinically reasonable amount of time. MRSI provides a unique biochemical “window” to study cellular metabolism noninvasively. MRSI studies have demonstrated dramatic spectral differences between normal brain tissue (low choline and high N-acetyl aspartate, NAA) and prostate (low choline and high citrate) compared to brain (low NAA, high choline) and prostate (low citrate, high choline) tumors. The presence of edema and necrosis in both the prostate and brain was reflected by a reduction of the intensity of all resonances due to reduced cell density. MRSI was able to discriminate necrosis (absence of all metabolites, except lipids and lactate) from viable normal tissue and cancer following therapy. The results of current MRSI studies also provide evidence that the magnitude of metabolic changes in regions of cancer before therapy as well as the magnitude and time course of metabolic changes after therapy can improve our understanding of cancer aggressiveness and mechanisms of therapeutic response. Clinically, combined MRI/MRSI has already demonstrated the potential for improved diagnosis, staging and treatment planning of brain and prostate cancer. Additionally, studies are under way to determine the accuracy of anatomic and metabolic parameters in providing an objective quantitative basis for assessing disease progression and response to therapy. PMID:10933075

Assessing the acceptability and usability of an interactive serious game in aiding treatment decisions for patients with localized prostate cancer.

PubMed

Reichlin, Lindsey; Mani, Nithya; McArthur, Kara; Harris, Amy M; Rajan, Nithin; Dacso, Clifford C

2011-01-12

Men diagnosed with localized prostate cancer face a potentially life-altering treatment decision that can be overwhelming. Enhancing patient knowledge through education can significantly reduce feelings of uncertainty while simultaneously increasing confidence in decision making. Serious games have been shown in other populations to increase health knowledge and assist with the health decision-making process. We developed an interactive serious game, Time After Time, which translates evidence-based treatment outcome data into an accessible and understandable format that men can utilize in their prostate cancer treatment decision-making process. The game specifically aims to raise men's awareness and understanding of the impact of health-related quality of life issues associated with the major treatment options and to enrich their conversations with their health care providers. This study determined the acceptability and usability of the alpha version of Time After Time, an interactive decision aid for men diagnosed with localized prostate cancer, in order to inform future iterations of the serious game. The study employed a mixed methods approach to assess the acceptability and usability of the Time After Time serious game using qualitative focus groups and a quantitative Likert scale survey. A total of 13 men who had already completed treatment for localized prostate cancer completed the survey and participated in focus group meetings. The majority of the study participants rated Time After Time as an appropriate decision tool for localized prostate cancer and verified that it meets its goals of increasing focus on side effects and generating questions for the patient's health care team. However, participants also expressed concerns about game usability and the diversity of information covered regarding treatment options and potential treatment outcomes. Serious games are a promising approach to health education and decision support for older men. Participants were receptive to the idea of a serious game as a decision aid in localized prostate cancer. However, usability issues are a major concern for this demographic, as is clarity and transparency of data sources.

Assessing the Acceptability and Usability of an Interactive Serious Game in Aiding Treatment Decisions for Patients with Localized Prostate Cancer

PubMed Central

2011-01-01

Background Men diagnosed with localized prostate cancer face a potentially life-altering treatment decision that can be overwhelming. Enhancing patient knowledge through education can significantly reduce feelings of uncertainty while simultaneously increasing confidence in decision making. Serious games have been shown in other populations to increase health knowledge and assist with the health decision-making process. We developed an interactive serious game, Time After Time, which translates evidence-based treatment outcome data into an accessible and understandable format that men can utilize in their prostate cancer treatment decision-making process. The game specifically aims to raise men’s awareness and understanding of the impact of health-related quality of life issues associated with the major treatment options and to enrich their conversations with their health care providers. Objective This study determined the acceptability and usability of the alpha version of Time After Time, an interactive decision aid for men diagnosed with localized prostate cancer, in order to inform future iterations of the serious game. Methods The study employed a mixed methods approach to assess the acceptability and usability of the Time After Time serious game using qualitative focus groups and a quantitative Likert scale survey. Results A total of 13 men who had already completed treatment for localized prostate cancer completed the survey and participated in focus group meetings. The majority of the study participants rated Time After Time as an appropriate decision tool for localized prostate cancer and verified that it meets its goals of increasing focus on side effects and generating questions for the patient’s health care team. However, participants also expressed concerns about game usability and the diversity of information covered regarding treatment options and potential treatment outcomes. Conclusions Serious games are a promising approach to health education and decision support for older men. Participants were receptive to the idea of a serious game as a decision aid in localized prostate cancer. However, usability issues are a major concern for this demographic, as is clarity and transparency of data sources. PMID:21239374

Selenium and Vitamin E for Prostate Cancer: Post-SELECT (Selenium and Vitamin E Cancer Prevention Trial) Status

PubMed Central

Ledesma, Mark C; Jung-Hynes, Brittney; Schmit, Travis L; Kumar, Raj; Mukhtar, Hasan; Ahmad, Nihal

2011-01-01

Various formulations of selenium and vitamin E, both essential human dietary components, have been shown to possess a therapeutic and preventive effect against prostate cancer. Fortuitous results of clinical trials also implied a risk-reduction effect of selenium and vitamin E supplements. The Selenium and Vitamin E Cancer Prevention Trial (SELECT), using oral selenium and vitamin E supplementation in disease-free volunteers, was designed to test a prostate cancer chemoprevention hypothesis. SELECT was terminated early because of both safety concerns and negative data for the formulations and doses given. Here, we review and discuss the studies done before and since the inception of SELECT, as well as the parameters of the trial itself. We believe that there is a lack of appropriate in vivo preclinical studies on selenium and vitamin E despite many promising in vitro studies on these agents. It seems that the most effective doses and formulations of these agents for prostate cancer chemoprevention have yet to be tested. Also, improved understanding of selenium and vitamin E biology may facilitate the discovery of these doses and formulations. PMID:20882260

Fifteen-year Outcomes Following Conservative Management Among Men Aged 65 Years or Older with Localized Prostate Cancer.

PubMed

Lu-Yao, Grace L; Albertsen, Peter C; Moore, Dirk F; Lin, Yong; DiPaola, Robert S; Yao, Siu-Long

2015-11-01

To understand the threat posed by localized prostate cancer and the potential impact of surgery or radiation, patients and healthcare providers require information on long-term outcomes following conservative management. To describe 15-yr survival outcomes and cancer therapy utilization among men 65 years and older managed conservatively for newly diagnosed localized prostate cancer. This is a population-based cohort study with participants living in predefined geographic areas covered by the Surveillance, Epidemiology, and End Results program. The study includes 31 137 Medicare patients aged ≥65 yr diagnosed with localized prostate cancer in 1992-2009 who initially received conservative management (no surgery, radiotherapy, cryotherapy, or androgen deprivation therapy [ADT]). All patients were followed until death or December 31, 2009 (for prostate cancer-specific mortality [PCSM]) and December 31, 2011 (for overall mortality). Competing-risk analyses were used to examine PCSM, overall mortality, and utilization of cancer therapies. The 15-yr risk of PCSM for men aged 65-74 yr diagnosed with screening-detected prostate cancer was 5.7% (95% confidence interval [CI] 3.7-8.0%) for T1c Gleason 5-7 and 22% (95% CI 16-35%) for Gleason 8-10 disease. After 15 yr of follow-up, 24% (95% CI 21-27%) of men aged 65-74 yr with screening-detected Gleason 5-7 cancer received ADT. The corresponding result for men with Gleason 8-10 cancer was 38% (95% CI 32-44%). The major study limitations are the lack of data for men aged <65 yr and detailed clinical information associated with secondary cancer therapy. The 15-yr outcomes following conservative management of newly diagnosed Gleason 5-7 prostate cancer among men aged ≥65 yr are excellent. Men with Gleason 8-10 disease managed conservatively face a significant risk of PCSM. We examined the long-term survival outcomes for a large group of patients diagnosed with localized prostate cancer who did not have surgery, radiotherapy, cryotherapy, or androgen deprivation therapy in the first 6 mo after cancer diagnosis. We found that the 15-yr disease-specific survival is excellent for men diagnosed with Gleason 5-7 disease. The data support conservative management as a reasonable choice for elderly patients with low-grade localized prostate cancer. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Pre-screening Discussions and Prostate-Specific Antigen Testing for Prostate Cancer Screening

PubMed Central

Li, Jun; Zhao, Guixiang; Hall, Ingrid J.

2015-01-01

Introduction For many men, the net benefit of prostate cancer screening with prostate-specific antigen (PSA) tests may be small. Many major medical organizations have issued recommendations for prostate cancer screening, stressing the need for shared decision making before ordering a test. The purpose of this study is to better understand associations between discussions about benefits and harms of PSA testing and uptake of the test among men aged ≥40 years. Methods Associations between pre-screening discussions and PSA testing were examined using self-reported data from the 2012 Behavioral Risk Factor Surveillance System. Unadjusted prevalence of PSA testing was estimated and AORs were calculated using logistic regression in 2014. Results The multivariate analysis showed that men who had ever discussed advantages of PSA testing only or discussed both advantages and disadvantages were more likely, respectively, to report having had a test within the past year than men who had no discussions (p<0.001). In addition, men who had only discussed the disadvantages of PSA testing with their healthcare providers were more likely (AOR=2.75, 95% CI=2.00, 3.79) to report getting tested than men who had no discussions. Conclusions Discussions of the benefits or harms of PSA testing are positively associated with increased uptake of the test. Given the conflicting recommendations for prostate cancer screening and increasing importance of shared decision making, this study points to the need for understanding how pre-screening discussions are being conducted in clinical practice and the role played by patients’ values and preferences in decisions about PSA testing. PMID:25997905

Pre-screening Discussions and Prostate-Specific Antigen Testing for Prostate Cancer Screening.

PubMed

Li, Jun; Zhao, Guixiang; Hall, Ingrid J

2015-08-01

For many men, the net benefit of prostate cancer screening with prostate-specific antigen (PSA) tests may be small. Many major medical organizations have issued recommendations for prostate cancer screening, stressing the need for shared decision making before ordering a test. The purpose of this study is to better understand associations between discussions about benefits and harms of PSA testing and uptake of the test among men aged ≥40 years. Associations between pre-screening discussions and PSA testing were examined using self-reported data from the 2012 Behavioral Risk Factor Surveillance System. Unadjusted prevalence of PSA testing was estimated and AORs were calculated using logistic regression in 2014. The multivariate analysis showed that men who had ever discussed advantages of PSA testing only or discussed both advantages and disadvantages were more likely, respectively, to report having had a test within the past year than men who had no discussions (p<0.001). In addition, men who had only discussed the disadvantages of PSA testing with their healthcare providers were more likely (AOR=2.75, 95% CI=2.00, 3.79) to report getting tested than men who had no discussions. Discussions of the benefits or harms of PSA testing are positively associated with increased uptake of the test. Given the conflicting recommendations for prostate cancer screening and increasing importance of shared decision making, this study points to the need for understanding how pre-screening discussions are being conducted in clinical practice and the role played by patients' values and preferences in decisions about PSA testing. Published by Elsevier Inc.

Lineage plasticity-mediated therapy resistance in prostate cancer.

PubMed

Blee, Alexandra M; Huang, Haojie

2018-06-12

Therapy resistance is a significant challenge for prostate cancer treatment in clinic. Although targeted therapies such as androgen deprivation and androgen receptor (AR) inhibition are effective initially, tumor cells eventually evade these strategies through multiple mechanisms. Lineage reprogramming in response to hormone therapy represents a key mechanism that is increasingly observed. The studies in this area have revealed specific combinations of alterations present in adenocarcinomas that provide cells with the ability to transdifferentiate and perpetuate AR-independent tumor growth after androgen-based therapies. Interestingly, several master regulators have been identified that drive plasticity, some of which also play key roles during development and differentiation of the cell lineages in the normal prostate. Thus, further study of each AR-independent tumor type and understanding underlying mechanisms are warranted to develop combinational therapies that combat lineage plasticity in prostate cancer.

Oligometastatic prostate cancer: shaping the definition with molecular imaging and an improved understanding of tumor biology.

PubMed

Joice, Gregory A; Rowe, Steven P; Pienta, Kenneth J; Gorin, Michael A

2017-11-01

The aim of this review is to discuss how novel imaging modalities and molecular markers are shaping the definition of oligometastatic prostate cancer. To effectively classify a patient as having oligometastatic prostate cancer, diagnostic tests must be sensitive enough to detect subtle sites of metastatic disease. Conventional imaging modalities can readily detect widespread polymetastatic disease but do not have the sensitivity necessary to reliably classify patients as oligometastatic. Molecular imaging using both metabolic- and molecularly-targeted radiotracers has demonstrated great promise in aiding in our ability to define the oligometastatic state. Perhaps the most promising data to date have been generated with radiotracers targeting prostate-specific membrane antigen. In addition, early studies are beginning to define biologic markers in the oligometastatic state that may be indicative of disease with minimal metastatic potential. Recent developments in molecular imaging have allowed for improved detection of metastatic prostate cancer allowing for more accurate staging of patients with oligometastatic disease. Future development of biologic markers may assist in defining the oligometastatic state and determining prognosis.

Men, culture and hegemonic masculinity: understanding the experience of prostate cancer.

PubMed

Wall, David; Kristjanson, Linda

2005-06-01

Following a diagnosis of, and treatment for prostate cancer, there is an expectation that men will cope with, adjust to and accept the psychosocial impact on their lives and relationships. Yet, there is a limited qualitative world literature investigating the psychosocial experience of prostate cancer, and almost no literature exploring how masculinity mediates in such an experience. This paper will suggest that the experience of prostate cancer, the process by which it is investigated, and the way in which it is understood has been shaped by an essentialist interpretation of gender, exemplified by hegemonic masculinity as the archetypal mechanism of male adaptation. In response to this static and limiting view of masculinity, this paper will offer a reframe of hegemonic masculinity. This reframe, being more aligned with common experience, will portray masculinity as a dynamic and contextual construct, better understood as one of a number of cultural reference points around which each man organises and adopts behaviour. It will be suggested that the extant literature, in being organised around hegemonic masculinity, obfuscates the experience of prostate cancer and acts to render covert any collateral masculinities, public or private, that may also be operating.

Recent advances in circulating tumor cells and cell-free DNA in metastatic prostate cancer: a review.

PubMed

Parimi, Sunil; Ko, Jenny J

2017-10-01

The treatment landscape of metastatic prostate cancer has changed dramatically over the past five years. As new discoveries are made and further novel therapies become available, there is a heightened urgency to develop biomarkers that can guide prognoses and predict therapy responses. Circulating tumor cells (CTCs) and cell-free circulating tumor DNA (ctDNA) in the blood have emerged as potential promising tumor avatars. Areas covered: In this review, we describe technological breakthroughs and clinical implementation of the CTCs and ctDNA. We also discuss the key challenges that must be overcome before circulating blood-based biomarkers can be universally adopted into the management of patients with metastatic prostate cancer. Expert commentary: Both CTCs and ctDNA have the potential to be incorporated into routine patient care, with increasing numbers of prospective trials incorporating them into clinical designs. CTCs and ctDNA will thus have an increasingly valuable role in augmenting our understanding of prostate cancer at a molecular level, aiding in prognostication of prostate cancer patients, acting as a surrogate for OS in clinical trials, and helping us prioritize our treatment selections by elucidating resistance mechanisms.

Socioeconomic disadvantage but not remoteness affects short-term survival in prostate cancer: A population-based study using competing risks.

PubMed

Thomas, Audrey A; Pearce, Alison; Sharp, Linda; Gardiner, Robert Alexander; Chambers, Suzanne; Aitken, Joanne; Molcho, Michal; Baade, Peter

2017-04-01

We examined how sociodemographic, clinical and area-level factors are related to short-term prostate cancer mortality versus mortality from other causes, a crucial distinction for this disease that disproportionately affects men older than 60 years. We applied competing risk survival models to administrative data from the Queensland Cancer Registry (Australia) for men diagnosed with prostate cancer between January 2005 and July 2007, including stratification by Gleason score. The men (n = 7393) in the study cohort had a median follow-up of 5 years 3 months. After adjustment, remoteness and area-level disadvantage were not significantly associated with prostate cancer mortality. However, area-level disadvantage had a significant negative relationship with hazard of death from a cause other than prostate cancer within 7 years; compared with those living in the most advantaged areas, the likelihood of mortality was higher for those in the most disadvantaged (subhazard ratio [SHR] = 1.39; 95% CI, 1.01-1.90; P = 0.041), disadvantaged (SHR = 1.51; 95% CI, 1.14-2.00; P = 0.004), middle (SHR = 1.34; 95% CI, 1.02-1.75; P = 0.034) and advantaged areas (SHR = 1.44; 95% CI, 1.09-1.89; P = 0.009). Those with Gleason score of 7 and higher had a lower hazard of prostate cancer mortality if they were living with a partner, whereas those with lower Gleason scores and living a partner had lower hazards of other-cause mortality. Understanding why men living in more disadvantaged areas have higher risk of non-prostate cancer mortality should be a priority. © 2016 John Wiley & Sons Australia, Ltd.

Human adipose-derived mesenchymal stromal cell pigment epithelium-derived factor cytotherapy modifies genetic and epigenetic profiles of prostate cancer cells.

PubMed

Zolochevska, Olga; Shearer, Joseph; Ellis, Jayne; Fokina, Valentina; Shah, Forum; Gimble, Jeffrey M; Figueiredo, Marxa L

2014-03-01

Adipose-derived mesenchymal stromal cells (ASCs) are promising tools for delivery of cytotherapy against cancer. However, ASCs can exert profound effects on biological behavior of tumor cells. Our study aimed to examine the influence of ASCs on gene expression and epigenetic methylation profiles of prostate cancer cells as well as the impact of expressing a therapeutic gene on modifying the interaction between ASCs and prostate cancer cells. ASCs were modified by lentiviral transduction to express either green fluorescent protein as a control or pigment epithelium-derived factor (PEDF) as a therapeutic molecule. PC3 prostate cancer cells were cultured in the presence of ASC culture-conditioned media (CCM), and effects on PC3 or DU145. Ras cells were examined by means of real-time quantitative polymerase chain reaction, EpiTect methyl prostate cancer-focused real-time quantitative polymerase chain reaction arrays, and luciferase reporter assays. ASCs transduced with lentiviral vectors were able to mediate expression of several tumor-inhibitory genes, some of which correlated with epigenetic methylation changes on cocultured PC3 prostate cancer cells. When PC3 cells were cultured with ASC-PEDF CCM, we observed a shift in the balance of gene expression toward tumor inhibition, which suggests that PEDF reduces the potential tumor-promoting activity of unmodified ASCs. These results suggest that ASC-PEDF CCM can promote reprogramming of tumor cells in a paracrine manner. An improved understanding of genetic and epigenetic events in prostate cancer growth in response to PEDF paracrine therapy would enable a more effective use of ASC-PEDF, with the goal of achieving safer yet more potent anti-tumor effects. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Tumor Markers

MedlinePlus

... on its own to screen for cancer. For example, the prostate-specific antigen (PSA) test , which measures the level of PSA in the ... Targeted Cancer Therapies Understanding Cancer ... Institute.” Please note that blog posts that are written by individuals from outside the ...

The curative management of synchronous rectal and prostate cancer

PubMed Central

Kavanagh, Dara O; Martin, Joseph; Small, Cormac; Joyce, Myles R; Faul, Clare M; Kelly, Paul J; O'Riordain, Michael; Gillham, Charles M; Armstrong, John G; Salib, Osama; McNamara, Deborah A; McVey, Gerard; O'Neill, Brian D P

2016-01-01

Objective: Neoadjuvant “long-course” chemoradiation is considered a standard of care in locally advanced rectal cancer. In addition to prostatectomy, external beam radiotherapy and brachytherapy with or without androgen suppression (AS) are well established in prostate cancer management. A retrospective review of ten cases was completed to explore the feasibility and safety of applying these standards in patients with dual pathology. To our knowledge, this is the largest case series of synchronous rectal and prostate cancers treated with curative intent. Methods: Eligible patients had synchronous histologically proven locally advanced rectal cancer (defined as cT3-4Nx; cTxN1-2) and non-metastatic prostate cancer (pelvic nodal disease permissible). Curative treatment was delivered to both sites simultaneously. Follow-up was as per institutional guidelines. Acute and late toxicities were reviewed, and a literature search performed. Results: Pelvic external beam radiotherapy (RT) 45–50.4 Gy was delivered concurrent with 5-fluorouracil (5FU). Prostate total dose ranged from 70.0 to 79.2 Gy. No acute toxicities occurred, excluding AS-induced erectile dysfunction. Nine patients proceeded to surgery, and one was managed expectantly. Three relapsed with metastatic colorectal cancer, two with metastatic prostate cancer. Five patients have no evidence of recurrence, and four remain alive with metastatic disease. With a median follow-up of 2.2 years (range 1.2–6.3 years), two significant late toxicities occurred; G3 proctitis in a patient receiving palliative bevacizumab and a G3 anastomotic stricture precluding stoma reversal. Conclusion: Patients proceeding to synchronous radical treatment of both primary sites should receive 45–50.4 Gy pelvic RT with infusional 5FU. Prostate dose escalation should be given with due consideration to the potential impact of prostate cancer on patient survival, as increasing dose may result in significant late morbidity. Review of published series explores the possibility of prostate brachytherapy as an alternative method of boost delivery. Frequent use of bevacizumab in metastatic rectal cancer may compound late rectal morbidity in this cohort. Advances in knowledge: To our knowledge, this is the largest case series of synchronous rectal and prostate cancers treated with curative intent. This article contributes to the understanding of how best to approach definitive treatment in these patients. PMID:26539631

Clinically localized prostate cancer in 2017: A review of comparative effectiveness.

PubMed

Lavery, Hugh J; Cooperberg, Matthew R

2017-02-01

Introducing the topic of comparative effectiveness for prostate cancer treatments with a reminder of the disease's heterogeneity risks tautology. However, the profound variation both in this cancer's biology and its clinical course is increasingly widely recognized, while management alternatives for clinically localized prostate cancer have exploded. Available options now include active surveillance, multiple surgical approaches to prostatectomy, various forms of external-beam and interstitial radiation, and a growing list of energy ablative technologies. Each treatment option has its own efficacy rate as well as its own set of complications, side effects and financial costs. Difficulties comparing these options, together with the high prevalence of the disease, led the Institute of Medicine to include localized prostate cancer among the top 25 priority conditions for future comparative effectiveness research. The sheer volume of possible treatment options, with their individual risks and benefits, can be confusing for patients and clinicians to research, understand and explain. To help clinicians navigate these treatment options, we have assembled this Urologic Oncology Seminar on the comparative effectiveness of treatments for clinically localized prostate cancer. The articles focus on high quality evidence-based medicine and most have included useful tables summarizing seminal trials and available resources. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Older cancer patients in cancer clinical trials are underrepresented. Systematic literature review of almost 5000 meta- and pooled analyses of phase III randomized trials of survival from breast, prostate and lung cancer.

PubMed

Dunn, Cita; Wilson, Andrew; Sitas, Freddy

2017-12-01

Older people represent increasing proportions of the population with cancer. To understand the representivity of cancer treatments in older people, we performed a systematic literature review using PRISMA guidelines of the age distribution of clinical trial participants for three leading cancer types, namely breast, prostate, and lung. We used PubMed to identify articles detailing meta or pooled-analyses of phase III, randomised controlled trials (RCTs) of survival for breast, prostate and lung cancer, published ≤5 years from 2016. We compared the age distribution of participants to that of these cancers for "More developed regions". 4993 potential papers were identified, but only three papers on breast cancer, three on lung cancer, and none on prostate cancer presented the age distribution of their participants. Except for one paper of breast cancer, participants ≥70 years in all other papers were underrepresented. We recommend the age distribution of patients be clearly reported in all clinical trials, as per guidelines. Clinical trials ought to be more representative of the populations most affected by the disease for which treatments are being tested. This should lead to better knowledge of effectiveness of treatments and better translation of trial results to optimal care of older cancer patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Genetics Home Reference: prostate cancer

MedlinePlus

... prostate cancer Genetic Testing Registry: Prostate cancer aggressiveness quantitative trait locus on chromosome 19 Genetic Testing Registry: ... OMIM (25 links) PROSTATE CANCER PROSTATE CANCER AGGRESSIVENESS QUANTITATIVE TRAIT LOCUS ON CHROMOSOME 19 PROSTATE CANCER ANTIGEN ...

Association between tumor necrosis factor-alpha gene polymorphisms and prostate cancer risk: a meta-analysis.

PubMed

Ma, Liping; Zhao, Jiangyang; Li, Taijie; He, Yu; Wang, Jian; Xie, Li; Qin, Xue; Li, Shan

2014-03-25

Tumor necrosis factor-alpha (TNF-α) is an important inflammatory cytokine that may play a role in controlling the progression of prostate cancer. Two common polymorphisms in the TNF-α gene, -308G/A and -238C/T, have been suggested to alter the risk for prostate cancer, but the results have been inconclusive so far. In order to obtain a better understanding of the effects of these two polymorphisms on prostate cancer risk, all available studies were considered in a meta-analysis. We conducted a comprehensive literature search in the Cochrane Library, PubMed, EMBASE, Chinese Biomedical Literature database (CBM), and the China National Knowledge Infrastructure (CNKI). The associations were evaluated by calculating the pooled odds ratio (OR) with 95% confidence interval (95% CI). In this meta-analysis, we included 14 studies with 5,757 patients and 6,137 control subjects for the TNF-α-308G/A polymorphism and 1,967 patients and 2,004 control subjects for the TNF-α-238C/T polymorphism. A significantly increased prostate cancer risk was found to be associated with the TNF-α-308C/T polymorphism in studies with healthy volunteers (AA + AG vs. GG: OR = 1.531, 95% CI = 1.093-2.145; P = 0.013; AG vs. GG: OR = 1.477, 95% CI = 1.047-2.085; P = 0.026). No significant association was found between the TNF-α-238G/A polymorphism and prostate cancer risk in the overall or subgroup analyses. There was no risk of publication bias in this meta-analysis. Our results suggest that while the TNF-α-238G/A polymorphism may not be associated with prostate cancer the TNF-α-308C/T polymorphism may significantly contribute to prostate cancer susceptibility in healthy volunteers. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1629288120116301.

The use of collagen-based scaffolds to simulate prostate cancer bone metastases with potential for evaluating delivery of nanoparticulate gene therapeutics.

PubMed

Fitzgerald, Kathleen A; Guo, Jianfeng; Tierney, Erica G; Curtin, Caroline M; Malhotra, Meenakshi; Darcy, Raphael; O'Brien, Fergal J; O'Driscoll, Caitriona M

2015-10-01

Prostate cancer bone metastases are a leading cause of cancer-related death in men with current treatments offering only marginally improved rates of survival. Advances in the understanding of the genetic basis of prostate cancer provide the opportunity to develop gene-based medicines capable of treating metastatic disease. The aim of this work was to establish a 3D cell culture model of prostate cancer bone metastasis using collagen-based scaffolds, to characterise this model, and to assess the potential of the model to evaluate delivery of gene therapeutics designed to target bone metastases. Two prostate cancer cell lines (PC3 and LNCaP) were cultured in 2D standard culture and compared to 3D cell growth on three different collagen-based scaffolds (collagen and composites of collagen containing either glycosaminoglycan or nanohydroxyapatite). The 3D model was characterised for cell proliferation, viability and for matrix metalloproteinase (MMP) enzyme and Prostate Specific Antigen (PSA) secretion. Chemosensitivity to docetaxel treatment was assessed in 2D in comparison to 3D. Nanoparticles (NPs) containing siRNA formulated using a modified cyclodextrin were delivered to the cells on the scaffolds and gene silencing was quantified. Both prostate cancer cell lines actively infiltrated and proliferated on the scaffolds. Cell culture in 3D resulted in reduced levels of MMP1 and MMP9 secretion in PC3 cells. In contrast, LNCaP cells grown in 3D secreted elevated levels of PSA, particularly on the scaffold composed of collagen and glycosaminoglycans. Both cell lines grown in 3D displayed increased resistance to docetaxel treatment. The cyclodextrin.siRNA nanoparticles achieved cellular uptake and knocked down the endogenous GAPDH gene in the 3D model. In conclusion, development of a novel 3D cell culture model of prostate cancer bone metastasis has been initiated resulting, for the first time, in the successful delivery of gene therapeutics in a 3D in vitro model. Further enhancement of this model will help elucidate the pathogenesis of prostate cancer and also accelerate the design of effective therapies which can penetrate into the bone microenvironment for prostate cancer therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Androgen receptor variation affects prostate cancer progression and drug resistance.

PubMed

McCrea, Edel; Sissung, Tristan M; Price, Douglas K; Chau, Cindy H; Figg, William D

2016-12-01

Significant therapeutic progress has been made in treating prostate cancer in recent years. Drugs such as enzalutamide, abiraterone, and cabazitaxel have expanded the treatment armamentarium, although it is not completely clear which of these drugs are the most-effective option for individual patients. Moreover, such advances have been tempered by the development of therapeutic resistance. The purpose of this review is to summarize the current literature pertaining to the biochemical effects of AR variants and their consequences on prostate cancer therapies at both the molecular level and in clinical treatment. We address how these AR splice variants and mutations affect tumor progression and therapeutic resistance and discuss potential novel therapeutic strategies under development. It is hoped that these therapies can be administered with increasing precision as tumor genotyping methods become more sophisticated, thereby lending clinicians a better understanding of the underlying biology of prostate tumors in individual patients. Published by Elsevier Ltd.

Suitability of prostate cancer education materials: applying a standardized assessment tool to currently available materials.

PubMed

Weintraub, Debra; Maliski, Sally L; Fink, Arlene; Choe, Sarah; Litwin, Mark S

2004-11-01

Written educational materials serve as important teaching instruments for prostate cancer patients and their families. However, they must be understandable for their intended audiences. We examined prostate cancer brochures and pamphlets using the Suitability Assessment of Materials (SAM) instrument for the materials' overall suitability, readability, and cultural appropriateness. These factors are crucial to ensure that patients are able to understand and relate to the information. Our evaluation of 29 materials demonstrated that the majority, 22 (75.8%), scored "adequate" for their overall suitability. However, 26 materials (90%) scored "not suitable" for their reading grade level, while 55% of the materials could not be rated on cultural appropriateness because of lack of cues about the intended audience. Also, many of the materials scored poorly on content, graphics, self-efficacy, and learning motivation and stimulation. Most of the materials did well with typography and layout. Overall, the findings point to the need to carefully assess written materials used for multicultural audiences with low reading ability.

Metastatic castration-resistant prostate cancer: time for innovation.

PubMed

Tucci, Marcello; Scagliotti, Giorgio Vittorio; Vignani, Francesca

2015-01-01

Androgen deprivation is the mainstay of advanced prostate cancer treatment. Despite initial responses, almost all patients progress to castration-resistant prostate cancer (CRPC). The understanding of the biology of CRPC and the evidence that CRPC still remains driven by androgen receptor signaling led to the discovery of new therapeutic targets. In the last few years, large Phase III trials showed improvements in survival and outcomes and led to the approval of a CYP17 inhibitor (abiraterone), an androgen receptor antagonist (enzalutamide), the taxane cabazitaxel, an α-emitter (radium-223), the bone resorption-targeting drug denosumab and an immunotherapy (sipuleucel-T). This article describes the molecular mechanisms underlying castration resistance, discusses recent and ongoing trials and offers some insights into identifying the best sequence of new drugs.

The Voice of the Patient Methodology: A Novel Mixed-Methods Approach to Identifying Treatment Goals for Men with Prostate Cancer.

PubMed

Saigal, Christopher S; Lambrechts, Sylvia I; Seenu Srinivasan, V; Dahan, Ely

2017-06-01

Many guidelines advocate the use of shared decision making for men with newly diagnosed prostate cancer. Decision aids can facilitate the process of shared decision making. Implicit in this approach is the idea that physicians understand which elements of treatment matter to patients. Little formal work exists to guide physicians or developers of decision aids in identifying these attributes. We use a mixed-methods technique adapted from marketing science, the 'Voice of the Patient', to describe and identify treatment elements of value for men with localized prostate cancer. We conducted semi-structured interviews with 30 men treated for prostate cancer in the urology clinic of the West Los Angeles Veteran Affairs Medical Center. We used a qualitative analysis to generate themes in patient narratives, and a quantitative approach, agglomerative hierarchical clustering, to identify attributes of treatment that were most relevant to patients making decisions about prostate cancer. We identified five 'traditional' prostate cancer treatment attributes: sexual dysfunction, bowel problems, urinary problems, lifespan, and others' opinions. We further identified two novel treatment attributes: a treatment's ability to validate a sense of proactivity and the need for an incision (separate from risks of surgery). Application of a successful marketing technique, the 'Voice of the Customer', in a clinical setting elicits non-obvious attributes that highlight unique patient decision-making concerns. Use of this method in the development of decision aids may result in more effective decision support.

Development of glycan specific lectin based immunoassay for detection of prostate specific antigen.

PubMed

Bhanushali, Paresh B; Badgujar, Shamkant B; Tripathi, Mukesh M; Gupta, Sanjeev; Murthy, Vedang; Krishnasastry, Musti V; Puri, Chander P

2016-05-01

We describe an analytical approach for the detection and verification of glycosylation patterns of prostate specific antigen (PSA), a key biomarker currently used for understanding the onset and prognosis of prostate cancer. PSA has been purified from the human seminal plasma and total PSA from prostate cancer sera. PSA is a monomeric glycoprotein with an apparent molecular mass 28040.467 Da, which exhibits a characteristic protease activity against casein and gelatin. Its optimal protease activity is centered on neutral pH. Peptide mass fingerprint analysis of the purified PSA has yielded peptides that partially match with known database sequences (Uniprot ID P07288). Tryptic digestion profile of isolated PSA, infer the exclusive nature of PSA and may be additive molecule in the dictionary of seminal proteins. Surface plasmon resonance and lectin immunoassay revealed direct interaction between a newly developed anti-PSA monoclonal antibody (C4E6) and PSA. A lectin based immunoassay is reported here which was achieved with the C4E6 anti-PSA antibody and biotinylated plant lectins. This investigation provides an alternative method to isolate and quantify PSA with altered glycosylation which might be seen in the prostate cancer and developing a lectin based immunoassay to detect PSA in serum of prostate cancer patients. Copyright © 2016 Elsevier B.V. All rights reserved.

The ubiquitin ligase TRIM25 targets ERG for degradation in prostate cancer.

PubMed

Wang, Shan; Kollipara, Rahul K; Humphries, Caroline G; Ma, Shi-Hong; Hutchinson, Ryan; Li, Rui; Siddiqui, Javed; Tomlins, Scott A; Raj, Ganesh V; Kittler, Ralf

2016-10-04

Ets related gene (ERG) is a transcription factor that is overexpressed in 40% of prostate tumors due to a gene fusion between ERG and TMPRSS2. Because ERG functions as a driver of prostate carcinogenesis, understanding the mechanisms that influence its turnover may provide new molecular handles to target the protein. Previously, we found that ERG undergoes ubiquitination and then is deubiquitinated by USP9X in prostate cancer cells to prevent its proteasomal degradation. Here, we identify Tripartite motif-containing protein 25 (TRIM25) as the E3 ubiquitin ligase that ubiquitinates the protein prior to its degradation. TRIM25 binds full-length ERG, and it also binds the N-terminally truncated variants of ERG that are expressed in tumors with TMPRSS2-ERG fusions. We demonstrate that TRIM25 polyubiquitinates ERG in vitro and that inactivation of TRIM25 resulted in reduced polyubiquitination and stabilization of ERG. TRIM25 mRNA and protein expression was increased in ERG rearrangement-positive prostate cancer specimens, and we provide evidence that ERG upregulates TRIM25 expression. Thus, overexpression of ERG in prostate cancer may cause an increase in TRIM25 activity, which is mitigated by the expression of the deubiquitinase USP9X, which is required to stabilize ERG.

The ubiquitin ligase TRIM25 targets ERG for degradation in prostate cancer

PubMed Central

Wang, Shan; Kollipara, Rahul K.; Humphries, Caroline G.; Ma, Shi-Hong; Hutchinson, Ryan; Li, Rui; Siddiqui, Javed; Tomlins, Scott A.; Raj, Ganesh V.; Kittler, Ralf

2016-01-01

Ets related gene (ERG) is a transcription factor that is overexpressed in 40% of prostate tumors due to a gene fusion between ERG and TMPRSS2. Because ERG functions as a driver of prostate carcinogenesis, understanding the mechanisms that influence its turnover may provide new molecular handles to target the protein. Previously, we found that ERG undergoes ubiquitination and then is deubiquitinated by USP9X in prostate cancer cells to prevent its proteasomal degradation. Here, we identify Tripartite motif-containing protein 25 (TRIM25) as the E3 ubiquitin ligase that ubiquitinates the protein prior to its degradation. TRIM25 binds full-length ERG, and it also binds the N-terminally truncated variants of ERG that are expressed in tumors with TMPRSS2-ERG fusions. We demonstrate that TRIM25 polyubiquitinates ERG in vitro and that inactivation of TRIM25 resulted in reduced polyubiquitination and stabilization of ERG. TRIM25 mRNA and protein expression was increased in ERG rearrangement-positive prostate cancer specimens, and we provide evidence that ERG upregulates TRIM25 expression. Thus, overexpression of ERG in prostate cancer may cause an increase in TRIM25 activity, which is mitigated by the expression of the deubiquitinase USP9X, which is required to stabilize ERG. PMID:27626314

[Lutetium-177-PSMA radioligand therapy : Consensus within the framework of GKV-funded care between the university hospitals in Aachen, Bonn, Düsseldorf, Essen, and Cologne and the MDK Nordrhein].

PubMed

Ahmadzadehfar, H; Albers, P; Bockisch, A; Boegemann, M; Böhme, C; Burchert, W; Dietlein, M; Drzezga, A; Fabry, U; Feldmann, G; Heidenreich, A; Heinzel, A; Herrmann, K; Heyll, A; Höhling, C; Kreuzer, C; Laufer, D; Mengel, R; Mottaghy, F M; Müller, H-W; Müller, S C; Ost, E; Rahbar, K; Reifenhäuser, W; Schäfers, M; Schlenkhoff, C; Schmidt, M; Schmidt-Wolf, I; Wildenhain, C; Zimmer, B; Essler, M

2018-06-01

In the last 3 years, Lutetium-177 prostate-specific membrane antigen radioligand therapy (Lu-177-PSMA-RLT) has received increasing attention in nuclear medicine as a new form of treatment for castration-resistant metastatic prostate cancer. This therapy combines the radionuclide Lutetium-177, which has been therapeutically used in nuclear medicine for many years, with a molecular target of the transmembrane prostate-specific membrane antigen expressed by prostate cancer cells. Since there are no prospective randomized studies on Lu-177-PSMA-RLT and the question of reimbursement has repeatedly been the subject of review by the MDK Nordrhein (Medischenische Dienst der Krankenversicherung), there was a desire because of the increasing number of patients being treated to clarify under which circumstances Lu-177-PSMA-RLT can be reimbursed by German statutory health insurance. The goals of this article are to help treating physicians understand how this new therapy option works, to integrate it in the overall therapy concept for castration-resistant metastatic prostate cancer, and, above all, to use Lu-177-PSMA-RLT-based on the current data-at the right place in the therapy sequence of castration-resistant metastatic prostate cancer.

[Prostate specific antigen and NF-kB in prostatic disease: relation with malignancy].

PubMed

Cansino, J R; Vera, R; Rodríguez de Bethencourt, F; Bouraoui, Y; Rodríguez, G; Prieto, A; de la Peña, J; Paniagua, R; Royuela, M

2011-01-01

NF-kB (p50/p65) is a transcription factor involved in TNF-α-induced cell death resistance by promoting several antiapoptotic genes. We intend to relate the expression of NF-kB (p50 and p65) with serum levels of prostate-specific antigen (PSA), both in normal males and in those with pathologic conditions of the prostate. this study was carried out in 5 normal, 24 benign prostatic hyperplastic (BPH) and 19 patients with prostate cancer (PC). Immunohistochemical and Western blot analyses were performed on tissue and serum PSA was assayed by PSA DPC Immulite assays (Diagnostics Products Corporation, Los Angeles, CA). in controls, p65 NF-kB was not found and p50 was scantly detected in 60% normal samples in the cytoplasm of epithelial cells. Both p50 and p65 were expressed in 62.5% of the samples with BPH and in 63.2% of those with PC. Both increased its frequency of expression with higher PSA serum levels. Activation of NF-kB revealed by its nuclear translocation in prostate cancer could be related to cancer progression and elevated seric PSA levels. A better understanding of the biologic mechanism by which circulating PSA levels increase and its relation with NF-kB expression is needed. Possibly, NF-kB blockage could be used as a therapeutic target to counteract proliferation in prostate cancer. Copyright © 2010 AEU. Published by Elsevier Espana. All rights reserved.

Hypofractionated Radiation Therapy in Treating Participants With Prostate Cancer High-Risk Features Following Radical Prostatectomy

ClinicalTrials.gov

2018-06-25

Prostate Adenocarcinoma; PSA Level Less Than Two; Stage IIB Prostate Cancer AJCC v8; Stage III Prostate Cancer AJCC v8; Stage IIIA Prostate Cancer AJCC v8; Stage IIIB Prostate Cancer AJCC v8; Stage IIIC Prostate Cancer AJCC v8

Decision Aids in Improving Knowledge in Patients With Newly Diagnosed Prostate Cancer

ClinicalTrials.gov

2018-06-08

Stage II Prostate Cancer; Stage IIA Prostate Cancer; Stage IIB Prostate Cancer; Stage III Prostate Cancer; Stage I Prostate Cancer; PSA Level Five to Ten; PSA Level Less Than Five; PSA Level Ten to Fifty

Negative information seeking experiences of long-term prostate cancer survivors

PubMed Central

Bernat, Jennifer K.; Skolarus, Ted A.; Hawley, Sarah T.; Haggstrom, David A.; Darwish-Yassine, May; Wittmann, Daniela A.

2016-01-01

Purpose Many prostate cancer survivors have lasting symptoms and disease-related concerns for which they seek information. To understand survivors’ information seeking experiences, we examined the topics of their information searches, their overall perceptions of the search, and perceptions of their health information seeking self-efficacy (i.e., confidence in their ability to obtain information). We hypothesized that negative search experiences and lower health information seeking self-efficacy would be associated with certain survivor characteristics such as non-white race, low income, and less education. Methods This was a retrospective study using data from the Michigan Prostate Cancer Survivor Study (state-based survey of long-term prostate cancer survivor outcomes, N=2,499, response rate = 38%). Participants recalled their last search for information and reported the topics and overall experience. We conducted multivariable regression to examine the association between survivor characteristics and the information-seeking experience. Results Nearly a third (31.7%) of prostate cancer survivors (median age of 76 years and 9 years since diagnosis) reported having negative information seeking experiences when looking for information. However, only 13.4% reported having low health information seeking self-efficacy. Lower income and less education were both significantly associated with negative information seeking experiences. Conclusions Our findings suggest that many long-term prostate cancer survivors have negative experiences when searching for information, and lower income and less education were survivor factors related to negative information seeking experiences. Implications for cancer survivors We advocate for ongoing, information needs assessment at the point-of-care as the survivorship experience progresses to assess and potentially improve survivors’ quality of life. PMID:27229868

δ-Tocopherol inhibits receptor tyrosine kinase-induced AKT activation in prostate cancer cells.

PubMed

Wang, Hong; Hong, Jungil; Yang, Chung S

2016-11-01

The cancer preventive activity of vitamin E is suggested by epidemiological studies and supported by animal studies with vitamin E forms, γ-tocopherol and δ-tocopherol (δ-T). Several recent large-scale cancer prevention trials with high dose of α-tocopherol, however, yielded disappointing results. Whether vitamin E prevents or promotes cancer is a serious concern. A better understanding of the molecular mechanisms of action of the different forms of tocopherols would enhance our understanding of this topic. In this study, we demonstrated that δ-T was the most effective tocopherol form in inhibiting prostate cancer cell growth, by inducing cell cycle arrest and apoptosis. By profiling the effects of δ-T on the cell signaling using the phospho-kinase array, we found that the most inhibited target was the phosphorylation of AKT on T308. Further study on the activation of AKT by EGFR and IGFR revealed that δ-T attenuated the EGF/IGF-induced activation of AKT (via the phosphorylation of AKT on T308 induced by the activation of PIK3). Expression of dominant active PIK3 and AKT in prostate cancer cell line DU145 in which PIK3, AKT, and PTEN are wild type caused the cells to be reflectory to the inhibition of δ-T, supporting that δ-T inhibits the PIK3-mediated activation of AKT. Our data also suggest that δ-T interferes with the EGF-induced EGFR internalization, which leads to the inhibition of the receptor tyrosine kinase-dependent activation of AKT. In summary, our results revealed a novel mechanism of δ-T in inhibiting prostate cancer cell growth, supporting the cancer preventive activity δ-T. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

The Relationship Between Education and Prostate-Specific Antigen Testing Among Urban African American Medicare Beneficiaries

PubMed Central

Pollack, Craig Evan; Garza, Mary A.; Yeh, Hsin-Chieh; Markakis, Diane; Phelan-Emrick, Darcy F.; Wenzel, Jennifer; Shapiro, Gary R.; Bone, Lee; Johnson, Lawrence

2017-01-01

Purpose We examined the association between socioeconomic status (SES) and prostate-specific antigen (PSA) cancer screening among older African American men. Methods We analyzed baseline data from a sample of 485 community-dwelling African American men who participated in the Cancer Prevention and Treatment Demonstration Trial. The outcome was receipt of PSA screening within the past year. SES was measured using income and educational attainment. Sequential multivariate logistic regression models were performed to study whether health care access, patient–provider relationship, and cancer fatalism mediated the relationship between SES and PSA screening. Results Higher educational attainment was significantly associated with higher odds of PSA screening in the past year (odds ratio (OR) 2.08 for college graduate compared to less than high school graduate, 95 % confidence interval (CI) 1.03–4.24); income was not. Health care access and patient–provider communication did not alter the relationship between education and screening; however, beliefs regarding cancer fatalism partially mediated the observed relationship. Conclusion Rates of prostate cancer screening among African American men vary by level of educational attainment; beliefs concerning cancer fatalism help explain this gradient. Understanding the determinants of cancer fatalism is a critical next step in building interventions that seek to ensure equitable access to prostate cancer screening. PMID:26863336

The Relationship Between Education and Prostate-Specific Antigen Testing Among Urban African American Medicare Beneficiaries.

PubMed

Hararah, Mohammad Khalid; Pollack, Craig Evan; Garza, Mary A; Yeh, Hsin-Chieh; Markakis, Diane; Phelan-Emrick, Darcy F; Wenzel, Jennifer; Shapiro, Gary R; Bone, Lee; Johnson, Lawrence; Ford, Jean G

2015-06-01

We examined the association between socioeconomic status (SES) and prostate-specific antigen (PSA) cancer screening among older African American men. We analyzed baseline data from a sample of 485 community-dwelling African American men who participated in the Cancer Prevention and Treatment Demonstration Trial. The outcome was receipt of PSA screening within the past year. SES was measured using income and educational attainment. Sequential multivariate logistic regression models were performed to study whether health care access, patient-provider relationship, and cancer fatalism mediated the relationship between SES and PSA screening. Higher educational attainment was significantly associated with higher odds of PSA screening in the past year (odds ratio (OR) 2.08 for college graduate compared to less than high school graduate, 95 % confidence interval (CI) 1.03-4.24); income was not. Health care access and patient-provider communication did not alter the relationship between education and screening; however, beliefs regarding cancer fatalism partially mediated the observed relationship. Rates of prostate cancer screening among African American men vary by level of educational attainment; beliefs concerning cancer fatalism help explain this gradient. Understanding the determinants of cancer fatalism is a critical next step in building interventions that seek to ensure equitable access to prostate cancer screening.

The HOXB13 G84E Mutation Is Associated with an Increased Risk for Prostate Cancer and Other Malignancies.

PubMed

Beebe-Dimmer, Jennifer L; Hathcock, Matthew; Yee, Cecilia; Okoth, Linda A; Ewing, Charles M; Isaacs, William B; Cooney, Kathleen A; Thibodeau, Stephen N

2015-09-01

A rare nonconservative substitution (G84E) in the HOXB13 gene has been shown to be associated with risk of prostate cancer. DNA samples from male patients included in the Mayo Clinic Biobank (MCB) were genotyped to determine the frequency of the G84E mutation and its association with various cancers. Subjects were genotyped using a custom TaqMan (Applied Biosystems) assay for G84E (rs138213197). In addition to donating a blood specimen, all MCB participants completed a baseline questionnaire to collect information on medical history and family history of cancer. Forty-nine of 9,012 male patients were carriers of G84E (0.5%). Thirty-one percent (n = 2,595) of participants had been diagnosed with cancer, including 51.1% of G84E carriers compared with just 30.6% of noncarriers (P = 0.004). G84E was most frequently observed among men with prostate cancer compared with men without cancer (P < 0.0001). However, the mutation was also more commonly observed in men with bladder cancer (P = 0.06) and leukemia (P = 0.01). G84E carriers were more likely to have a positive family history of prostate cancer in a first-degree relative compared to noncarriers (36.2% vs. 16.0%, P = 0.0003). Our study confirms the association between the HOXB13 G84E variant and prostate cancer and suggests a novel association between G84E and leukemia and a suggestive association with bladder cancer. Future investigation is warranted to confirm these associations in order to improve our understanding of the role of germline HOXB13 mutations in human cancer. The associations between HOXB13 and prostate, leukemia, and bladder suggest that this gene is important in carcinogenesis. ©2015 American Association for Cancer Research.

Identification of HLA-DRB1*1501-restricted T-cell epitopes from human prostatic acid phosphatase.

PubMed

Klyushnenkova, Elena N; Kouiavskaia, Diana V; Kodak, James A; Vandenbark, Arthur A; Alexander, Richard B

2007-07-01

The crucial role of CD4 T-cells in anti-tumor immune response is widely recognized, yet the identification of HLA class II-restricted epitopes derived from tumor antigens has lagged behind compared to class I epitopes. This is particularly true for prostate cancer. Based on the hypothesis that successful cancer immunotherapy will likely resemble autoimmunity, we searched for the CD4 T-cell epitopes derived from prostatic proteins that are restricted by human leukocyte antigen (HLA)-DRB1*1501, an allele associated with granulomatous prostatitis (GP), a disease that may have an autoimmune etiology. One of the antigens implicated in the development of autoimmunity in the prostate is prostatic acid phosphatase (PAP), which is also considered a promising target for prostate cancer immunotherapy. We immunized transgenic (tg) mice engineered to express HLA-DRB1*1501 with human PAP. A library of overlapping 20-mer peptides spanning the entire human PAP sequence was screened in vitro for T-cell recognition by proliferative and interferon (IFN)-gamma enzyme-linked immunosorbent spot (ELISPOT) assays. We identified two 20-mer peptides, PAP (133-152), and PAP (173-192), that were immunogenic and naturally processed from whole PAP in HLA-DRB1*1501 tg mice. These peptides were also capable of stimulating CD4 T lymphocytes from HLA-DRB1*1501-positive patients with GP and normal donors. These peptides can be used for the design of a new generation of peptide-based vaccines against prostate cancer. The study can also be helpful in understanding the role of autoimmunity in the development of some forms of chronic prostatitis.

Commentary on "the E3 ubiquitin ligase Siah2 contributes to castration-resistant prostate cancer by regulation of androgen receptor transcriptional activity." Qi J, Tripathi M, Mishra R, Sahgal N, Fazli L, Ettinger S, Placzek WJ, Claps G, Chung LW, Bowtell D, Gleave M, Bhowmick N, Ronai ZA, Signal Transduction Program, Cancer Center, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA.: Cancer Cell 2013;23(6):332-46.

PubMed

Olumi, Aria F

2014-02-01

Understanding the mechanism underlying the regulation of the androgen receptor (AR), a central player in the development of castration-resistant prostate cancer (CRPC), holds promise for overcoming the challenge of treating CRPC. We demonstrate that the ubiquitin ligase Siah2 targets a select pool of NCOR1-bound, transcriptionally-inactive AR for ubiquitin-dependent degradation, thereby promoting expression of select AR target genes implicated in lipid metabolism, cell motility, and proliferation. Siah2 is required for prostate cancer cell growth under androgen-deprivation conditions in vitro and in vivo, and Siah2 inhibition promotes prostate cancer regression upon castration. Notably, Siah2 expression is markedly increased in human CRPCs. Collectively, we find that selective regulation of AR transcriptional activity by the ubiquitin ligase Siah2 is important for CRPC development. Copyright © 2014 Elsevier Inc. All rights reserved.

Magnetic Resonance Spectroscopy (MRS) of Prostatic Fluids for Early Detection of Prostate Cancer

DTIC Science & Technology

2005-10-01

measured using external 1H-NMRS coils, increasing the practicality of the metabonomic approach. In conclusion, the absolute concentrations of the...Lindon, J.C., and Holmes, E. “ Metabonomics ”: understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate

Health behaviour models and patient preferences regarding nutrition and physical activity after breast or prostate cancer diagnosis.

PubMed

Green, H J; Steinnagel, G; Morris, C; Laakso, E L

2014-09-01

This study aimed to improve understanding of prostate and breast cancer survivors' physical activity and nutrition and the association of these behaviours with two models. The first model, the Commonsense Self-Regulation Model (CSM), addresses cognitive and emotional perceptions of illness whereas the Transtheoretical Model (TTM) focuses on stage of readiness to engage in a behaviour. Participants who had been diagnosed with either breast (n = 145) or prostate cancer (n = 92) completed measures of demographic and health information, illness representations, stage of change, self-efficacy and preferences regarding health behaviour interventions. Health behaviours in the past seven days were measured via the International Physical Activity Questionnaire and concordance with national dietary guidelines. As hypothesised, TTM variables (stage of change and self-efficacy) demonstrated independent associations with physical activity and nutrition in regression analyses. CSM variables were not independently associated with absolute levels of health behaviours but both TTM and CSM variables were independently associated with self-reported changes in physical activity and nutrition following prostate or breast cancer diagnosis. Many participants reported high interest in receiving lifestyle interventions, particularly soon after diagnosis. Results supported application of the TTM and CSM models for strengthening behaviour change intentions and actions in breast and prostate cancer survivors. © 2014 John Wiley & Sons Ltd.

Establishing Prostate Cancer Patient Derived Xenografts: Lessons Learned From Older Studies

PubMed Central

Russell, Pamela J; Russell, Peter; Rudduck, Christina; Tse, Brian W-C; Williams, Elizabeth D; Raghavan, Derek

2015-01-01

Background Understanding the progression of prostate cancer to androgen-independence/castrate resistance and development of preclinical testing models are important for developing new prostate cancer therapies. This report describes studies performed 30 years ago, which demonstrate utility and shortfalls of xenografting to preclinical modeling. Methods We subcutaneously implanted male nude mice with small prostate cancer fragments from transurethral resection of the prostate (TURP) from 29 patients. Successful xenografts were passaged into new host mice. They were characterized using histology, immunohistochemistry for marker expression, flow cytometry for ploidy status, and in some cases by electron microscopy and response to testosterone. Two xenografts were karyotyped by G-banding. Results Tissues from 3/29 donors (10%) gave rise to xenografts that were successfully serially passaged in vivo. Two, (UCRU-PR-1, which subsequently was replaced by a mouse fibrosarcoma, and UCRU-PR-2, which combined epithelial and neuroendocrine features) have been described. UCRU-PR-4 line was a poorly differentiated prostatic adenocarcinoma derived from a patient who had undergone estrogen therapy and bilateral castration after his cancer relapsed. Histologically, this comprised diffusely infiltrating small acinar cell carcinoma with more solid aggregates of poorly differentiated adenocarcinoma. The xenografted line showed histology consistent with a poorly differentiated adenocarcinoma and stained positively for prostatic acid phosphatase (PAcP), epithelial membrane antigen (EMA) and the cytokeratin cocktail, CAM5.2, with weak staining for prostate specific antigen (PSA). The line failed to grow in female nude mice. Castration of three male nude mice after xenograft establishment resulted in cessation of growth in one, growth regression in another and transient growth in another, suggesting that some cells had retained androgen sensitivity. The karyotype (from passage 1) was 43–46, XY, dic(1;12)(p11;p11), der(3)t(3:?5)(q13;q13), -5, inv(7)(p15q35) x2, +add(7)(p13), add(8)(p22), add(11)(p14), add(13)(p11), add(20)(p12), -22, +r4[cp8]. Conclusions Xenografts provide a clinically relevant model of prostate cancer, although establishing serially transplantable prostate cancer patient derived xenografts is challenging and requires rigorous characterization and high quality starting material. Xenografting from advanced prostate cancer is more likely to succeed, as xenografting from well differentiated, localized disease has not been achieved in our experience. Strong translational correlations can be demonstrated between the clinical disease state and the xenograft model. Prostate 75: 628–636, 2015. © The Authors. The Prostate published by Wiley Periodicals, Inc. PMID:25560784

Prostate cancer - resources

MedlinePlus

Resources - prostate cancer ... The following organizations are good resources for information on prostate cancer : American Cancer Society -- www.cancer.org/cancer/prostate-cancer.html National Cancer Institute -- www.cancer.gov/ ...

CYTOCHROME P450 17A1 STRUCTURES WITH PROSTATE CANCER DRUGS ABIRATERONE AND TOK-001

PubMed Central

DeVore, Natasha M.; Scott, Emily E.

2011-01-01

Cytochrome P450 17A1 (P450c17) catalyzes the biosynthesis of androgens in humans1. Since prostate cancer cells proliferate in response to androgen steroids2,3, CYP17A1 inhibition is a new strategy to prevent androgen synthesis and treat lethal metastatic castration-resistant prostate cancer4, but drug development has been hampered by the lack of a CYP17A1 structure. Here we report the only known structures of CYP17A1, which contain either abiraterone, a first-in-class steroidal inhibitor recently approved by the FDA for late-stage prostate cancer5, or TOK-001, another inhibitor in clinical trials4,6. Both bind the heme iron forming a 60° angle above the heme plane, packing against the central I helix with the 3β-OH interacting with N202 in the F helix. Importantly, this binding mode differs substantially from those predicted by homology models or from steroids in other cytochrome P450 enzymes with known structures, with some features more similar to steroid receptors. While the overall CYP17A1 structure provides a rationale for understanding many mutations found in patients with steroidogenic diseases, the active site reveals multiple steric and hydrogen bonding features that will facilitate better understanding of the enzyme’s dual hydroxylase and lyase catalytic capabilities and assist in rational drug design. Specifically, structure-based design is expected to aid development of inhibitors that bind only CYP17A1 and solely inhibit its androgen-generating lyase activity to improve treatment of prostate and other hormone-responsive cancers. PMID:22266943

Prostate cancer targeting motifs: expression of αν β3, neurotensin receptor 1, prostate specific membrane antigen, and prostate stem cell antigen in human prostate cancer cell lines and xenografts.

PubMed

Taylor, Robert M; Severns, Virginia; Brown, David C; Bisoffi, Marco; Sillerud, Laurel O

2012-04-01

Membrane receptors are frequent targets of cancer therapeutic and imaging agents. However, promising in vitro results often do not translate to in vivo clinical applications. To better understand this obstacle, we measured the expression differences in receptor signatures among several human prostate cancer cell lines and xenografts as a function of tumorigenicity. Messenger RNA and protein expression levels for integrin α(ν) β(3), neurotensin receptor 1 (NTSR1), prostate specific membrane antigen (PSMA), and prostate stem cell antigen (PSCA) were measured in LNCaP, C4-2, and PC-3 human prostate cancer cell lines and in murine xenografts using quantitative reverse transcriptase polymerase chain reaction, flow cytometry, and immunohistochemistry. Stable expression patterns were observed for integrin α(ν) and PSMA in all cells and corresponding xenografts. Integrin β(3) mRNA expression was greatly reduced in C4-2 xenografts and greatly elevated in PC-3 xenografts compared with the corresponding cultured cells. NTSR1 mRNA expression was greatly elevated in LNCaP and PC-3 xenografts. PSCA mRNA expression was elevated in C4-2 xenografts when compared with C4-2 cells cultured in vitro. Furthermore, at the protein level, PSCA was re-expressed in all xenografts compared with cells in culture. The regulation of mRNA and protein expression of the cell-surface target proteins α(ν) β(3), NTSR1, PSMA, and PSCA, in prostate cancer cells with different tumorigenic potential, was influenced by factors of the microenvironment, differing between cell cultures and murine xenotransplants. Integrin α(ν) β(3), NTRS1 and PSCA mRNA expression increased with tumorigenic potential, but mRNA expression levels for these proteins do not translate directly to equivalent expression levels of membrane bound protein. Copyright © 2011 Wiley Periodicals, Inc.

Early Light Imaging for Biomedical Applications

DTIC Science & Technology

2000-07-01

such as prostate cancer, breast cancer, cervical cancer, glaucoma , macular degeneration, macular endema, and atherosclerosis plaques. Understanding of...harmonic- generation cross-correlation time gating", Opt. Lett., 16 1019-1021 (1991) 17. K. Yoo, Z. Zang, S. Ahmed , R. Alfano, "Imaging objects hidden

Tweeting About Prostate and Testicular Cancers: Do Twitter Conversations and the 2013 Movember Canada Campaign Objectives Align?

PubMed

Bravo, Caroline A; Hoffman-Goetz, Laurie

2016-06-01

Prostate cancer is the most frequently diagnosed cancer of the reproductive system in men. Mass media campaigns have long been a tool for raising awareness of important health issues and changing health behavior. The Movember campaign was launched in Canada in 2007 with the goal of creating conversations about men's health in order to raise awareness and understanding about prostate cancer. In 2012, testicular cancer was added to the Movember Canada campaign agenda. Social networking sites such as Twitter are popular platforms for conversations in the digital age. Our objective was to determine if the Movember Canada 2013 campaign accomplished the goal of creating conversations about prostate and testicular cancers on the social media platform of Twitter. We conducted a content analysis of 4222 Canadian tweets posted during the November 2013 Movember Canada campaign to investigate whether tweets were health-related or non-health-related and to determine what topics of discussion were present in the tweets. There were significantly fewer health-related (n = 673) than non-health-related (n = 3549) tweets (p < 0.05). Few tweets (0.6 % of all tweets) referenced prostate or testicular cancers. Community engagement activities as well as moustache and grooming references were the most frequent topics in the health-related (10.49 and 1.97 %) and non-health-related (32.83 and 32.76 %) categories, which were significantly different by topic (p < 0.05). Findings from Twitter suggest that the Movember Canada 2013 did not meet the stated campaign objective of creating conversations about men's health and, specifically, about prostate and testicular cancers.

Prostate cancer screening

MedlinePlus

Prostate cancer screening - PSA; Prostate cancer screening - digital rectal exam; Prostate cancer screening - DRE ... level of PSA could mean you have prostate cancer. But other conditions can also cause a high ...

Faith Among Low-Income, African American/Black Men Treated for Prostate Cancer

PubMed Central

Maliski, Sally L.; Connor, RN Sarah E.; Williams, Lindsay; Litwin, Mark S.

2014-01-01

Background Understanding how low-income, uninsured African American/black men use faith to cope with prostate cancer provides a foundation for the design of culturally appropriate interventions to assist underserved men cope with the disease and its treatment. Previous studies have shown spirituality to be a factor related to health and quality of life, but the process by which faith, as a promoter of action, supports coping merits exploration. Objective Our purpose was to describe the use of faith by low-income, uninsured African American/black men in coping with prostate cancer and its treatment and adverse effects. Methods We analyzed data from a qualitative study that used in-depth individual interviews involving 18 African American men ranging in ages from 53 to 81 years. Our analysis used grounded theory techniques. Results Faith was used by African American men to overcome fear and shock engendered by their initial perceptions of cancer. Faith was placed in God, health care providers, self, and family. Men came to see their prostate cancer experience a new beginning that was achieved through purposeful acceptance or resignation. Conclusions Faith was a motivator of and source for action. Faith empowered men to be active participants in their treatment and incorporate treatment outcomes into their lives meaningfully. Implication By understanding faith as a source of empowerment for active participation in care, oncology nurses can use men's faith to facilitate reframing of cancer perceptions and to acknowledge the role of men's higher being as part of the team. Studies are needed to determine if this model is relevant across various beliefs and cultures. PMID:20555257

Nutrigenetics and prostate cancer: 2011 and beyond.

PubMed

Yuan, Yinan; Ferguson, Lynnette R

2011-01-01

Prostate cancer runs in families and shows a clear dietary involvement. Until recently, the key risk gene(s) have proved elusive. We summarise current understandings of nutrient-gene interactions in prostate cancer risk and progression. A MEDLINE-based literature search was conducted. Hypothesis-directed candidate gene approaches provide plausible, albeit statistically weak, nutrient-gene interactions. These are based on early understandings of factors likely to impact on carcinogenesis, including both nutrient and genetic effects on androgen biosynthesis and action, xenobiotic metabolism, DNA damage and DNA repair. Non-hypothesis-directed genome-wide association studies provide much stronger evidence for other genes, not hitherto suspected for involvement. Although only a few of these have been formally tested for dietary associations in well-designed epidemiologic studies, the nature of many of the genes suggests that their activity may be regulated by nutrients. These effects may not only be relevant to prostate cancer susceptibility, but also to disease progression. It will be important to move beyond studying single nucleotide polymorphisms, into more complex chromosomal rearrangements and to epigenetic changes. For future progress, large international cohorts will not only need to provide proof of individual nutrient-gene interactions, but also to relate these to more complex nutrient-gene-gene interactions, as parts of pathways. Bioinformatics and biostatistics will be increasingly important tools in nutrigenetic studies beyond 2011. Copyright © 2011 S. Karger AG, Basel.

sEphB4-HSA Before Surgery in Treating Patients With Bladder Cancer, Prostate Cancer, or Kidney Cancer

ClinicalTrials.gov

2018-06-08

Infiltrating Bladder Urothelial Carcinoma; Recurrent Bladder Carcinoma; Stage I Prostate Cancer; Stage I Renal Cell Cancer; Stage II Bladder Urothelial Carcinoma; Stage II Renal Cell Cancer; Stage IIA Prostate Cancer; Stage IIB Prostate Cancer; Stage III Prostate Cancer; Stage III Renal Cell Cancer

A Double Blind, Randomized, Neoadjuvant Study of the Tissue effects of POMx Pills in Men with Prostate Cancer Prior to Radical Prostatectomy

PubMed Central

Freedland, Stephen J.; Carducci, Michael; Kroeger, Nils; Partin, Alan; Rao, Jian-yu; Jin, Yusheng; Kerkoutian, Susan; Wu, Hong; Li, Yunfeng; Creel, Patricia; Mundy, Kelly; Gurganus, Robin; Fedor, Helen; King, Serina A.; Zhang, Yanjun; Heber, David; Pantuck, Allan J.

2013-01-01

Pomegranates slow prostate cancer xenograft growth and prolong PSA doubling times in single-arm human studies. Pomegranates’ effects on human prostate tissue are understudied. We hypothesized orally administered pomegranate extract (POMx; PomWonderful, Los Angeles, CA) would lower tissue 8-hydroxy-2-deoxyguanosine (8-OHdG), an oxidative stress biomarker. 70 men were randomized to 2 tablets POMx or placebo daily up to 4 weeks prior to radical prostatectomy. Tissue was analyzed for intra-prostatic Urolithin A, a pomegranate metabolite, benign and malignant 8-OHdG, and cancer pS6 kinase, NFκB, and Ki67. Primary end-point was differences in 8-OHdG powered to detect 30% reduction. POMx was associated with 16% lower benign tissue 8-OHdG (p=0.095), which was not statistically significant. POMx was well-tolerated with no treatment-related withdrawals. There were no differences in baseline clinicopathological features between arms. Urolithin A was detected in 21/33 patient in the POMx group vs. 12/35 in the placebo group (p=0.031). Cancer pS6 kinase, NFκB, Ki67, and serum PSA changes were similar between arms. POMx prior to surgery results in pomegranate metabolite accumulation in prostate tissues. Our primary end-point in this modest-sized short-term trial was negative. Future larger longer studies are needed to more definitely test whether POMx reduces prostate oxidative stress as well as further animal testing to better understand the multiple mechanisms through which POMx may alter prostate cancer biology. PMID:23985577

Obesity and prostate cancer detection: insights from three national surveys.

PubMed

Parekh, Niyati; Lin, Yong; Dipaola, Robert S; Marcella, Stephen; Lu-Yao, Grace

2010-09-01

Previous studies suggest that obesity is associated with higher prostate cancer progression and mortality despite an association with lower prostate cancer incidence. This study aims to better understand these apparently inconsistent relationships among obese men by combining evidence from 3 nationally representative cross-sectional surveys. We evaluated relationships between obesity and 1) testosterone concentrations in the Third National Health and Nutrition Examination Survey (NHANES III; n=845); 2) prostate-specific antigen (PSA) in NHANES 2001-2004 (n=2458); and 3) prostate biopsy rates in the National Health Interview Survey (NHIS 2000; n=4789) population. Mean testosterone, PSA concentrations, and biopsy rates were computed for Body Mass Index (BMI) categories. Testosterone concentrations were inversely associated with obesity (P-trend <.0001) in NHANES III. In NHANES 2001-2004, obese (BMI >35) versus lean (BMI <25) men were less likely to have PSA concentrations that reached the biopsy threshold of >4 ng/mL (3% vs 8%; P <.0001). Among NHIS participants, all BMI groups had similar rates of PSA testing (P=.24). However, among men who had PSA tests, 11% of men with BMI >30 versus 16% with BMI <25, achieved a PSA threshold of 4 ng/mL; P=.01. Furthermore, biopsy rates were lower among men with BMI >30 versus BMI <25 in NHIS participants (4.6% vs 5.8%; P=.05). Obesity was associated with lower PSA-driven biopsy rates. These data support further studies to test the hypothesis that obesity affects prostate cancer detection independent of prostate cancer risk by decreasing the PSA-driven biopsy rates.

Prostate Cancer Stem Cells: Viewing Signaling Cascades at a Finer Resolution.

PubMed

Lin, Xiukun; Farooqi, Ammad Ahmad; Qureshi, Muhammad Zahid; Romero, Mirna Azalea; Tabassum, Sobia; Ismail, Muhammad

2016-06-01

It is becoming characteristically more understandable that within tumor cells, there lies a sub-population of tumor cells with "stem cell" like properties and remarkable ability of self-renewal. Many features of these self-renewing cells are comparable with normal stem cells and are termed as "cancer stem cells". Accumulating experimentally verified data has started to scratch the surface of spatio-temporally dysregulated intracellular signaling cascades in the biology of prostate cancer stem cells. We partition this multicomponent review into how different signaling cascades operate in cancer stem cells and how bioactive ingredients isolated from natural sources may modulate signaling network.

Deep sequencing reveals distinct patterns of DNA methylation in prostate cancer.

PubMed

Kim, Jung H; Dhanasekaran, Saravana M; Prensner, John R; Cao, Xuhong; Robinson, Daniel; Kalyana-Sundaram, Shanker; Huang, Christina; Shankar, Sunita; Jing, Xiaojun; Iyer, Matthew; Hu, Ming; Sam, Lee; Grasso, Catherine; Maher, Christopher A; Palanisamy, Nallasivam; Mehra, Rohit; Kominsky, Hal D; Siddiqui, Javed; Yu, Jindan; Qin, Zhaohui S; Chinnaiyan, Arul M

2011-07-01

Beginning with precursor lesions, aberrant DNA methylation marks the entire spectrum of prostate cancer progression. We mapped the global DNA methylation patterns in select prostate tissues and cell lines using MethylPlex-next-generation sequencing (M-NGS). Hidden Markov model-based next-generation sequence analysis identified ∼68,000 methylated regions per sample. While global CpG island (CGI) methylation was not differential between benign adjacent and cancer samples, overall promoter CGI methylation significantly increased from ~12.6% in benign samples to 19.3% and 21.8% in localized and metastatic cancer tissues, respectively (P-value < 2 × 10(-16)). We found distinct patterns of promoter methylation around transcription start sites, where methylation occurred not only on the CGIs, but also on flanking regions and CGI sparse promoters. Among the 6691 methylated promoters in prostate tissues, 2481 differentially methylated regions (DMRs) are cancer-specific, including numerous novel DMRs. A novel cancer-specific DMR in the WFDC2 promoter showed frequent methylation in cancer (17/22 tissues, 6/6 cell lines), but not in the benign tissues (0/10) and normal PrEC cells. Integration of LNCaP DNA methylation and H3K4me3 data suggested an epigenetic mechanism for alternate transcription start site utilization, and these modifications segregated into distinct regions when present on the same promoter. Finally, we observed differences in repeat element methylation, particularly LINE-1, between ERG gene fusion-positive and -negative cancers, and we confirmed this observation using pyrosequencing on a tissue panel. This comprehensive methylome map will further our understanding of epigenetic regulation in prostate cancer progression.

Emerging Roles of Human Prostatic Acid Phosphatase

PubMed Central

Kong, Hoon Young; Byun, Jonghoe

2013-01-01

Prostate cancer is one of the most prevalent non-skin related cancers. It is the second leading cause of cancer deaths among males in most Western countries. If prostate cancer is diagnosed in its early stages, there is a higher probability that it will be completely cured. Prostatic acid phosphatase (PAP) is a non-specific phosphomonoesterase synthesized in prostate epithelial cells and its level proportionally increases with prostate cancer progression. PAP was the biochemical diagnostic mainstay for prostate cancer until the introduction of prostate-specific antigen (PSA) which improved the detection of early-stage prostate cancer and largely displaced PAP. Recently, however, there is a renewed interest in PAP because of its usefulness in prognosticating intermediate to high-risk prostate cancers and its success in the immunotherapy of prostate cancer. Although PAP is believed to be a key regulator of prostate cell growth, its exact role in normal prostate as well as detailed molecular mechanism of PAP regulation is still unclear. Here, many different aspects of PAP in prostate cancer are revisited and its emerging roles in other environment are discussed. PMID:24009853

All-Cause Mortality for Life Insurance Applicants with a History of Prostate Cancer.

PubMed

Freitas, Stephen A; MacKenzie, Ross; Wylde, David N; Roudebush, Bradley T; Bergstrom, Richard L; Holowaty, J Carl; Beckman, Margaret; Rigatti, Steven J; Gill, Stacy

2017-01-01

- To determine the all-cause mortality of life insurance applicants diagnosed with prostate cancer currently or at some time in the past. - Prostate cancer is common and a frequent cause of cancer death. Both the frequency of prostate cancer in men and its propensity for causing premature mortality require insurance company medical directors and underwriters to have a good understanding of prostate cancer-related mortality trends, patterns, and outcomes in the insured population. - Life insurance applicants with reported prostate cancer were extracted from data covering United States residents between November 2007 and November 2014. Information about these applicants was matched to the Social Security Death Master (SSDMF) file for deaths occurring from 2007 to 2011 and to another commercially available death source file (Other Death Source, ODS) for deaths occurring from 2007 to 2014 to determine vital status. Actual to Expected (A/E) mortality ratios were calculated using the Society of Actuaries 2015 Valuation Basic Table (2015VBT), select and ultimate table (age last birthday) and the 2013 US population as expected mortality ratios. All expected bases were not smoker distinct. - The study covered applicants between the ages of 45 and 75 and had approximately 405,000 person-years of exposure. Older aged applicants had a lower mortality ratio than those who were younger. Applicants 45 to 54 had the highest mortality ratios in the first year after diagnosis which steadily decreased in years 6 to 10 with an increase in the mortality ratio for those over 10 years from diagnosis. Relative mortality rate was close to unity for those with localized cancer across all age groups. The mortality ratio was 2 to 4 times greater for those with cancer in 1 positive node, and much greater with 3 positive nodes. For each time-from-diagnosis category, the relative mortality ratios compared to age were highest in the 45-54 age group. The A/E mortality ratios based on the 2015VBT were consistently 3 to 4 times that of the mortality ratios based on the 2013 US population. - The mortality patterns of insurance applicants with prostate cancer were similar to that observed in individuals with prostate cancer in the general population. Applicant age, time to diagnosis and cancer severity were the most significant variables to predict mortality.

Establishing prostate cancer patient derived xenografts: lessons learned from older studies.

PubMed

Russell, Pamela J; Russell, Peter; Rudduck, Christina; Tse, Brian W C; Williams, Elizabeth D; Raghavan, Derek

2015-05-01

Understanding the progression of prostate cancer to androgen-independence/castrate resistance and development of preclinical testing models are important for developing new prostate cancer therapies. This report describes studies performed 30 years ago, which demonstrate utility and shortfalls of xenografting to preclinical modeling. We subcutaneously implanted male nude mice with small prostate cancer fragments from transurethral resection of the prostate (TURP) from 29 patients. Successful xenografts were passaged into new host mice. They were characterized using histology, immunohistochemistry for marker expression, flow cytometry for ploidy status, and in some cases by electron microscopy and response to testosterone. Two xenografts were karyotyped by G-banding. Tissues from 3/29 donors (10%) gave rise to xenografts that were successfully serially passaged in vivo. Two, (UCRU-PR-1, which subsequently was replaced by a mouse fibrosarcoma, and UCRU-PR-2, which combined epithelial and neuroendocrine features) have been described. UCRU-PR-4 line was a poorly differentiated prostatic adenocarcinoma derived from a patient who had undergone estrogen therapy and bilateral castration after his cancer relapsed. Histologically, this comprised diffusely infiltrating small acinar cell carcinoma with more solid aggregates of poorly differentiated adenocarcinoma. The xenografted line showed histology consistent with a poorly differentiated adenocarcinoma and stained positively for prostatic acid phosphatase (PAcP), epithelial membrane antigen (EMA) and the cytokeratin cocktail, CAM5.2, with weak staining for prostate specific antigen (PSA). The line failed to grow in female nude mice. Castration of three male nude mice after xenograft establishment resulted in cessation of growth in one, growth regression in another and transient growth in another, suggesting that some cells had retained androgen sensitivity. The karyotype (from passage 1) was 43-46, XY, dic(1;12)(p11;p11), der(3)t(3:?5)(q13;q13), -5, inv(7)(p15q35) x2, +add(7)(p13), add(8)(p22), add(11)(p14), add(13)(p11), add(20)(p12), -22, +r4[cp8]. Xenografts provide a clinically relevant model of prostate cancer, although establishing serially transplantable prostate cancer patient derived xenografts is challenging and requires rigorous characterization and high quality starting material. Xenografting from advanced prostate cancer is more likely to succeed, as xenografting from well differentiated, localized disease has not been achieved in our experience. Strong translational correlations can be demonstrated between the clinical disease state and the xenograft model. © 2015 The Authors. The Prostate published by Wiley Periodicals, Inc.

Chemical species of sulfur in prostate cancer cells studied by XANES spectroscopy

NASA Astrophysics Data System (ADS)

Czapla, Joanna; Kwiatek, Wojciech M.; Lekki, Janusz; Dulińska-Litewka, Joanna; Steininger, Ralph; Göttlicher, Jörg

2013-12-01

The role of sulfur in prostate cancer progression may be significant for understanding the process of carcinogenesis. This work, based on X-ray Absorption Near Edge Structure (XANES) spectroscopy, is focused on determination of sulfur chemical species occurring in prostate cancer cell lines. The experimental material consisted of four commercially available cell lines: three from metastasized prostate cancer (PC3, LNCaP, and DU145) and one, used as a control, from the non-tumourigenic peripheral zone of the prostate (PZ-HPV-7). The experiment was performed at the SUL-X beamline of the synchrotron radiation source ANKA, Karlsruhe (Germany). The K-edge XANES spectra of sulfur were analyzed by deconvolution in order to establish sulfur species that occur in prostate cancer cells and to find out whether there are any differences in their content between various cell lines. Experimental spectra were fitted in two ways: with two Gaussian peaks and one arctangent step function, and additionally by a Linear Combination Fit with spectra of reference compounds in order to obtain quantitative chemical information. All fitting procedures were performed with the Athena code (Ravel and Newville, 2005) and the results of deconvolution were used to determine the fraction of each sulfur form. The results of data analysis showed that cell lines from different metastasis had different ratio of reduced to oxidized sulfur species. The LCF analysis demonstrated that the highest content of GSH, one of the most important sulfur-bearing compounds in cells, was observed in DU145 cells. These findings may confirm the hypothesis of changes in redox balance in case of cancer initiation and progression.

Prostate cancer support groups, health literacy and consumerism: are community-based volunteers re-defining older men's health?

PubMed

Oliffe, John L; Bottorff, Joan L; McKenzie, Michael M; Hislop, T Gregory; Gerbrandt, Julieta S; Oglov, Valerie

2011-11-01

In this article we describe the connections between prostate cancer support groups (PCSGs) and men's health literacy and consumer orientation to health care services. The study findings are drawn from participant observations conducted at 16 PCSGs in British Columbia, Canada and 54 individual interviews that focused on men's experiences of attending group meetings. Men's communication and interactions at PCSGs provide important insights for how men talk about and conceptualize health and illness. For example, biomedical language often predominated at group meetings, and men used numbers and measures to engage with risk discourses in linking prostate cancer markers to various treatment options and morbidity and mortality rates. Many groups afforded opportunities for men to interact with health care providers as a means to better understand the language and logic of prostate cancer management. The health literacy skills fostered at PCSGs along with specific group-informed strategies could be mobilized in the men's subsequent clinical consultations. Consumer discourses and strategies to contest power relations with health care professionals underpinned many men's search for prostate cancer information and their commitment to assisting other men. Key were patients' rights, and perhaps responsibility, to compare diverse health products and services in making decisions across the entire trajectory of their prostate cancer. Overall, the study findings reveal PCSGs as having the capacity to contest as well as align with medical expertise and services facilitating men's transition from patient to informed health care consumers. The processes through which this occurs may direct the design of older men's health promotion programs.

PTTG1, A novel androgen responsive gene is required for androgen-induced prostate cancer cell growth and invasion

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

Zhang, Zheng; Jin, Bo; Jin, Yaqiong

Androgens (AR) play an important role in initiation and progression of prostate cancer. It has been shown that AR exert their effects mainly through the androgen-activated AR which binds to androgen response elements (AREs) in the regulatory regions of target genes to regulate the transcription of androgen-responsive genes, thus, identification of AR downstream target gene is critical to understand androgen function in prostate cancer. In this study, our results showed that androgen treatment of LNCaP cells induced PTTG1 expression, which was blocked by the androgen receptor antagonist, Casodex. Bioinformatics analysis and experiments using PTTG1 promoter deletion mutants showed that themore » PTTG1 promoter contains a putative androgen response element (ARE), which localizes in the −851 to −836 region of the promoter. Androgen activated androgen receptor (AR) binding to this ARE was confirmed by Chromatin immunoprecipitation (ChIP) assay. Furthermore, Knockdown of PTTG1 expression using short hairpin RNA significantly reduced androgen-induced LNCaP cell growth and invasion. In addition, we showed PTTG1 is highly expressed in metastasis prostate cancer tissue. These results suggest that PTTG1 is a novel downstream target gene of androgen receptor and take part in prostate cancer proliferation and metastasis. - Highlights: • Androgen treatment of LNCaP cells induced PTTG1 expression. • Knockdown of PTTG1 expression significantly reduced androgen-induced LNCaP cell growth and invasion. • PTTG1 is highly expressed in metastasis prostate cancer tissue. • PTTG1 is a novel downstream target gene of androgen receptor.« less

Super-Penetrant Androgen Receptor: Overcoming Enzalutamide Sensitivity in Castration-Resistant Prostate Cancer

DTIC Science & Technology

2016-07-01

Prostate Cancer Research Symposium- Prostate Cancer Epigenetic Reprogramming of the Androgen Receptor in Castration Resistant Prostate Cancer , May19... cancer cells rely critically on the androgen receptor (AR) for initiation, growth and progression to castration resistant prostate cancer (CRPC...Androgen receptor, castration resistant prostate cancer , Enzalutamide , kinases. 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER

The Prostate

MedlinePlus

... Publications Reports What You Need To Know About™ Prostate Cancer This booklet is about prostate cancer. Learning about medical care for your cancer ... ePub This booklet covers: The anatomy of the prostate and basics about prostate cancer Treatments for prostate ...

[The touched masculinity: a discussion about the digital rectal exam for prostate cancer prevention].

PubMed

Gomes, Romeu; do Nascimento, Elaine Ferreira; Rebello, Lúcia Emília Figueiredo de Sousa; de Araújo, Fábio Carvalho

2008-01-01

The present study aims at analyzing the meanings attributed to the digital rectal exam, seeking to problematize questions underlying the masculine discourse on the basis of aspects of the hegemonic masculinity model. Semi-structured interviews were held with 28 men in the city of Rio de Janeiro, in 2004. Among the main results is the idea that the digital rectal exam is something that violates an interdicted space, something that compromises the current understanding of masculinity, shall say, the digital rectal exam does not only affect the prostate, it also affects the masculinity, puts it to shame. We conclude that for understanding and problematizing the questions related to the prostate cancer prevention in special, and to the question of taking care of oneself from the masculine perspective in general, we need to consider the structural and symbolic aspects that underlie these questions.

Understanding variation in primary prostate cancer treatment within the Veterans Health Administration.

PubMed

Nambudiri, Vinod E; Landrum, Mary Beth; Lamont, Elizabeth B; McNeil, Barbara J; Bozeman, Samuel R; Freedland, Stephen J; Keating, Nancy L

2012-03-01

To examine the variation in prostate cancer treatment in the Veterans Health Administration (VHA)--a national, integrated delivery system. We also compared the care for older men in the VHA with that in fee-for-service Medicare. We used data from the Veterans Affairs Central Cancer Registry linked with administrative data and Surveillance, Epidemiology, and End Results-Medicare data to identify men with local or regional prostate cancer diagnosed during 2001 to 2004. We used multinomial logistic and hierarchical regression models to examine the patient, tumor, and facility characteristics associated with treatment in the VHA and, among older patients, used propensity score methods to compare primary therapy between the VHA and fee-for-service Medicare. The rates of radical prostatectomy and radiotherapy varied substantially across VHA facilities. Among the VHA patients, older age, black race/ethnicity, and greater comorbidity were associated with receiving neither radical prostatectomy nor radiotherapy. Facilities with more black patients with prostate cancer had lower rates of radical prostatectomy, and those with less availability of external beam radiotherapy had lower radiotherapy rates. The adjusted rates of radiotherapy (39.7% vs 52.0%) and radical prostatectomy (12.1% vs 15.8%) were lower and the rates of receiving neither treatment greater (48.2% vs 32.2%) in the VHA versus fee-for-service Medicare (P < .001). In the VHA, the treatment rates varied substantially across facilities, and black men received less aggressive prostate cancer treatment than white men, suggesting factors other than patient preferences influence the treatment decisions. Also, primary prostate cancer therapy for older men is less aggressive in the VHA than in fee-for-service Medicare. Copyright © 2012 Elsevier Inc. All rights reserved.

Analysis of the genomic response of human prostate cancer cells to histone deacetylase inhibitors.

PubMed

Kortenhorst, Madeleine S Q; Wissing, Michel D; Rodríguez, Ronald; Kachhap, Sushant K; Jans, Judith J M; Van der Groep, Petra; Verheul, Henk M W; Gupta, Anuj; Aiyetan, Paul O; van der Wall, Elsken; Carducci, Michael A; Van Diest, Paul J; Marchionni, Luigi

2013-09-01

Histone deacetylases (HDACs) have emerged as important targets for cancer treatment. HDAC-inhibitors (HDACis) are well tolerated in patients and have been approved for the treatment of patients with cutaneous T-cell lymphoma (CTCL). To improve the clinical benefit of HDACis in solid tumors, combination strategies with HDACis could be employed. In this study, we applied Analysis of Functional Annotation (AFA) to provide a comprehensive list of genes and pathways affected upon HDACi-treatment in prostate cancer cells. This approach provides an unbiased and objective approach to high throughput data mining. By performing AFA on gene expression data from prostate cancer cell lines DU-145 (an HDACi-sensitive cell line) and PC3 (a relatively HDACi-resistant cell line) treated with HDACis valproic acid or vorinostat, we identified biological processes that are affected by HDACis and are therefore potential treatment targets for combination therapy. Our analysis revealed that HDAC-inhibition resulted among others in upregulation of major histocompatibility complex (MHC) genes and deregulation of the mitotic spindle checkpoint by downregulation of genes involved in mitosis. These findings were confirmed by AFA on publicly available data sets from HDACi-treated prostate cancer cells. In total, we analyzed 375 microarrays with HDACi treated and non-treated (control) prostate cancer cells. All results from this extensive analysis are provided as an online research source (available at the journal's website and at http://luigimarchionni.org/HDACIs.html). By publishing this data, we aim to enhance our understanding of the cellular changes after HDAC-inhibition, and to identify novel potential combination strategies with HDACis for the treatment of prostate cancer patients.

Analysis of the genomic response of human prostate cancer cells to histone deacetylase inhibitors

PubMed Central

Kortenhorst, Madeleine SQ; Wissing, Michel D; Rodriguez, Ronald; Kachhap, Sushant K; Jans, Judith JM; Van der Groep, Petra; Verheul, Henk MW; Gupta, Anuj; Aiyetan, Paul O; van der Wall, Elsken; Carducci, Michael A; Van Diest, Paul J; Marchionni, Luigi

2013-01-01

Histone deacetylases (HDACs) have emerged as important targets for cancer treatment. HDAC-inhibitors (HDACis) are well tolerated in patients and have been approved for the treatment of patients with cutaneous T-cell lymphoma (CTCL). To improve the clinical benefit of HDACis in solid tumors, combination strategies with HDACis could be employed. In this study, we applied Analysis of Functional Annotation (AFA) to provide a comprehensive list of genes and pathways affected upon HDACi-treatment in prostate cancer cells. This approach provides an unbiased and objective approach to high throughput data mining. By performing AFA on gene expression data from prostate cancer cell lines DU-145 (an HDACi-sensitive cell line) and PC3 (a relatively HDACi-resistant cell line) treated with HDACis valproic acid or vorinostat, we identified biological processes that are affected by HDACis and are therefore potential treatment targets for combination therapy. Our analysis revealed that HDAC-inhibition resulted among others in upregulation of major histocompatibility complex (MHC) genes and deregulation of the mitotic spindle checkpoint by downregulation of genes involved in mitosis. These findings were confirmed by AFA on publicly available data sets from HDACi-treated prostate cancer cells. In total, we analyzed 375 microarrays with HDACi treated and non-treated (control) prostate cancer cells. All results from this extensive analysis are provided as an online research source (available at the journal’s website and at http://luigimarchionni.org/HDACIs.html). By publishing this data, we aim to enhance our understanding of the cellular changes after HDAC-inhibition, and to identify novel potential combination strategies with HDACis for the treatment of prostate cancer patients. PMID:23880963

Racial differences in the relationship between clinical prostatitis, presence of inflammation in benign prostate and subsequent risk of prostate cancer.

PubMed

Rybicki, B A; Kryvenko, O N; Wang, Y; Jankowski, M; Trudeau, S; Chitale, D A; Gupta, N S; Rundle, A; Tang, D

2016-06-01

Epidemiologic studies, primarily done in white men, suggest that a history of clinically-diagnosed prostatitis increases prostate cancer risk, but that histological prostate inflammation decreases risk. The relationship between a clinical history of prostatitis and histologic inflammation in terms of how these two manifestations of prostatic inflammation jointly contribute to prostate cancer risk and whether racial differences exist in this relationship is uncertain. Using a nested design within a cohort of men with benign prostate tissue specimens, we analyzed the data on both clinically-diagnosed prostatitis (NIH categories I-III) and histological inflammation in 574 prostate cancer case-control pairs (345 white, 229 African American). Clinical prostatitis was not associated with increased prostate cancer risk in the full sample, but showed a suggestive inverse association with prostate cancer in African Americans (odds ratio (OR)=0.47; 95% confidence interval (CI)=0.27-0.81). In whites, clinical prostatitis increased risk by 40%, but was only associated with a significant increased prostate cancer risk in the absence of evidence of histological inflammation (OR=3.56; 95% CI=1.15-10.99). Moreover, PSA velocity (P=0.008) and frequency of PSA testing (P=0.003) were significant modifiers of risk. Clinical prostatitis increased risk of prostate cancer almost three-fold (OR=2.97; 95% CI=1.40-6.30) in white men with low PSA velocity and about twofold in white men with more frequent PSA testing (OR=1.91; 95% CI=1.09-3.35). In our cohort of men with benign prostate specimens, race, and histological inflammation were important cofactors in the relationship between clinical prostatitis and prostate cancer. Clinical prostatitis was associated with a slightly decreased risk for prostate cancer in African American men. In white men, the relationship between clinical prostatitis and prostate cancer risk was modified by histological prostatic inflammation, PSA velocity, and frequency of PSA testing-suggesting a complex interplay between these indications of prostatic inflammation and prostate cancer detection.

Racial differences in the relationship between clinical prostatitis, presence of inflammation in benign prostate and subsequent risk of prostate cancer

PubMed Central

Rybicki, BA; Kryvenko, ON; Wang, Y; Jankowski, M; Trudeau, S; Chitale, DA; Gupta, NS; Rundle, A; Tang, D

2016-01-01

BACKGROUND Epidemiologic studies, primarily done in white men, suggest that a history of clinically-diagnosed prostatitis increases prostate cancer risk, but that histological prostate inflammation decreases risk. The relationship between a clinical history of prostatitis and histologic inflammation in terms of how these two manifestations of prostatic inflammation jointly contribute to prostate cancer risk and whether racial differences exist in this relationship is uncertain. METHODS Using a nested design within a cohort of men with benign prostate tissue specimens, we analyzed the data on both clinically-diagnosed prostatitis (NIH categories I–III) and histological inflammation in 574 prostate cancer case-control pairs (345 white, 229 African American). RESULTS Clinical prostatitis was not associated with increased prostate cancer risk in the full sample, but showed a suggestive inverse association with prostate cancer in African Americans (odds ratio (OR) = 0.47; 95% confidence interval (CI) = 0.27–0.81). In whites, clinical prostatitis increased risk by 40%, but was only associated with a significant increased prostate cancer risk in the absence of evidence of histological inflammation (OR = 3.56; 95% CI = 1.15–10.99). Moreover, PSA velocity (P = 0.008) and frequency of PSA testing (P = 0.003) were significant modifiers of risk. Clinical prostatitis increased risk of prostate cancer almost three-fold (OR = 2.97; 95% CI = 1.40–6.30) in white men with low PSA velocity and about twofold in white men with more frequent PSA testing (OR = 1.91; 95% CI = 1.09–3.35). CONCLUSIONS In our cohort of men with benign prostate specimens, race, and histological inflammation were important cofactors in the relationship between clinical prostatitis and prostate cancer. Clinical prostatitis was associated with a slightly decreased risk for prostate cancer in African American men. In white men, the relationship between clinical prostatitis and prostate cancer risk was modified by histological prostatic inflammation, PSA velocity, and frequency of PSA testing—suggesting a complex interplay between these indications of prostatic inflammation and prostate cancer detection. PMID:26620738

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

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.

[Prostate cancer and new hormonal treatments: mechanism of action and main clinical results].

PubMed

Neuzillet, Y; Flamand, V; Lebdai, S; Villers, A; Lebret, T

2013-10-01

New drugs have recently been developed, through a better understanding of the mechanisms involved in the progression of prostate cancer, including castration-resistant ones (CRPC). This article aims to describe the mechanisms of action of these new hormonal treatments and their major clinical outcomes and development programs. A bibliographic research in French and English using Medline(®) and Embase(®) using the keywords "castration-resistant prostate cancer", "abiraterone acetate", "orteronel", "enzalutamide", and "clinical trials" was performed. the androgen signaling pathway remains the cornerstone of advanced cancers management. Hence, some molecules target the androgen biosynthesis, as abiraterone acetate and orteronel, which are selective inhibitors of the enzyme CYP17. Others act as antagonists of the androgen receptor: the enzalutamide, RNA-509 and ODM201. Finally, galeterone combines the two effects. Progress conferred by these molecules in terms of overall survival and quality of life in patients with metastatic CRPC, suggest that their use at earlier stages of the disease could reduce morbidity and mortality from prostate cancer. Determining the best strategy for sequence or combination therapy to optimize the use of these new molecules should be investigated. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Prostate-derived Ets factor, an oncogenic driver in breast cancer.

PubMed

Sood, Ashwani K; Geradts, Joseph; Young, Jessica

2017-05-01

Prostate-derived Ets factor (PDEF), a member of the Ets family of transcription factors, differs from other family members in its restricted expression in normal tissues and its unique DNA-binding motif. These interesting attributes coupled with its aberrant expression in cancer have rendered PDEF a focus of increasing interest by tumor biologists. This review provides a current understanding of the characteristics of PDEF expression and its role in breast cancer. The bulk of the evidence is consistent with PDEF overexpression in most breast tumors and an oncogenic role for this transcription factor in breast cancer. In addition, high PDEF expression in estrogen receptor-positive breast tumors showed significant correlation with poor overall survival in several independent cohorts of breast cancer patients. Together, these findings demonstrate PDEF to be an oncogenic driver of breast cancer and a biomarker of poor prognosis in this cancer. Based on this understanding and the limited expression of PDEF in normal human tissues, the development of PDEF-based therapeutics for prevention and treatment of breast cancer is also discussed.

Biomarkers for prostate cancer detection and progression: Beyond prostate-specific antigen.

PubMed

Berney, Daniel M

2010-04-01

Prostate cancer is a major health problem with an incompletely understood pathogenesis and etiology. The advent of the prostate-specific antigen (PSA) test in the 1980s caused a revolution in how the disease was detected, but the evidence for PSA as a screening test is deficient. Biomarkers have been investigated, both for detection and discrimination of indolent from aggressive cancers. Refinements to the PSA test have been proposed but for practical and evidence-based reasons none have translated through to widespread clinical use. Of the novel biomarkers, the most promising is the prostate cancer antigen 3 (PCA3) test. New biomarkers to predict aggressive disease are even more contentious. The pathological grade of tumor remains the most powerful biomarker of prognosis. Other proven variables include tumor extent on biopsy and serum PSA. Tissue biomarkers have proven unhelpful due to a variable and biased literature with multiple methodological flaws, but Ki-67 probably shows more promise than any other current tissue biomarker. The recent discovery of a family of fusion genes in the prostate has led to considerable discussion on their prognostic role. Dissection of the genetic basis of the disease may lead to discoveries that will enhance our understanding and aid the search for prognostically valuable biomarkers. Copyright 2010 Prous Science, S.A.U. or its licensors. All rights reserved.

Molecular pathology and prostate cancer therapeutics: from biology to bedside.

PubMed

Rodrigues, Daniel Nava; Butler, Lisa M; Estelles, David Lorente; de Bono, Johann S

2014-01-01

Prostate cancer (PCa) is the second most commonly diagnosed malignancy in men and has an extremely heterogeneous clinical behaviour. The vast majority of PCas are hormonally driven diseases in which androgen signalling plays a central role. The realization that castration-resistant prostate cancer (CRPC) continues to rely on androgen signalling prompted the development of new, effective androgen blocking agents. As the understanding of the molecular biology of PCas evolves, it is hoped that stratification of prostate tumours into distinct molecular entities, each with its own set of vulnerabilities, will be a feasible goal. Around half of PCas harbour rearrangements involving a member of the ETS transcription factor family. Tumours without this rearrangement include SPOP mutant as well as SPINK1-over-expressing subtypes. As the number of targeted therapy agents increases, it is crucial to determine which patients will benefit from these interventions and molecular pathology will be key in this respect. In addition to directly targeting cells, therapies that modify the tumour microenvironment have also been successful in prolonging the lives of PCa patients. Understanding the molecular aspects of PCa therapeutics will allow pathologists to provide core recommendations for patient management. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Effects of anti-cancer drug doxorubicin on endogenous biomarkers NAD(P)H, FAD and Trp in prostate cancer cells: a FLIM Study

NASA Astrophysics Data System (ADS)

Rehman Alam, Shagufta; Wallrabe, Horst; Svindrych, Zdenek; Christopher, Kathryn G.; Chandra, Dhyan; Periasamy, Ammasi

2017-02-01

Fluorescence Lifetime Imaging Microscopy (FLIM) can be used to identify changes in metabolic activity during cancer progression and upon anti-cancer drug treatment. Prostate cancer (PCa) is one of the leading cancers in men in the USA. This research focusses on understanding the lifetime changes of endogenous biomarkers: NAD(P)H, FAD and Trp in LNCaP cells upon treatment with doxorubicin using our 3-channel FLIM approach. The LNCaP cells were treated with doxorubicin for 24hr. Images using FLIM of LNCaP control and treated cells were acquired on Zeiss 780 multiphoton confocal microscope coupled with B and H TCSPC FLIM board. After FLIM data fitting and processing we observed increase in the mean fluorescence lifetime of Trp, NAD(P)H and FAD with doxorubicin treatment. Additionally, we saw reduction in the NAD(P)H/FAD redox ratio with doxorubicin treatment. Our results identify the changes in the lifetime of these endogenous biomarkers and in the cellular redox state as a metabolic response with doxorubicin treatment in prostate cancer cells.

β-Carotene 9',10' Oxygenase Modulates the Anticancer Activity of Dietary Tomato or Lycopene on Prostate Carcinogenesis in the TRAMP Model.

PubMed

Tan, Hsueh-Li; Thomas-Ahner, Jennifer M; Moran, Nancy E; Cooperstone, Jessica L; Erdman, John W; Young, Gregory S; Clinton, Steven K

2017-02-01

The hypothesis that dietary tomato consumption or the intake of the carotenoid lycopene inhibits prostate cancer arose from epidemiologic studies and is supported by preclinical rodent experiments and in vitro mechanistic studies. We hypothesize that variation in activity of carotenoid cleavage enzymes, such as β-carotene 9',10'-oxygenase (BCO2), may alter the impact of dietary tomato and lycopene on prostate carcinogenesis and therefore examined this relationship in the TRAMP model. Starting at 3 weeks of age, TRAMP:Bco2 +/+ and TRAMP:Bco2 -/- mice were fed either AIN-93G control, or semipurified diets containing 10% tomato powder or 0.25% lycopene beadlets until 18 weeks of age. Both tomato- and lycopene-fed TRAMP:Bco2 -/- mice had significantly greater serum concentrations of total, 5-cis, other cis, and all-trans lycopene than TRAMP:Bco2 +/+ mice. Tomato- and lycopene-fed mice had a lower incidence of prostate cancer compared with the control-fed mice. Although Bco2 genotype alone did not significantly change prostate cancer outcome in the control AIN-93G-fed mice, the abilities of lycopene and tomato feeding to inhibit prostate carcinogenesis were significantly attenuated by the loss of Bco2 (P interaction = 0.0004 and 0.0383, respectively). Overall, dietary tomato and lycopene inhibited the progression of prostate cancer in TRAMP in a Bco2 genotype-specific manner, potentially implicating the anticancer activity of lycopene cleavage products. This study suggests that genetic variables impacting carotenoid metabolism and accumulation can impact anticancer activity and that future efforts devoted to understanding the interface between tomato carotenoid intake, host genetics, and metabolism will be necessary to clearly elucidate their interactive roles in human prostate carcinogenesis. Cancer Prev Res; 10(2); 161-9. ©2016 AACR. ©2016 American Association for Cancer Research.

Synergistic interaction of benign prostatic hyperplasia and prostatitis on prostate cancer risk

PubMed Central

Hung, S-C; Lai, S-W; Tsai, P-Y; Chen, P-C; Wu, H-C; Lin, W-H; Sung, F-C

2013-01-01

Background: The incidence of prostate cancer is much lower in Asian men than in Western men. This study investigated whether prostate cancer is associated with prostatitis, benign prostatic hyperplasia (BPH), and other medical conditions in the low-incidence population. Methods: From the claims data obtained from the universal National Health Insurance of Taiwan, we identified 1184 patients with prostate cancer diagnosed from 1997 to 2008. Controls comprised 4736 men randomly selected from a cancer-free population. Both groups were 50 years of age or above. Medical histories between the two groups were compared. Results: Multivariate logistic regression analysis showed that prostatitis and BPH had stronger association with prostate cancer than the other medical conditions tested. Compared with men without prostatitis and BPH, a higher odds ratio (OR) for prostate cancer was associated with BPH (26.2, 95% confidence interval (CI) 20.8–33.0) than with prostatitis (10.5, 95% CI=3.36–32.7). Men with both conditions had an OR of 49.2 (95% CI=34.7–69.9). Conclusion: Men with prostate cancer have strong association with prostatitis and/or BPH. Prostatitis interacts with BPH, resulting in higher estimated relative risk of prostate cancer in men suffering from both conditions. PMID:23612451

Ciprofloxacin as a prophylactic agent against prostate cancer: a "two hit" hypothesis.

PubMed

Kloskowski, T; Gurtowska, N; Bajek, A; Drewa, T

2012-02-01

More evidence indicate that prostate inflammation can lead to prostate cancer development. Prostate cancer affects elderly men. Prostate cancer prophylaxis is an important issue because life expectancy is very long now. Ciprofloxacin is an antibacterial agent used mainly in urinary tract infections and prostate inflammation. This drug acts also against cancer cells by the inhibition of topoisomerase II. These properties should allow it to inhibit the development of prostate cancer. Firstly, ciprofloxacin can stop the acute and chronic prostate inflammation which can lead to cancer development. Secondly, ciprofloxacin can potentially kill prostate cancer cells in their early stage of development. Ciprofloxacin accumulates mainly in the prostate after oral intake thus ciprofloxacin seems to be a perfect candidate as a prophylactic agent. Copyright © 2011 Elsevier Ltd. All rights reserved.

Prostate cancer, prostate cancer death, and death from other causes, among men with metabolic aberrations.

PubMed

Häggström, Christel; Stocks, Tanja; Nagel, Gabriele; Manjer, Jonas; Bjørge, Tone; Hallmans, Göran; Engeland, Anders; Ulmer, Hanno; Lindkvist, Björn; Selmer, Randi; Concin, Hans; Tretli, Steinar; Jonsson, Håkan; Stattin, Pär

2014-11-01

Few previous studies of metabolic aberrations and prostate cancer risk have taken into account the fact that men with metabolic aberrations have an increased risk of death from causes other than prostate cancer. The aim of this study was to calculate, in a real-life scenario, the risk of prostate cancer diagnosis, prostate cancer death, and death from other causes. In the Metabolic Syndrome and Cancer Project, prospective data on body mass index, blood pressure, glucose, cholesterol, and triglycerides were collected from 285,040 men. Risks of prostate cancer diagnosis, prostate cancer death, and death from other causes were calculated by use of competing risk analysis for men with normal (bottom 84%) and high (top 16%) levels of each factor, and a composite score. During a mean follow-up period of 12 years, 5,893 men were diagnosed with prostate cancer, 1,013 died of prostate cancer, and 26,328 died of other causes. After 1996, when prostate-specific antigen testing was introduced, men up to age 80 years with normal metabolic levels had 13% risk of prostate cancer, 2% risk of prostate cancer death, and 30% risk of death from other causes, whereas men with metabolic aberrations had corresponding risks of 11%, 2%, and 44%. In contrast to recent studies using conventional survival analysis, in a real-world scenario taking risk of competing events into account, men with metabolic aberrations had lower risk of prostate cancer diagnosis, similar risk of prostate cancer death, and substantially higher risk of death from other causes compared with men who had normal metabolic levels.

Penile rehabilitation following prostate cancer treatment: review of current literature

PubMed Central

Clavell-Hernandez, Jonathan; Wang, Run

2015-01-01

Radical prostatectomy (RP) and radiotherapy (RT) are highly effective in improving prostate cancer survival. However, both have a detrimental effect on erectile function (EF). Penile rehabilitation consists of understanding the mechanisms that cause erectile dysfunction (ED) and utilizing pharmacologic agents, devices or interventions to promote male sexual function. For the past decade, many researchers have pursued to define effective treatment modalities to improve ED after prostate cancer treatment. Despite the understanding of the mechanisms and well-established rationale for postprostate treatment penile rehabilitation, there is still no consensus regarding effective rehabilitation programs. This article reviews a contemporary series of trials that assess penile rehabilitation and explore treatment modalities that might play a role in the future. Published data and trials related to penile rehabilitation after RP and RT were reviewed and presented. Although recent trials have shown that most therapies are well-tolerated and aid in some degree on EF recovery, we currently do not have tangible evidence to recommend an irrefutable penile rehabilitation algorithm. However, advancements in research and technology will ultimately create and refine management options for penile rehabilitation. PMID:25851656

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.

Sleep disruption, chronotype, shift work, and prostate cancer risk and mortality: a 30-year prospective cohort study of Finnish twins.

PubMed

Dickerman, Barbra A; Markt, Sarah C; Koskenvuo, Markku; Hublin, Christer; Pukkala, Eero; Mucci, Lorelei A; Kaprio, Jaakko

2016-11-01

Sleep disruption and shift work have been associated with cancer risk, but epidemiologic evidence for prostate cancer remains limited. We aimed to prospectively investigate the association between midlife sleep- and circadian-related parameters and later prostate cancer risk and mortality in a population-based cohort of Finnish twins. Data were drawn from the Older Finnish Twin Cohort and included 11,370 twins followed from 1981 to 2012. Over the study period, 602 incident cases of prostate cancer and 110 deaths from prostate cancer occurred. Cox regression was used to evaluate associations between midlife sleep duration, sleep quality, chronotype, and shift work with prostate cancer risk and prostate cancer-specific mortality. Within-pair co-twin analyses were employed to account for potential familial confounding. Compared to "definite morning" types, "somewhat evening" types had a significantly increased risk of prostate cancer (HR 1.3; 95 % CI 1.1, 1.6). Chronotype significantly modified the relationship between shift work and prostate cancer risk (p-interaction <0.001). We found no significant association between sleep duration, sleep quality, or shift work and prostate cancer risk in the overall analyses and no significant association between any sleep- or circadian-related parameter and risk in co-twin analyses. Neither sleep- nor circadian-related parameters were significantly associated with prostate cancer-specific mortality. The association between sleep disruption, chronotype, and shift work with prostate cancer risk and mortality has never before been studied in a prospective study of male twins. Our findings suggest that chronotype may be associated with prostate cancer risk and modify the association between shift work and prostate cancer risk. Future studies of circadian disruption and prostate cancer should account for this individual-level characteristic.

Contribution of Caudal Müllerian Duct Mesenchyme to Prostate Development

PubMed Central

Brechka, Hannah; McAuley, Erin M.; Lamperis, Sophia M.; Paner, Gladell P.

2016-01-01

A fundamental understanding of prostate development and tissue homeostasis has the high potential to reveal mechanisms for prostate disease initiation and identify novel therapeutic approaches for disease prevention and treatment. Our current understanding of prostate lineage specification stems from the use of developmental model systems that rely upon the embryonic preprostatic urogenital sinus mesenchyme to induce the formation of mature prostate epithelial cells. It is unclear, however, how the urogenital sinus epithelium can derive both adult urethral glands and prostate epithelia. Furthermore, the vast disparity in disease initiation between these two glands highlights key developmental factors that predispose prostate epithelia to hyperplasia and cancer. In this study we demonstrate that the caudal Müllerian duct mesenchyme (CMDM) drives prostate epithelial differentiation and is a key determinant in cell lineage specification between urethral glands and prostate epithelia. Utilizing both human embryonic stem cells and mouse embryonic tissues, we document that the CMDM is capable of inducing the specification of androgen receptor, prostate-specific antigen, NKX3.1, and Hoxb13-positive prostate epithelial cells. These results help to explain key developmental differences between prostate and urethral gland differentiation, and implicate factors secreted by the caudal Müllerian duct as novel targets for prostate disease prevention and treatment. PMID:27595922

Evolution of a CDC Public Health Research Agenda for Low-Risk Prostate Cancer

PubMed Central

Hall, Ingrid J.; Smith, Judith Lee

2016-01-01

Men with prostate cancer face difficult choices when selecting a therapy for localized prostate cancer. Comparative data from controlled studies are lacking and clinical opinions diverge about the benefits and harms of treatment options. Consequently, there is limited guidance for patients regarding the impact of treatment decisions on quality of life. There are opportunities for public health to intervene at several decision-making points. Information on typical quality of life outcomes associated with specific prostate cancer treatments could help patients select treatment options. From 2003 to present, the Division of Cancer Prevention and Control at CDC has supported projects to explore patient information-seeking behavior post-diagnosis, caregiver and provider involvement in treatment decision making, and patient quality of life following prostate cancer treatment. CDC's work also includes research that explores barriers and facilitators to the presentation of active surveillance as a viable treatment option and promotes equal access to information for men and their caregivers. This article provides an overview of the literature and considerations that initiated establishing a prospective public health research agenda around treatment decision making. Insights gathered from CDC-supported studies are poised to enhance understanding of the process of shared decision making and the influence of patient, caregiver, and provider preferences on the selection of treatment choices. These findings provide guidance about attributes that maximize patient experiences in survivorship, including optimal quality of life and patient and caregiver satisfaction with information, treatment decisions, and subsequent care. PMID:26590643

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.

Preclinical Evaluation of the Supercritical Extract of Azadirachta Indica (Neem) Leaves In Vitro and In Vivo on Inhibition of Prostate Cancer Tumor Growth

PubMed Central

Wu, Qiang; Kohli, Manish; Bergen, H. Robert; Cheville, John C.; Karnes, R. Jeffrey; Cao, Hong; Young, Charles Y.F.; Tindall, Donald J.; McNiven, Mark A.; Donkena, Krishna Vanaja

2015-01-01

Azadirachta indica, commonly known as neem, has gained worldwide prominence because of its medical properties, namely antitumor, antiviral, anti-inflammatory, antihyperglycemic, antifungal, and antibacterial activities. Despite these promising results, gaps remain in our understanding of the molecular mechanism of action of neem compounds and their potential for use in clinical trials. We investigated supercritical extract of neem leaves (SENL) for the following: molecular targets in vitro, in vivo efficacy to inhibit tumor growth, and bioactive compounds that exert antitumor activity. Treatment of LNCaP-luc2 prostate cancer cells with SENL suppressed dihydrotestosterone-induced androgen receptor and prostate-specific antigen levels. SENL inhibited integrin β1, calreticulin, and focal adhesion kinase activation in LNCaP-luc2 and PC3 prostate cancer cells. Oral administration of SENL significantly reduced LNCaP-luc2 xenograft tumor growth in mice with the formation of hyalinized fibrous tumor tissue, reduction in the prostate-specific antigen, and increase in AKR1C2 levels. To identify the active anticancer compounds, we fractionated SENL by high-pressure liquid chromatography and evaluated 16 peaks for cytotoxic activity. Four of the 16 peaks exhibited significant cytotoxic activity against prostate cancer cells. Mass spectrometry of the isolated peaks suggested the compounds with cytotoxic activity were nimbandiol, nimbolide, 2′,3′-dihydronimbolide, and 28-deoxonim-bolide. Analysis of tumor tissue and plasma samples from mice treated with SENL indicated 28-deoxonim-bolide and nimbolide as the bioactive compounds. Overall, our data revealed the bioactive compounds in SENL and suggested that the anticancer activity could be mediated through alteration in androgen receptor and calreticulin levels in prostate cancer. PMID:24674886

LuCaP Prostate Cancer Patient-Derived Xenografts Reflect the Molecular Heterogeneity of Advanced Disease an--d Serve as Models for Evaluating Cancer Therapeutics.

PubMed

Nguyen, Holly M; Vessella, Robert L; Morrissey, Colm; Brown, Lisha G; Coleman, Ilsa M; Higano, Celestia S; Mostaghel, Elahe A; Zhang, Xiaotun; True, Lawrence D; Lam, Hung-Ming; Roudier, Martine; Lange, Paul H; Nelson, Peter S; Corey, Eva

2017-05-01

Metastatic prostate cancer is a common and lethal disease for which there are no therapies that produce cures or long-term durable remissions. Clinically relevant preclinical models are needed to increase our understanding of biology of this malignancy and to evaluate new agents that might provide effective treatment. Our objective was to establish and characterize patient-derived xenografts (PDXs) from advanced prostate cancer (PC) for investigation of biology and evaluation of new treatment modalities. Samples of advanced PC obtained from primary prostate cancer obtained at surgery or from metastases collected at time of death were implanted into immunocompromised mice to establish PDXs. Established PDXs were propagated in vivo. Genomic, transcriptomic, and STR profiles were generated. Responses to androgen deprivation and docetaxel in vivo were characterized. We established multiple PDXs (LuCaP series), which represent the major genomic and phenotypic features of the disease in humans, including amplification of androgen receptor, PTEN deletion, TP53 deletion and mutation, RB1 loss, TMPRSS2-ERG rearrangements, SPOP mutation, hypermutation due to MSH2/MSH6 genomic aberrations, and BRCA2 loss. The PDX models also exhibit variation in intra-tumoral androgen levels. Our in vivo results show heterogeneity of response to androgen deprivation and docetaxel, standard therapies for advanced PC, similar to the responses of patients to these treatments. The LuCaP PDX series reflects the diverse molecular composition of human castration-resistant PC and allows for hypothesis-driven cause-and-effect studies of mechanisms underlying treatment response and resistance. Prostate 77: 654-671, 2017. © 2017 The Authors. The Prostate Published by Wiley Periodicals, Inc. © 2017 The Authors. The Prostate Published by Wiley Periodicals, Inc.

Obesity and prostate cancer detection: insights from three national surveys

PubMed Central

Parekh, Niyati; Lin, Yong; DiPaola, Robert S.; Marcella, Stephen; Lu-Yao, Grace

2013-01-01

Background Previous studies suggest that obesity is associated with higher prostate cancer progression and mortality despite an association with lower prostate cancer incidence. This study aims to better understand these apparently inconsistent relationships among obese men, by combining evidence from three nationally representative cross-sectional surveys. Methods We evaluated relationships between obesity and (1) testosterone concentrations in the Third National Health and Nutrition Examination Survey (NHANES III; n=845), (2) prostate-specific antigen (PSA) in NHANES 2001–2004 (n=2,458) and (3) prostate biopsy rates in the National Health Interview Survey (NHIS 2000; n=4,789) population. Mean testosterone, PSA concentrations and biopsy rates were computed for body mass index (BMI) categories. Results Testosterone concentrations were inversely associated with obesity (p-trend<0.0001) in NHANES III. In NHANES 2001–2004 obese (BMI >35) versus lean (BMI <25) men were less likely to have PSA concentrations that reached the biopsy threshold of >4 ng/ml (3% versus 8%; p<0.0001). Among NHIS participants all BMI groups had similar rates of PSA testing (p=0.24). However, among men who had PSA tests, 11% of men with BMI >30 versus 16% with BMI <25, achieved a PSA threshold of 4 ng/ml; p=0.01. Furthermore, biopsy rates were lower among men with BMI >30 versus BMI <25 in NHIS participants (4.6% vs. 5.8%; p=0.05). Conclusions Obesity was associated with lower PSA-driven biopsy rates. These data support further studies to test the hypothesis that obesity affects prostate cancer detection independent of prostate cancer risk by decreasing the PSA-driven biopsy rates. PMID:20800152

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

Tyldesley, Scott, E-mail: styldesl@bccancer.bc.c; Delaney, Geoff; Foroudi, Farshad

Purpose: Estimates of the need for radiotherapy (RT) using different methods (criterion based benchmarking [CBB]and the Canadian [C-EBEST]and Australian [A-EBEST]epidemiologically based estimates) exist for various cancer sites. We compared these model estimates to actual RT rates for lung, breast, and prostate cancers in British Columbia (BC). Methods and Materials: All cases of lung, breast, and prostate cancers in BC from 1997 to 2004 and all patients receiving RT within 1 year (RT{sub 1Y}) and within 5 years (RT{sub 5Y}) of diagnosis were identified. The RT{sub 1Y} and RT{sub 5Y} proportions in health regions with a cancer center for the mostmore » recent year were then calculated. RT rates were compared with CBB and EBEST estimates of RT needs. Variation was assessed by time and region. Results: The RT{sub 1Y} in regions with a cancer center for lung, breast, and prostate cancers were 51%, 58%, and 33% compared with 45%, 57%, and 32% for C-EBEST and 41%, 61%, and 37% for CBB models. The RT{sub 5Y} rates in regions with a cancer center for lung, breast, and prostate cancers were 59%, 61%, and 40% compared with 61%, 66%, and 61% for C-EBEST and 75%, 83%, and 60% for A-EBEST models. The RT{sub 1Y} rates increased for breast and prostate cancers. Conclusions: C-EBEST and CBB model estimates are closer to the actual RT rates than the A-EBEST estimates. Application of these model estimates by health care decision makers should be undertaken with an understanding of the methods used and the assumptions on which they were based.« less

Relative Risks for Lethal Prostate Cancer Based on Complete Family History of Prostate Cancer Death.

PubMed

Albright, Frederick S; Stephenson, Robert A; Agarwal, Neeraj; Cannon-Albright, Lisa A

2017-01-01

There are few published familial relative risks (RR) for lethal prostate cancer. This study estimates RRs for lethal prostate cancer based on comprehensive family history data, with the goal of improving identification of those men at highest risk of dying from prostate cancer. We used a population-based genealogical resource linked to a statewide electronic SEER cancer registry and death certificates to estimate relative risks (RR) for death from prostate cancer based upon family history. Over 600,000 male probands were analyzed, representing a variety of family history constellations of lethal prostate cancer. RR estimates were based on the ratio of the observed to the expected number of lethal prostate cancer cases using internal rates. RRs for lethal prostate cancer based on the number of affected first-degree relatives (FDR) ranged from 2.49 (95% CI: 2.27, 2.73) for exactly 1 FDR to 5.30 (2.13, 10.93) for ≥3 affected FDRs. In an absence of affected FDRs, increased risk was also significant for increasing numbers of affected second-degree or third degree relatives. Equivalent risks were observed for similar maternal and paternal family history. This study provides population-based estimates of lethal prostate cancer risk based on lethal prostate cancer family history. Many family history constellations associated with two to greater than five times increased risk for lethal prostate cancer were identified. These lethal prostate cancer risk estimates hold potential for use in identification, screening, early diagnosis, and treatment of men at high risk for death from prostate cancer. Prostate77:41-48, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Inhibition of microRNA-500 has anti-cancer effect through its conditional downstream target of TFPI in human prostate cancer.

PubMed

Cai, Bing; Chen, Wei; Pan, Yue; Chen, Hongde; Zhang, Yirong; Weng, Zhiliang; Li, Yeping

2017-07-01

We investigated the prognostic potential and regulatory mechanism of microRNA-500 (miR-500), and human gene of tissue factor pathway inhibitor (TFPI) in prostate cancer. MiR-500 expression was assessed by qRT-PCR in prostate cancer cell lines and primary tumors. Cancer patients' clinicopathological factors and overall survival were analyzed according to endogenous miR-500 level. MiR-500 was downregulated in DU145 and VCaP cells. Its effect on prostate cancer proliferation, invasion in vitro, and tumorigenicity in vivo, were probed. Possible downstream target of miR-500, TFPI was assessed by luciferase assay and qRT-PCR in prostate cancer cells. In miR-500-downregulated DU145 and VCaP cells, TFPI was silenced to see whether it was directly involved in the regulation of miR-500 in prostate cancer. TFPI alone was either upregulated or downregulated in DU145 and VCaP cells. Their effect on prostate cancer development was further evaluated. MiR-500 is upregulated in both prostate cancer cells and primary tumors. In prostate cancer patients, high miR-500 expression is associated with poor prognosis and overall survival. In DU145 and VCaP cells, miR-500 downregulation inhibited cancer proliferation, invasion in vitro, and explant growth in vivo. TFPI was verified to be associated with miR-500 in prostate cancer. Downregulation of TFPI reversed anti-cancer effects of miR-500 downregulation in prostate cancer cells. However, neither TFPI upregulation nor downregulation alone had any functional impact on prostate cancer development. MiR-500 may be a potential biomarker and molecular target in prostate cancer. TFPI may conditionally regulate prostate cancer in miR-500-downregualted prostate cancer cells. © 2017 Wiley Periodicals, Inc.

Repeat Prostate Biopsy Practice Patterns in a Statewide Quality Improvement Collaborative.

PubMed

Burks, Frank N; Hu, Jonathan C; Telang, Dinesh; Liu, Alice; Hawken, Scott; Montgomery, Zack; Linsell, Susan; Montie, James E; Miller, David C; Ghani, Khurshid R

2017-08-01

We examined rebiopsies in MUSIC (Michigan Urological Surgery Improvement Collaborative) to understand adherence to guidelines recommending repeat prostate biopsy in patients with multifocal high grade prostatic intraepithelial neoplasia or atypical small acinar proliferation. We analyzed data on men undergoing repeat biopsy, practice patterns and cancer detection rates. Multivariate regression modeling was used to calculate the proportion of patients undergoing rebiopsy. We used claims data to validate the treatment classification in MUSIC. To understand reasons for not performing rebiopsy we reviewed records of a sample of patients with atypical small acinar proliferation. We identified 5,375 men with a negative biopsy, of whom 411 (7.6%) underwent repeat biopsy. In 718 men with high grade prostatic intraepithelial neoplasia, 350 with atypical small acinar proliferation and 587 with high grade prostatic intraepithelial neoplasia and atypical small acinar proliferation or atypical small acinar proliferation alone at initial biopsy the rebiopsy rate was 20.7%, 42.5% and 55.6%, respectively. The adjusted proportion of patients with rebiopsy in each practice ranged from 0% to 17.2% (p <0.001). The overall cancer detection rate at rebiopsy was 39.3%. It was highest after atypical small acinar proliferation (adjusted probability 0.39, 95% CI 0.30-0.48), and after high grade prostatic intraepithelial neoplasia and atypical small acinar proliferation (adjusted probability 0.50, 95% CI 0.35-0.65). The greatest Gleason 7 or greatest detection rate of 41.1% was found in patients with high grade prostatic intraepithelial neoplasia and atypical small acinar proliferation. Chart review revealed that 45.5% of patients with atypical small acinar proliferation underwent prostate specific antigen testing instead of rebiopsy while 36% failed to undergo rebiopsy despite a recommendation. Rebiopsy rates vary in Michigan practices with relatively low use in men with high grade prostatic intraepithelial neoplasia and atypical small acinar proliferation or atypical small acinar proliferation alone. Quality improvement strategies should target patients with atypical small acinar proliferation and high grade prostatic intraepithelial neoplasia as they have the highest likelihood of cancer detection. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Localised carcinoma of the prostate: a paradigm of uncertainty.

PubMed Central

Sandhu, S. S.; Kaisary, A. V.

1997-01-01

The incidence and prevalence of prostate cancer is increasing. A number of aetiological factors including age, race, family history and diet have been implicated. The majority of patients present with disease which is amenable only to palliation. Digital rectal examination, serum prostate-specific antigen and transrectal ultrasound can lead to a prostatic biopsy. Transrectal ultrasound, magnetic resonance imaging, bone scan and a chest X-ray are used for staging. The management of localised cancer is shrouded in uncertainty. Three options exist, watchful waiting, radiotherapy, and radical total prostatectomy. The published data are inadequate for a valid comparison of these, and none has been shown to offer an advantage. Surgery, and to a lesser degree radiotherapy, have a significant morbidity. It is hoped that through better understanding our management of this disease will improve. Images Figure 1 Figure 2 Figure 33 PMID:9519179

Early prostate cancer antigen expression in predicting presence of prostate cancer in men with histologically negative biopsies.

PubMed

Hansel, D E; DeMarzo, A M; Platz, E A; Jadallah, S; Hicks, J; Epstein, J I; Partin, A W; Netto, G J

2007-05-01

Early prostate cancer antigen is a nuclear matrix protein that was recently shown to be expressed in prostate adenocarcinoma and adjacent benign tissue. Previous studies have demonstrated early prostate cancer antigen expression in benign prostate tissue up to 5 years before a diagnosis of prostate carcinoma, suggesting that early prostate cancer antigen could be used as a potential predictive marker. We evaluated early prostate cancer antigen expression by immunohistochemistry using a polyclonal antibody (Onconome Inc., Seattle, Washington) on benign biopsies from 98 patients. Biopsies were obtained from 4 groups that included 39 patients with first time negative biopsy (group 1), 24 patients with persistently negative biopsies (group 2), 8 patients with initially negative biopsies who were subsequently diagnosed with prostate carcinoma (group 3) and negative biopsies obtained from 27 cases where other concurrent biopsies contained prostate carcinoma (group 4). Early prostate cancer antigen staining was assessed by 2 of the authors who were blind to the group of the examined sections. Staining intensity (range 0 to 3) and extent (range 1 to 3) scores were assigned. The presence of intensity 3 staining in any of the blocks of a biopsy specimen was considered as positive for early prostate cancer antigen for the primary outcome in the statistical analysis. In addition, as secondary outcomes we evaluated the data using the proportion of blocks with intensity 3 early prostate cancer antigen staining, the mean of the product of staining intensity and staining extent of all blocks within a biopsy, and the mean of the product of intensity 3 staining and extent. Primary outcome analysis revealed the proportion of early prostate cancer antigen positivity to be highest in group 3 (6 of 8, 75%) and lowest in group 2 (7 of 24, 29%, p=0.04 for differences among groups). A relatively higher than expected proportion of early prostate cancer antigen positivity was present in group 1 (23 of 39, 59%). Early prostate cancer antigen was negative in 41% of group 4 who were known to harbor prostate carcinoma. The proportion of early prostate cancer antigen positivity was statistically significantly lower in group 2 than in each of the other groups when compared pairwise. A lower proportion of early prostate cancer antigen positivity was encountered in older archival tissue blocks (p<0.0001) pointing to a potential confounding factor. Corrected for block age, group 3 was the only group to remain statistically significantly different in early prostate cancer antigen positivity compared to the reference group 2. Similar findings were obtained when adjustments for patient age were made and when analysis was based on secondary outcome measurements. Our study showed a higher proportion of early prostate cancer antigen expression in initial negative prostate biopsy of patients who were diagnosed with prostate carcinoma on subsequent followup biopsies. We found a relatively high proportion of early prostate cancer antigen positivity (59%) in the group with first time negative biopsies and a potential 41% rate of false-negative early prostate cancer antigen staining in benign biopsies from cases with documented prostate carcinoma on concurrent cores. The lower early prostate cancer antigen positivity in cases with older blocks raises the question of a confounding effect of block age. Additional studies on the antigenic properties of early prostate cancer antigen in archival material are required to further delineate the usefulness of early prostate cancer antigen immunostaining on biopsy material.

The rupture and repair of the couple's communal body with prostate cancer.

PubMed

Fergus, Karen D

2011-06-01

Intimate partners' ability to adopt a "we" outlook in relation to cancer has consistently been associated with optimal adaptation for couples. This investigation adds to the growing body of literature on dyadic coping and resiliency in couples through an in-depth examination of five well-adjusted couples' experiences with prostate cancer. Of specific interest were (1) how the experience of prostate cancer affected the couple's unique intersubjective identity, and how in turn (2) the couple's identity and relationship culture influenced their adjustment to cancer. An ethnographic mode of inquiry was adopted. Marital partners were interviewed together on two separate occasions with the intention of having them deepen their conjoint reflexive processing of their relationship. During the interviews, couples were asked to reflect upon and articulate their sense of themselves as a couple, their experience of "we-ness" and shared identity, and the interaction between the illness and we-ness. Interviews were transcribed verbatim and analyzed using the grounded theory method. The grounded theory analysis yielded three main themes portraying the couples' experience of prostate cancer: (1) riding the vortex, (2) holding the communal body intact, and (3) invincibility and its underbelly. A more broad understanding to arise from this investigation was the notion of a "communal body" and that couples participated in a shared corporeality, to which each partner's identity and sense of self was intricately tied. It is concluded that the intersubjective embodiment displayed by couples in this study was instrumental to the "repair" of the communal body ruptured by prostate cancer. ©2011 APA

Is there a link between BPH and prostate cancer?

PubMed

Chang, R T M; Kirby, Roger; Challacombe, B J

2012-04-01

BPH is one of the most common diseases of older men, with more than 70% of men over 70 years affected, and prostate cancer is the most common cancer in men in the UK. Prostate cancer generally presents in one of three ways: asymptomatic patients who are screened (usually by a PSA test); men with LUTS who are investigated and undergo prostate biopsy; or patients with symptoms of metastasis such as bone pain. Men can be reassured that the main cause of LUTS is BPH. Only a small proportion of men have LUTS that are directly attributable to prostate cancer. Digital rectal examination (DRE) gives an evaluation of prostate size, which is relevant in particular to BPH management, and along with PSA testing it is one of the only ways of differentiating clinically between BPH and prostate cancer. If a nodular abnormality is present there is around a 50% chance of a diagnosis of prostate cancer being made on biopsy. Raised levels of serum PSA may be suggestive of prostate cancer, but diagnosis requires histological confirmation in almost every case. A normal PSA, PSA density and DRE can give reasonable confidence with regards to excluding clinically significant prostate cancer. BPH is not a known risk factor for prostate cancer, although the two frequently coexist. Age is the strongest predictor of prostate cancer risk, along with family history. BPH is not considered to be a precursor of prostate cancer. It is likely that although BPH may not make prostate cancer more likely to occur, it may increase the chance of diagnosing an incidental cancer.

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.

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

Carbon ion irradiation of the human prostate cancer cell line PC3: A whole genome microarray study

PubMed Central

SUETENS, ANNELIES; MOREELS, MARJAN; QUINTENS, ROEL; CHIRIOTTI, SABINA; TABURY, KEVIN; MICHAUX, ARLETTE; GRÉGOIRE, VINCENT; BAATOUT, SARAH

2014-01-01

Hadrontherapy is a form of external radiation therapy, which uses beams of charged particles such as carbon ions. Compared to conventional radiotherapy with photons, the main advantage of carbon ion therapy is the precise dose localization along with an increased biological effectiveness. The first results obtained from prostate cancer patients treated with carbon ion therapy showed good local tumor control and survival rates. In view of this advanced treatment modality we investigated the effects of irradiation with different beam qualities on gene expression changes in the PC3 prostate adenocarcinoma cell line. For this purpose, PC3 cells were irradiated with various doses (0.0, 0.5 and 2.0 Gy) of carbon ions (LET=33.7 keV/μm) at the beam of the Grand Accélérateur National d’Ions Lourds (Caen, France). Comparative experiments with X-rays were performed at the Belgian Nuclear Research Centre. Genome-wide gene expression was analyzed using microarrays. Our results show a downregulation in many genes involved in cell cycle and cell organization processes after 2.0 Gy irradiation. This effect was more pronounced after carbon ion irradiation compared with X-rays. Furthermore, we found a significant downregulation of many genes related to cell motility. Several of these changes were confirmed using qPCR. In addition, recurrence-free survival analysis of prostate cancer patients based on one of these motility genes (FN1) revealed that patients with low expression levels had a prolonged recurrence-free survival time, indicating that this gene may be a potential prognostic biomarker for prostate cancer. Understanding how different radiation qualities affect the cellular behavior of prostate cancer cells is important to improve the clinical outcome of cancer radiation therapy. PMID:24504141

Role of androgen and vitamin D receptors in endothelial cells from benign and malignant human prostate

PubMed Central

Chung, Ivy; Montecinos, Viviana P.; Buttyan, Ralph; Johnson, Candace S.; Smith, Gary J.

2013-01-01

Forty years ago, Judah Folkman (Folkman. N Engl J Med 285: 1182–1186, 1971) proposed that tumor growth might be controlled by limiting formation of new blood vessels (angiogenesis) needed to supply a growing tumor with oxygen and nutrients. To this end, numerous “antiangiogenic” agents have been developed and tested for therapeutic efficacy in cancer patients, including prostate cancer (CaP) patients, with limited success. Despite the lack of clinical efficacy of lead anti-angiogenic therapeutics in CaP patients, recent published evidence continues to support the idea that prostate tumor vasculature provides a reasonable target for development of new therapeutics. Particularly relevant to antiangiogenic therapies targeted to the prostate is the observation that specific hormones can affect the survival and vascular function of prostate endothelial cells within normal and malignant prostate tissues. Here, we review the evidence demonstrating that both androgen(s) and vitamin D significantly impact the growth and survival of endothelial cells residing within prostate cancer and that systemic changes in circulating androgen or vitamin D drastically affect blood flow and vascularity of prostate tissue. Furthermore, recent evidence will be discussed about the expression of the receptors for both androgen and vitamin D in prostate endothelial cells that argues for direct effects of these hormone-activated receptors on the biology of endothelial cells. Based on this literature, we propose that prostate tumor vasculature represents an unexplored target for modulation of tumor growth. A better understanding of androgen and vitamin D effects on prostate endothelial cells will support development of more effective angiogenesis-targeting therapeutics for CaP patients. PMID:23548616

Co-Expression of Putative Cancer Stem Cell Markers CD44 and CD133 in Prostate Carcinomas.

PubMed

Kalantari, Elham; Asgari, Mojgan; Nikpanah, Seyedehmoozhan; Salarieh, Naghme; Asadi Lari, Mohammad Hossein; Madjd, Zahra

2017-10-01

Cancer stem cells (CSCs) are the main players of prostate tumorigenesis thus; characterization of CSCs can pave the way for understanding the early detection, drug resistance, metastasis and relapse. The current study was conducted to evaluate the expression level and clinical significance of the potential CSC markers CD44 and CD133 in a series of prostate tissues. One hundred and forty eight prostate tissues composed of prostate cancer (PCa), high-grade prostatic intraepithelial neoplasia (HGPIN), and benign prostate hyperplasia (BPH) were immunostained for the putative CSC markers CD44 and CD133. Subsequently, the correlation between the expression of these markers and the clinicopathological variables was examined. A higher level of CD44 expression was observed in 42% of PCa, 57% of HGPIN, and 42% BPH tissues. In the case of CD133 expression PCa, HGPIN, and BPH samples demonstrated high immunoreactivity in 46%, 43%, and 42% of cells, respectively. Statistical analysis showed an inverse significant correlation between CD44 expression with Gleason score of PCa (P = 0.02), while no significant correlation was observed between CD133 expression and clinicopathological parameters. A significant reciprocal correlation was observed between the expression of two putative CSC markers CD44 and CD133 in PCa specimens while not indicating clinical significance. Further clinical investigation is required to consider these markers as targets of new therapeutic strategies for PCa.

PI3Kbeta Inhibitor AZD8186 and Docetaxel in Treating Patients Advanced Solid Tumors With PTEN or PIK3CB Mutations That Are Metastatic or Cannot Be Removed by Surgery

ClinicalTrials.gov

2018-05-16

Advanced Malignant Solid Neoplasm; Anatomic Stage III Breast Cancer AJCC v8; Anatomic Stage IIIA Breast Cancer AJCC v8; Anatomic Stage IIIB Breast Cancer AJCC v8; Anatomic Stage IIIC Breast Cancer AJCC v8; Anatomic Stage IV Breast Cancer AJCC v8; Castration-Resistant Prostate Carcinoma; Estrogen Receptor Negative; Estrogen Receptor Positive; HER2/Neu Negative; Metastatic Malignant Solid Neoplasm; Metastatic Prostate Carcinoma; PIK3CB Gene Mutation; Progesterone Receptor Negative; Prognostic Stage III Breast Cancer AJCC v8; Prognostic Stage IIIA Breast Cancer AJCC v8; Prognostic Stage IIIB Breast Cancer AJCC v8; Prognostic Stage IIIC Breast Cancer AJCC v8; Prognostic Stage IV Breast Cancer AJCC v8; PTEN Gene Mutation; PTEN Loss; Stage III Prostate Cancer AJCC v8; Stage IIIA Prostate Cancer AJCC v8; Stage IIIB Prostate Cancer AJCC v8; Stage IIIC Prostate Cancer AJCC v8; Stage IV Prostate Cancer AJCC v8; Stage IVA Prostate Cancer AJCC v8; Stage IVB Prostate Cancer AJCC v8; Triple-Negative Breast Carcinoma; Unresectable Solid Neoplasm

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.

Transcription factor Stat5a/b as a therapeutic target protein for prostate cancer

PubMed Central

Liao, Zhiyong; Lutz, Jacqueline; Nevalainen, Marja T.

2009-01-01

Prostate cancer is the most common non-cutaneous cancer in Western males. The majority of prostate cancer fatalities are caused by development of castration-resistant growth and metastatic spread of the primary tumor. The average duration of the response of primary prostate cancer to hormonal ablation is less than 3 years, and 75% of prostate cancers in the United States progress to hormone-refractory disease. The existing pharmacological therapies for metastatic and/or hormone-refractory prostate cancer do not provide significant survival benefit. This review summarizes the importance of transcription factor Stat5 signaling in the pathogenesis of prostate cancer and discusses the molecular basis why inhibition of Stat5a/b could be used as a therapeutic strategy for prostate cancer. PMID:19914392

6 Common Cancers - Prostate Cancer

MedlinePlus

... Bar Home Current Issue Past Issues 6 Common Cancers - Prostate Cancer Past Issues / Spring 2007 Table of Contents For ... early screening. Photo: AP Photo/Danny Moloshok Prostate Cancer The prostate gland is a walnut-sized structure ...

Pomegranate-Extract Pill in Preventing Tumor Growth in Patients With Localized Prostate Cancer Undergoing Active Surveillance

ClinicalTrials.gov

2018-03-02

PSA Level Less Than or Equal to Fifteen; PSA Level Less Than Ten; Stage I Prostate Cancer AJCC v7; Stage II Prostate Cancer AJCC v7; Stage IIA Prostate Cancer AJCC v7; Stage IIB Prostate Cancer AJCC v7

3 CFR 8408 - Proclamation 8408 of August 31, 2009. National Prostate Cancer Awareness Month, 2009

Code of Federal Regulations, 2010 CFR

2010-01-01

... Prostate Cancer Awareness Month, 2009 8408 Proclamation 8408 Presidential Documents Proclamations Proclamation 8408 of August 31, 2009 Proc. 8408 National Prostate Cancer Awareness Month, 2009By the President... fight against prostate cancer. Over the last decade, prostate cancer mortality rates have fallen...

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.

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.

CD8+ T-cell responses rapidly select for antigen-negative tumor cells in the prostate.

PubMed

Bak, S Peter; Barnkob, Mike Stein; Wittrup, K Dane; Chen, Jianzhu

2013-12-01

Stimulation of patients' immune systems for the treatment of solid tumors is an emerging therapeutic paradigm. The use of enriched autologous T cells for adoptive cell therapy or vaccination with antigen-loaded dendritic cells have shown clinical efficacy in melanoma and prostate cancer, respectively. However, the long-term effects of immune responses on selection and outgrowth of antigen-negative tumor cells in specific tumor types must be determined to understand and achieve long-term therapeutic effects. In this study, we have investigated the expression of a tumor-specific antigen in situ after treatment with tumor-specific CD8(+) T cells in an autochthonous mouse model of prostate cancer. After T-cell treatment, aggregates of dead antigen-positive tumor cells were concentrated in the lumen of the prostate gland and were eventually eliminated from the prostate tissue. Despite the elimination of antigen-positive tumor cells, prostate tumor continued to grow in T-cell-treated mice. Interestingly, the remaining tumor cells were antigen negative and downregulated MHC class I expression. These results show that CD8(+) T cells are effective in eliminating antigen-bearing prostate tumor cells but they also can select for the outgrowth of antigen-negative tumor cells. These findings provide insights into the requirements for an effective cancer immunotherapy within the prostate that not only induces potent immune responses but also avoids selection and outgrowth of antigen-negative tumor cells. ©2013 AACR.

Targeting Btk/Etk of prostate cancer cells by a novel dual inhibitor

PubMed Central

Guo, W; Liu, R; Bhardwaj, G; Yang, J C; Changou, C; Ma, A-H; Mazloom, A; Chintapalli, S; Xiao, K; Xiao, W; Kumaresan, P; Sanchez, E; Yeh, C-T; Evans, C P; Patterson, R; Lam, K S; Kung, H-J

2014-01-01

Btk and Etk/BMX are Tec-family non-receptor tyrosine kinases. Btk has previously been reported to be expressed primarily in B cells and has an important role in immune responses and B-cell malignancies. Etk has been shown previously to provide a strong survival and metastasis signal in human prostate cancer cells, and to confer androgen independence and drug resistance. While the role of Etk in prostate carcinogenesis is well established, the functions of Btk in prostate cancer have never been investigated, likely due to the perception that Btk is a hematopoietic, but not epithelial, kinase. Herein, we found that Btk is overexpressed in prostate cancer tissues and prostate cancer cells. The level of Btk in prostate cancer tissues correlates with cancer grades. Knockdown of Btk expression selectively inhibits the growth of prostate cancer cells, but not that of the normal prostate epithelial cells, which express very little Btk. Dual inhibition of Btk and Etk has an additive inhibitory effect on prostate cancer cell growth. To explore Btk and Etk as targets for prostate cancer, we developed a small molecule dual inhibitor of Btk and Etk, CTN06. Treatment of PC3 and other prostate cancer cells, but not immortalized prostate epithelial cells with CTN06 resulted in effective cell killing, accompanied by the attenuation of Btk/Etk signals. The killing effect of CTN06 is more potent than that of commonly used inhibitors against Src, Raf/VEGFR and EGFR. CTN06 induces apoptosis as well as autophagy in human prostate cancer cells, and is a chemo-sensitizer for docetaxel (DTX), a standard of care for metastatic prostate cancer patients. CTN06 also impeded the migration of human prostate cancer cells based on a ‘wound healing' assay. The anti-cancer effect of CTN06 was further validated in vivo in a PC3 xenograft mouse model. PMID:25188519

Targeting Btk/Etk of prostate cancer cells by a novel dual inhibitor.

PubMed

Guo, W; Liu, R; Bhardwaj, G; Yang, J C; Changou, C; Ma, A-H; Mazloom, A; Chintapalli, S; Xiao, K; Xiao, W; Kumaresan, P; Sanchez, E; Yeh, C-T; Evans, C P; Patterson, R; Lam, K S; Kung, H-J

2014-09-04

Btk and Etk/BMX are Tec-family non-receptor tyrosine kinases. Btk has previously been reported to be expressed primarily in B cells and has an important role in immune responses and B-cell malignancies. Etk has been shown previously to provide a strong survival and metastasis signal in human prostate cancer cells, and to confer androgen independence and drug resistance. While the role of Etk in prostate carcinogenesis is well established, the functions of Btk in prostate cancer have never been investigated, likely due to the perception that Btk is a hematopoietic, but not epithelial, kinase. Herein, we found that Btk is overexpressed in prostate cancer tissues and prostate cancer cells. The level of Btk in prostate cancer tissues correlates with cancer grades. Knockdown of Btk expression selectively inhibits the growth of prostate cancer cells, but not that of the normal prostate epithelial cells, which express very little Btk. Dual inhibition of Btk and Etk has an additive inhibitory effect on prostate cancer cell growth. To explore Btk and Etk as targets for prostate cancer, we developed a small molecule dual inhibitor of Btk and Etk, CTN06. Treatment of PC3 and other prostate cancer cells, but not immortalized prostate epithelial cells with CTN06 resulted in effective cell killing, accompanied by the attenuation of Btk/Etk signals. The killing effect of CTN06 is more potent than that of commonly used inhibitors against Src, Raf/VEGFR and EGFR. CTN06 induces apoptosis as well as autophagy in human prostate cancer cells, and is a chemo-sensitizer for docetaxel (DTX), a standard of care for metastatic prostate cancer patients. CTN06 also impeded the migration of human prostate cancer cells based on a 'wound healing' assay. The anti-cancer effect of CTN06 was further validated in vivo in a PC3 xenograft mouse model.

Cysteine-rich secretory protein 3 plays a role in prostate cancer cell invasion and affects expression of PSA and ANXA1.

PubMed

Pathak, Bhakti R; Breed, Ananya A; Apte, Snehal; Acharya, Kshitish; Mahale, Smita D

2016-01-01

Cysteine-rich secretory protein 3 (CRISP-3) is upregulated in prostate cancer as compared to the normal prostate tissue. Higher expression of CRISP-3 has been linked to poor prognosis and hence it has been thought to act as a prognostic marker for prostate cancer. It is proposed to have a role in innate immunity but its role in prostate cancer is still unknown. In order to understand its function, its expression was stably knocked down in LNCaP cells. CRISP-3 knockdown did not affect cell viability but resulted in reduced invasiveness. Global gene expression changes upon CRISP-3 knockdown were identified by microarray analysis. Microarray data were quantitatively validated by evaluating the expression of seven candidate genes in three independent stable clones. Functional annotation of the differentially expressed genes identified cell adhesion, cell motility, and ion transport to be affected among other biological processes. Prostate-specific antigen (PSA, also known as Kallikrein 3) was the top most downregulated gene whose expression was also validated at protein level. Interestingly, expression of Annexin A1 (ANXA1), a known anti-inflammatory protein, was upregulated upon CRISP-3 knockdown. Re-introduction of CRISP-3 into the knockdown clone reversed the effect on invasiveness and also led to increased PSA expression. These results suggest that overexpression of CRISP-3 in prostate tumor may maintain higher PSA expression and lower ANXA1 expression. Our data also indicate that poor prognosis associated with higher CRISP-3 expression could be due to its role in cell invasion.

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

Dietary Lycopene, Angiogenesis, and Prostate Cancer: A Prospective Study in the Prostate-Specific Antigen Era

PubMed Central

2014-01-01

Background The role of lycopene in prostate cancer prevention remains controversial. We examined the associations between dietary lycopene intake and prostate cancer, paying particular attention to the influence of prostate-specific antigen screening, and evaluated tissue biomarkers in prostate cancers in relation to lycopene intake. Methods Among 49898 male health professionals, we obtained dietary information through questionnaires and ascertained total and lethal prostate cancer cases from 1986 through January 31, 2010. Cox regression was used to estimate multivariable hazard ratios (HRs) and 95% confidence intervals (CIs). Tissue microarrays and immunohistochemistry were used to assess tumor biomarker expression in a subset of men. Two-sided χ2 tests were used to calculate the P values. Results Higher lycopene intake was inversely associated with total prostate cancer and more strongly with lethal prostate cancer (top vs bottom quintile: HR = 0.72; 95% CI = 0.56 to 0.94; P trend = .04). In a restricted population of screened participants, the inverse associations became markedly stronger (for lethal prostate cancer: HR = 0.47; 95% CI = 0.29 to 0.75; P trend = .009). Comparing different measures of dietary lycopene, early intake, but not recent intake, was inversely associated with prostate cancer. Higher lycopene intake was associated with biomarkers in the cancer indicative of less angiogenic potential. Conclusions Dietary intake of lycopene was associated with reduced risk of lethal prostate cancer and with a lesser degree of angiogenesis in the tumor. Because angiogenesis is a strong progression factor, an endpoint of lethal prostate cancer may be more relevant than an endpoint of indolent prostate cancer for lycopene in the era of highly prevalent prostate-specific antigen screening. PMID:24463248

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.

Dietary intakes of carbohydrates in relation to prostate cancer risk: a prospective study in the Malmö Diet and Cancer cohort.

PubMed

Drake, Isabel; Sonestedt, Emily; Gullberg, Bo; Ahlgren, Göran; Bjartell, Anders; Wallström, Peter; Wirfält, Elisabet

2012-12-01

Dietary carbohydrates have been implicated in relation to prostate cancer. Our objective was to examine the associations between dietary intakes of carbohydrates, fiber, and their food sources and risk of prostate cancer, overall and by case severity, in the Malmö Diet and Cancer cohort. The analysis included 8128 men aged 45-73 y without a history of cancer, cardiovascular disease, or diabetes and who were classified as adequate energy reporters. After a median follow-up time of 15 y, prostate cancer was diagnosed in 817 men. We used Cox proportional hazards regression to model associations between energy-adjusted nutrient and food intakes with risk of incident prostate cancer, with competing risk of death from non-prostate cancer causes taken into account. After adjustment for age and other known or potential risk factors, we observed no associations between total carbohydrates or dietary fiber and prostate cancer. We observed positive associations between the intake of low-fiber cereals with overall and low-risk prostate cancer and between intakes of cake and biscuits and rice and pasta with low-risk prostate cancer (all P-trend < 0.05). A high intake compared with zero consumption of sugar-sweetened beverages was associated with increased risk of symptomatic prostate cancer (HR: 1.38; 95% CI: 1.04, 1.84). Results from this large study with high-validity dietary data suggest that a high intake of refined carbohydrates may be associated with increased risk of prostate cancer. However we observed no significant associations with high-risk prostate cancer, and not all foods that are typically high in refined carbohydrates were associated with prostate cancer.

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

Association analysis of 9,560 prostate cancer cases from the International Consortium of Prostate Cancer Genetics confirms the role of reported prostate-cancer associated SNPs for familial disease

PubMed Central

Teerlink, Craig C.; Thibodeau, Stephen N.; McDonnell, Shannon K.; Schaid, Daniel J.; Rinckleb, Antje; Maier, Christiane; Vogel, Walther; Cancel-Tassin, Geraldine; Egrot, Christophe; Cussenot, Olivier; Foulkes, William D.; Giles, Graham G.; Hopper, John L.; Severi, Gianluca; Eeles, Ros; Easton, Douglas; Kote-Jarai, Zsofia; Guy, Michelle; Cooney, Kathleen A.; Ray, Anna M.; Zuhlke, Kimberly A.; Lange, Ethan M.; FitzGerald, Liesel M.; Stanford, Janet L.; Ostrander, Elaine A.; Wiley, Kathleen E.; Isaacs, Sarah D.; Walsh, Patrick C.; Isaacs, William B.; Wahlfors, Tiina; Tammela, Teuvo; Schleutker, Johanna; Wiklund, Fredrik; Grönberg, Henrik; Emanuelsson, Monica; Carpten, John; Bailey-Wilson, Joan; Whittemore, Alice S.; Oakley-Girvan, Ingrid; Hsieh, Chih-Lin; Catalona, William J.; Zheng, S. Lilly; Jin, Guangfu; Lu, Lingyi; Xu, Jianfeng; Camp, Nicola J.; Cannon-Albright, Lisa A.

2013-01-01

Previous GWAS studies have reported significant associations between various common SNPs and prostate cancer risk using cases unselected for family history. How these variants influence risk in familial prostate cancer is not well studied. Here, we analyzed 25 previously reported SNPs across 14 loci from prior prostate cancer GWAS. The International Consortium for Prostate Cancer Genetics (ICPCG) previously validated some of these using a family-based association method (FBAT). However, this approach suffered reduced power due to the conditional statistics implemented in FBAT. Here, we use a case-control design with an empirical analysis strategy to analyze the ICPCG resource for association between these 25 SNPs and familial prostate cancer risk. Fourteen sites contributed 12,506 samples (9,560 prostate cancer cases, 3,368 with aggressive disease, and 2,946 controls from 2,283 pedigrees). We performed association analysis with Genie software which accounts for relationships. We analyzed all familial prostate cancer cases and the subset of aggressive cases. For the familial prostate cancer phenotype, 20 of the 25 SNPs were at least nominally associated with prostate cancer and 16 remained significant after multiple testing correction (p≤1E−3) occurring on chromosomal bands 6q25, 7p15, 8q24, 10q11, 11q13, 17q12, 17q24, and Xp11. For aggressive disease, 16 of the SNPs had at least nominal evidence and 8 were statistically significant including 2p15. The results indicate that the majority of common, low-risk alleles identified in GWAS studies for all prostate cancer also contribute risk for familial prostate cancer, and that some may be contribute risk to aggressive disease. PMID:24162621

Estrogen and estrogen receptor alpha promotes malignancy and osteoblastic tumorigenesis in prostate cancer.

PubMed

Mishra, Sweta; Tai, Qin; Gu, Xiang; Schmitz, James; Poullard, Ashley; Fajardo, Roberto J; Mahalingam, Devalingam; Chen, Xiaodong; Zhu, Xueqiong; Sun, Lu-Zhe

2015-12-29

The role of estrogen signaling in regulating prostate tumorigenesis is relatively underexplored. Although, an increasing body of evidence has linked estrogen receptor beta (ERß) to prostate cancer, the function of estrogen receptor alpha (ERα) in prostate cancer is not very well studied. We have discovered a novel role of ERα in the pathogenesis of prostate tumors. Here, we show that prostate cancer cells express ERα and estrogen induces oncogenic properties in prostate cancer cells through ERα. Importantly, ERα knockdown in the human prostate cancer PacMetUT1 cells as well as pharmacological inhibition of ERα with ICI 182,780 inhibited osteoblastic lesion formation and lung metastasis in vivo. Co-culture of pre-osteoblasts with cancer cells showed a significant induction of osteogenic markers in the pre-osteoblasts, which was attenuated by knockdown of ERα in cancer cells suggesting that estrogen/ERα signaling promotes crosstalk between cancer and osteoblastic progenitors to stimulate osteoblastic tumorigenesis. These results suggest that ERα expression in prostate cancer cells is essential for osteoblastic lesion formation and lung metastasis. Thus, inhibition of ERα signaling in prostate cancer cells may be a novel therapeutic strategy to inhibit the osteoblastic lesion development as well as lung metastasis in patients with advanced prostate cancer.

Digoxin and prostate cancer survival in the Finnish Randomized Study of Screening for Prostate Cancer.

PubMed

Kaapu, Kalle J; Murtola, Teemu J; Talala, Kirsi; Taari, Kimmo; Tammela, Teuvo Lj; Auvinen, Anssi

2016-11-22

Protective effects have been suggested for digoxin against prostate cancer risk. However, few studies have evaluated the possible effects on prostate cancer-specific survival. We studied the association between use of digoxin or beta-blocker sotalol and prostate cancer-specific survival as compared with users of other antiarrhythmic drugs in a retrospective cohort study. Our study population consisted of 6537 prostate cancer cases from the Finnish Randomized Study of Screening for Prostate Cancer diagnosed during 1996-2009 (485 digoxin users). The median exposure for digoxin was 480 DDDs (interquartile range 100-1400 DDDs). During a median follow-up of 7.5 years after diagnosis, 617 men (48 digoxin users) died of prostate cancer. We collected information on antiarrhythmic drug purchases from the national prescription database. Both prediagnostic and postdiagnostic drug usages were analysed using the Cox regression method. No association was found for prostate cancer death with digoxin usage before (HR 1.00, 95% CI 0.56-1.80) or after (HR 0.81, 95% CI 0.43-1.51) prostate cancer diagnosis. The results were also comparable for sotalol and antiarrhythmic drugs in general. Among men not receiving hormonal therapy, prediagnostic digoxin usage was associated with prolonged prostate cancer survival (HR 0.20, 95% CI 0.05-0.86). No general protective effects against prostate cancer were observed for digoxin or sotalol usage.

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.

Prevention and Early Detection of Prostate Cancer

PubMed Central

Cuzick, Jack; Thorat, Mangesh A.; Andriole, Gerald; Brawley, Otis W.; Brown, Powel H.; Culig, Zoran; Eeles, Rosalind A.; Ford, Leslie G.; Hamdy, Freddie C.; Holmberg, Lars; Ilic, Dragan; Key, Timothy J.; La Vecchia, Carlo; Lilja, Hans; Marberger, Michael; Meyskens, Frank L.; Minasian, Lori M.; Parker, Chris; Parnes, Howard L.; Perner, Sven; Rittenhouse, Harry; Schalken, Jack; Schmid, Hans-Peter; Schmitz-Dräger, Bernd J.; Schröder, Fritz H.; Stenzl, Arnulf; Tombal, Bertrand; Wilt, Timothy J.; Wolk, Alicja

2014-01-01

Prostate cancer is one of the most common cancers in men and the global burden of this disease is rising. Lifestyle modifications like smoking cessation, exercise and weight control offer opportunities to decrease the risk of developing prostate cancer. Early detection of prostate cancer by PSA screening remains controversial; yet, changes in PSA threshold, frequency of screening, and addition of other biomarkers have potential to minimise overdiagnosis associated with PSA screening. Several new biomarkers appear promising in individuals with elevated PSA levels or those diagnosed with prostate cancer, these are likely to guide in separating individuals who can be spared of aggressive treatment from those who need it. Several pharmacological agents like 5α-reductase inhibitors, aspirin etc. have a potential to prevent development of prostate cancer. In this review, we discuss the current evidence and research questions regarding prevention, early detection of prostate cancer and management of men either at high risk of prostate cancer or diagnosed with low-grade prostate cancer. PMID:25281467

Pomegranate and Its Components as Alternative Treatment for Prostate Cancer

PubMed Central

Wang, Lei; Martins-Green, Manuela

2014-01-01

Prostate cancer is the second leading cause of cancer deaths in men in the United States. There is a major need for less toxic but yet effective therapies to treat prostate cancer. Pomegranate fruit from the tree Punica granatum has been used for centuries for medicinal purposes and is described as “nature’s power fruit”. Recent research has shown that pomegranate juice (PJ) and/or pomegranate extracts (PE) significantly inhibit the growth of prostate cancer cells in culture. In preclinical murine models, PJ and/or PE inhibit growth and angiogenesis of prostate tumors. More recently, we have shown that three components of PJ, luteolin, ellagic acid and punicic acid together, have similar inhibitory effects on prostate cancer growth, angiogenesis and metastasis. Results from clinical trials are also promising. PJ and/or PE significantly prolonged the prostate specific antigen (PSA) doubling time in patients with prostate cancer. In this review we discuss data on the effects of PJ and PE on prostate cancer. We also discuss the effects of specific components of the pomegranate fruit and how they have been used to study the mechanisms involved in prostate cancer progression and their potential to be used in deterring prostate cancer metastasis. PMID:25158234

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

β-carotene 9’,10’ oxygenase Modulates the Anticancer Activity of Dietary Tomato or Lycopene on Prostate Carcinogenesis in the TRAMP Model

PubMed Central

Tan, Hsueh-Li; Thomas-Ahner, Jennifer M.; Moran, Nancy E.; Cooperstone, Jessica L.; Erdman, John W.; Young, Gregory S.; Clinton, Steven K.

2017-01-01

The hypothesis that dietary tomato consumption or the intake of the carotenoid lycopene inhibits prostate cancer arose from epidemiologic studies and is supported by preclinical rodent experiments and in vitro mechanistic studies. We hypothesize that variation in activity of carotenoid cleavage enzymes, such as β-carotene 9’,10’-oxygenase (BCO2), may alter the impact of dietary tomato and lycopene on prostate carcinogenesis and therefore examined this relationship in the TRAMP model. Starting at three weeks of age, TRAMP:Bco2+/+ and TRAMP:Bco2−/− mice were fed either AIN-93G control, or semi-purified diets containing 10% tomato powder or 0.25% lycopene beadlets until 18 weeks of age. Both tomato- and lycopene-fed TRAMP:Bco2−/− mice had significantly greater serum concentrations of total, 5-cis, other cis, and all-trans lycopene than TRAMP:Bco2+/+ mice. Tomato- and lycopene-fed mice had a lower incidence of prostate cancer compared to the control-fed mice. While Bco2 genotype alone did not significantly change prostate cancer outcome in the control AIN-93G-fed mice, the abilities of lycopene and tomato feeding to inhibit prostate carcinogenesis were significantly attenuated by the loss of Bco2 (interaction p=0.0004 and p=0.0383, respectively). Overall, dietary tomato and lycopene inhibited the progression of prostate cancer in TRAMP in a Bco2 genotype-specific manner, potentially implicating the anticancer activity of lycopene cleavage products. This study suggests that genetic variables impacting carotenoid metabolism and accumulation can impact anti-cancer activity and that future efforts devoted to understanding the interface between tomato carotenoid intake, host genetics, and metabolism will be necessary to clearly elucidate their interactive roles in human prostate carcinogenesis. PMID:27807077

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.

A novel canine model for prostate cancer.

PubMed

Keller, Jill M; Schade, George R; Ives, Kimberly; Cheng, Xu; Rosol, Thomas J; Piert, Morand; Siddiqui, Javed; Roberts, William W; Keller, Evan T

2013-06-01

No existing animal model fully recapitulates all features of human prostate cancer. The dog is the only large mammal, besides humans, that commonly develops spontaneous prostate cancer. Canine prostate cancer features many similarities with its human counterpart. We sought to develop a canine model of prostate cancer that would more fully represent the features of human prostate cancer than existing models. The Ace-1 canine prostate cancer cell line was injected transabdominally under transrectal ultrasound (TRUS) guidance into the prostates of immunosuppressed, intact, adult male dogs. Tumor progression was monitored by TRUS imaging. Some dogs were subjected to positron emission tomography (PET) for tumor detection. Time of euthanasia was determined based on tumor size, impingement on urethra, and general well-being. Euthanasia was followed by necropsy and histopathology. Ace-1 tumor cells grew robustly in every dog injected. Tumors grew in subcapsular and parenchymal regions of the prostate. Tumor tissue could be identified using PET. Histological findings were similar to those observed in human prostate cancer. Metastases to lungs and lymph nodes were detected, predominantly in dogs with intraprostatic tumors. We have established a minimally invasive dog model of prostate cancer. This model may be valuable for studying prostate cancer progression and distant metastasis. Copyright © 2013 Wiley Periodicals, Inc.

Phospholipase PLA2G7, associated with aggressive prostate cancer, promotes prostate cancer cell migration and invasion and is inhibited by statins

PubMed Central

Vainio, Paula; Lehtinen, Laura; Mirtti, Tuomas; Hilvo, Mika; Seppänen-Laakso, Tuulikki; Virtanen, Johannes; Sankila, Anna; Nordling, Stig; Lundin, Johan; Rannikko, Antti; Orešič, Matej; Kallioniemi, Olli; Iljin, Kristiina

2011-01-01

Prostate cancer is the second leading cause of cancer mortality in men in developed countries. Due to the heterogeneous nature of the disease, design of novel personalized treatments is required to achieve efficient therapeutic responses. We have recently identified phospholipase 2 group VII (PLA2G7) as a potential drug target especially in ERG oncogene positive prostate cancers. Here, the expression profile of PLA2G7 was studied in 1137 prostate cancer and 409 adjacent non-malignant prostate tissues using immunohistochemistry to validate its biomarker potential and putative association with disease progression. In order to reveal the molecular alterations induced by PLA2G7 impairment, lipidomic and gene expression profiling was performed in response to PLA2G7 silencing in cultured prostate cancer cells. Moreover, the antineoplastic effect of statins combined with PLA2G7 impairment was studied in prostate cancer cells to evaluate the potential of repositioning of in vivo compatible drugs developed for other indications towards anti-cancer purposes. The results indicated that PLA2G7 is a cancer-selective biomarker in 50% of prostate cancers and associates with aggressive disease. The alterations induced by PLA2G7 silencing highlighted the potential of PLA2G7 inhibition as an anti-proliferative, pro-apoptotic and anti-migratorial therapeutic approach in prostate cancer. Moreover, the anti-proliferative effect of PLA2G7 silencing was potentiated by lipid-lowering statins in prostate cancer cells. Taken together, our results support the potential of PLA2G7 as a biomarker and a drug target in prostate cancer and present a rationale for combining PLA2G7 inhibition with the use of statins in prostate cancer management. PMID:22202492

A multimedia interactive education system for prostate cancer patients: development and preliminary evaluation.

PubMed

Diefenbach, Michael A; Butz, Brian P

2004-01-21

A cancer diagnosis is highly distressing. Yet, to make informed treatment choices patients have to learn complicated disease and treatment information that is often fraught with medical and statistical terminology. Thus, patients need accurate and easy-to-understand information. To introduce the development and preliminary evaluation through focus groups of a novel highly-interactive multimedia-education software program for patients diagnosed with localized prostate cancer. The prostate interactive education system uses the metaphor of rooms in a virtual health center (ie, reception area, a library, physician offices, group meeting room) to organize information. Text information contained in the library is tailored to a person's information-seeking preference (ie, high versus low information seeker). We conducted a preliminary evaluation through 5 separate focus groups with prostate cancer survivors (N = 18) and their spouses (N = 15). Focus group results point to the timeliness and high acceptability of the software among the target audience. Results also underscore the importance of a guide or tutor who assists in navigating the program and who responds to queries to facilitate information retrieval. Focus groups have established the validity of our approach and point to new directions to further enhance the user interface.

Tweeting About Prostate and Testicular Cancers: What Are Individuals Saying in Their Discussions About the 2013 Movember Canada Campaign?

PubMed

Bravo, Caroline A; Hoffman-Goetz, Laurie

2016-09-01

Effective and persuasive health campaigns are an important tool for promoting cancer prevention education. The 2013 Movember Canada campaign presented an opportunity to raise awareness and funds about men's health with a particular focus on prostate and testicular cancers. The Movember campaign encouraged participants to talk about men's health (including prostate and testicular cancers) and had a strong presence on social media sites such as Twitter in November 2013. The objective of this study was to analyze tweets about the 2013 Movember Canada for underlying themes in order understand what those discussions were about. A directed content analysis methodology was used to analyze 2400 tweets. Tweets were read and coded for overt and latent themes in an iterative fashion until saturation of themes occurred. The major themes identified in the tweets were fundraising as a priority (34 %), making a change to men's health (18 %), the campaign as a moustache contest rather than a charity (26 %), the use of masculine metaphors/imagery (9 %), and the role of women as moustache supporters (4 %). Findings from Twitter suggest that users rarely associate their campaign efforts with prostate and/or testicular cancer in public online conversations about the 2013 Movember Canada campaign.

Overexpression and knock-down studies highlight that a disintegrin and metalloproteinase 28 controls proliferation and migration in human prostate cancer.

PubMed

Rudnicka, Caroline; Mochizuki, Satsuki; Okada, Yasunori; McLaughlin, Claire; Leedman, Peter J; Stuart, Lisa; Epis, Michael; Hoyne, Gerard; Boulos, Sherif; Johnson, Liam; Schlaich, Markus; Matthews, Vance

2016-10-01

Prostate cancer is one of the most prevalent cancers in men. It is critical to identify and characterize oncogenes that drive the pathogenesis of human prostate cancer. The current study builds upon previous research showing that a disintegrin and metallproteinase (ADAM)28 is involved in the pathogenesis of numerous cancers. Our novel study used overexpression, pharmacological, and molecular approaches to investigate the biological function of ADAM28 in human prostate cancer cells, with a focus on cell proliferation and migration. The results of this study provide important insights into the role of metalloproteinases in human prostate cancer.The expression of ADAM28 protein levels was assessed within human prostate tumors and normal adjacent tissue by immunohistochemistry. Immunocytochemistry and western blotting were used to assess ADAM28 protein expression in human prostate cancer cell lines. Functional assays were conducted to assess proliferation and migration in human prostate cancer cells in which ADAM28 protein expression or activity had been altered by overexpression, pharmacological inhibition, or by siRNA gene knockdown.The membrane bound ADAM28 was increased in human tumor biopsies and prostate cancer cell lines. Pharmacological inhibition of ADAM28 activity and/or knockdown of ADAM28 significantly reduced proliferation and migration of human prostate cancer cells, while overexpression of ADAM28 significantly increased proliferation and migration.ADAM28 is overexpressed in primary human prostate tumor biopsies, and it promotes human prostate cancer cell proliferation and migration. This study supports the notion that inhibition of ADAM28 may be a potential novel therapeutic strategy for human prostate cancer.

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

Male sexuality in theory and practice.

PubMed

Kelly, Daniel

2004-06-01

Male sexuality is a complex phenomenon shaped by personal, cultural,and social factors. This article has argued that male sexual function is an important consideration in conditions such as prostate cancer. There are surely other conditions where it is understood even more poorly. Although theorists tend to explore male sexuality in relation to vague concepts such as power, phallocentrism, and aggression, sexuality becomes a personal reality in illness contexts. Using insights from a study into prostate cancer, it has been suggested that men assess embodied risks, such as impotence, in highly individual ways. The uncertainty that characterizes this cancer further compounds the difficulties involved, despite attempts of professionals to provide adequate levels of information and support. Researchers and practitioners alike should begin to question the gap between theoretical constructions of male sexuality and its reality in healthcare situations. More attention should be paid to understanding the importance of sexual function for men who are living with conditions such as prostate cancer. Those men who face up to the threat of such embodied changes, and who learn to cope with physical and emotional (and sexual) vulnerability, may learn to evaluate their lives in new ways. As Kenneth, one of the participants in this study said of his experience of cancer, "It just seems unnecessary for them to have to go through that to learn and understand themselves and be honest with themselves about what is really important."

Local radiotherapy increases the level of autoantibodies to ribosomal P0 protein but not to heat shock proteins, extracellular matrix molecules and EGFR/ErbB2 receptors in prostate cancer patients.

PubMed

Ingrosso, Gianluca; Fantini, Massimo; Nardi, Alessandra; Benvenuto, Monica; Sacchetti, Pamela; Masuelli, Laura; Ponti, Elisabetta; Frajese, Giovanni Vanni; Lista, Florigio; Schillaci, Orazio; Santoni, Riccardo; Modesti, Andrea; Bei, Roberto

2013-03-01

Prostate cancer is a common cancer among men in developed countries. Although hormonotherapy and radiotherapy (RT) represent valid therapies for prostate cancer treatment, novel immunological approaches have been explored. The development of clinical trials employing cancer vaccines has indicated that immune response to tumor antigens can be boosted and that vaccine administration can improve patient survival. Immune response to tumor antigens could also be enhanced after standard therapies. In the present study, we determined the occurrence of antibodies to extracellular matrix (ECM) molecules, heat shock protein (HSP), ribosomal P0 protein, EGFR, ErbB2 and prostate-specific antigen (PSA) in 35 prostate cancer patients prior to and following local RT and hormonotherapy. We demonstrated that immunity to P0, ECM molecules [collagens (C) CI, CIII, CV, fibronectin (FN) and laminin (LM)] and to HSP90 was associated with malignancy in untreated patients. None of the patient sera showed antibodies to EGFR, while 2 and 1 patients showed reactivity to ErbB2 and PSA, respectively. We also demonstrated that 8 months after therapy the IgG serum levels to CI, CIII, FN and HSP90 significantly decreased. Conversely, the level of P0 autoantibodies increased after therapy in 10 patients. Five of the 10 patients with increased levels of P0 autoantibodies were treated with RT plus hormonotherapy. Treatment of patients did not change the levels of antibodies against EGFR, ErbB2 and PSA. Our results indicated that the modification of antibody level to self molecules after standard treatment of prostate cancer patients is influenced by the type of antigen. Ribosomal P0 protein appears to be a high immunogenic antigen and its immunogenicity increases following RT. In addition, 10 patients with increased levels of autoantibodies to P0 showed PSA mean levels lower than the remaining 25 patients at 18 months. This study may contribute to a better understanding of the immunobiological behavior of prostate cancer patients following standard treatment.

Definition of molecular determinants of prostate cancer cell bone extravasation.

PubMed

Barthel, Steven R; Hays, Danielle L; Yazawa, Erika M; Opperman, Matthew; Walley, Kempland C; Nimrichter, Leonardo; Burdick, Monica M; Gillard, Bryan M; Moser, Michael T; Pantel, Klaus; Foster, Barbara A; Pienta, Kenneth J; Dimitroff, Charles J

2013-01-15

Advanced prostate cancer commonly metastasizes to bone, but transit of malignant cells across the bone marrow endothelium (BMEC) remains a poorly understood step in metastasis. Prostate cancer cells roll on E-selectin(+) BMEC through E-selectin ligand-binding interactions under shear flow, and prostate cancer cells exhibit firm adhesion to BMEC via β1, β4, and αVβ3 integrins in static assays. However, whether these discrete prostate cancer cell-BMEC adhesive contacts culminate in cooperative, step-wise transendothelial migration into bone is not known. Here, we describe how metastatic prostate cancer cells breach BMEC monolayers in a step-wise fashion under physiologic hemodynamic flow. Prostate cancer cells tethered and rolled on BMEC and then firmly adhered to and traversed BMEC via sequential dependence on E-selectin ligands and β1 and αVβ3 integrins. Expression analysis in human metastatic prostate cancer tissue revealed that β1 was markedly upregulated compared with expression of other β subunits. Prostate cancer cell breaching was regulated by Rac1 and Rap1 GTPases and, notably, did not require exogenous chemokines as β1, αVβ3, Rac1, and Rap1 were constitutively active. In homing studies, prostate cancer cell trafficking to murine femurs was dependent on E-selectin ligand, β1 integrin, and Rac1. Moreover, eliminating E-selectin ligand-synthesizing α1,3 fucosyltransferases in transgenic adenoma of mouse prostate mice dramatically reduced prostate cancer incidence. These results unify the requirement for E-selectin ligands, α1,3 fucosyltransferases, β1 and αVβ3 integrins, and Rac/Rap1 GTPases in mediating prostate cancer cell homing and entry into bone and offer new insight into the role of α1,3 fucosylation in prostate cancer development.

A genome-wide pleiotropy scan for prostate cancer risk.

PubMed

Panagiotou, Orestis A; Travis, Ruth C; Campa, Daniele; Berndt, Sonja I; Lindstrom, Sara; Kraft, Peter; Schumacher, Fredrick R; Siddiq, Afshan; Papatheodorou, Stefania I; Stanford, Janet L; Albanes, Demetrius; Virtamo, Jarmo; Weinstein, Stephanie J; Diver, W Ryan; Gapstur, Susan M; Stevens, Victoria L; Boeing, Heiner; Bueno-de-Mesquita, H Bas; Barricarte Gurrea, Aurelio; Kaaks, Rudolf; Khaw, Kay-Tee; Krogh, Vittorio; Overvad, Kim; Riboli, Elio; Trichopoulos, Dimitrios; Giovannucci, Edward; Stampfer, Meir; Haiman, Christopher; Henderson, Brian; Le Marchand, Loic; Gaziano, J Michael; Hunter, David J; Koutros, Stella; Yeager, Meredith; Hoover, Robert N; Chanock, Stephen J; Wacholder, Sholom; Key, Timothy J; Tsilidis, Konstantinos K

2015-04-01

No single-nucleotide polymorphisms (SNPs) specific for aggressive prostate cancer have been identified in genome-wide association studies (GWAS). To test if SNPs associated with other traits may also affect the risk of aggressive prostate cancer. SNPs implicated in any phenotype other than prostate cancer (p≤10(-7)) were identified through the catalog of published GWAS and tested in 2891 aggressive prostate cancer cases and 4592 controls from the Breast and Prostate Cancer Cohort Consortium (BPC3). The 40 most significant SNPs were followed up in 4872 aggressive prostate cancer cases and 24,534 controls from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. Odds ratios (ORs) and 95% confidence intervals (CIs) for aggressive prostate cancer were estimated. A total of 4666 SNPs were evaluated by the BPC3. Two signals were seen in regions already reported for prostate cancer risk. rs7014346 at 8q24.21 was marginally associated with aggressive prostate cancer in the BPC3 trial (p=1.6×10(-6)), whereas after meta-analysis by PRACTICAL the summary OR was 1.21 (95% CI 1.16-1.27; p=3.22×10(-18)). rs9900242 at 17q24.3 was also marginally associated with aggressive disease in the meta-analysis (OR 0.90, 95% CI 0.86-0.94; p=2.5×10(-6)). Neither of these SNPs remained statistically significant when conditioning on correlated known prostate cancer SNPs. The meta-analysis by BPC3 and PRACTICAL identified a third promising signal, marked by rs16844874 at 2q34, independent of known prostate cancer loci (OR 1.12, 95% CI 1.06-1.19; p=4.67×10(-5)); it has been shown that SNPs correlated with this signal affect glycine concentrations. The main limitation is the heterogeneity in the definition of aggressive prostate cancer between BPC3 and PRACTICAL. We did not identify new SNPs for aggressive prostate cancer. However, rs16844874 may provide preliminary genetic evidence on the role of the glycine pathway in prostate cancer etiology. We evaluated whether genetic variants associated with several traits are linked to the risk of aggressive prostate cancer. No new such variants were identified. Copyright © 2014 European Association of Urology. All rights reserved.

Is it necessary to cure prostate cancer when it is possible? (Understanding the role of prostate inflammation resolution to prostate cancer evolution)

PubMed Central

Wheeler, Ronald E

2007-01-01

Objective: Definitive therapy with radical prostatectomy, cryotherapy, or radiation therapy generally follows the initial diagnosis of prostate cancer, particularly when men have at least 10 additional years of life expectancy. There is growing concern regarding the optimal conservative treatment for patients who decline or do not otherwise qualify for such definitive curative treatment. For those patients who choose a watchful waiting approach, it would be beneficial to know what specific dietary and nutritional methods could potentially slow the progression of their disease. In this prospective study, it was our goal to analyze the efficacy and safety of treating prostate cancer conservatively using the principles of a Mediterranean diet in association with a specific prostate nutritional supplement. Method: Twenty-three men aged 43–74 (median age: 64) with biopsy proven, organ-confined prostate cancer who had already declined immediate hormonal therapy and attempts at a curative cancer treatment agreed to participate in a Chronic Disease Management (CDM) protocol highlighted by diet with a specific prostate nutritional supplement. The diet recommended was a modified Mediterranean diet while a patented nutritional prostatitis formula (Peenuts®) was the supplement common to all patients. Prostate specific antigen (PSA), a recognized marker of prostate disease and prostate cancer activity, was the primary indicator to validate exacerbation or suppression of disease. All men were followed with serial PSA testing, a digital rectal exam, an International Prostate Symptom Score index (IPSS-Index) and an expressed prostatic secretion (EPS) examination. The primary Gleason sum/score represented in this study was 6 (n = 11), while Gleason sum patterns 5, 5/6, 6/7, and 7 were also evaluated. Referencing the Partin Tables, organ confinement was predicted to be 66%. Results: Eighty-seven percent of men (n = 20) noted a 58% reduction (range of improvement: 13%–90%) in PSA over an average of 38.5 months (range: 13–84 months). The remaining 13% of men included three men who experienced a mild elevation in PSA of 0.3 ng/ml, 0.7 ng/ml, and 0.9 ng/ml over 14 months, 42 months, and 34 months, respectively. Fifteen men had completed an initial and secondary IPSS-Index while 14 men had undergone an initial and secondary EPS. The mean percentage reduction in IPSS-Index was 61% (range: 20%–100% with a median of 55%), while men evaluated with EPS examinations noted a mean percentage reduction in white blood cells of 77.5% (range: 33%–99% with a median of 82%). These results were evaluated using the t-test, Wilcoxon Analysis and the Null Hypothesis and found to be statistically significant. Conclusion: Clearly there is a need to develop effective alternative conservative therapies for the increasing numbers of prostate cancer patients who will not tolerate definitive curative measures or simply choose a conservative approach. Although this prospective study had no control arm, was of limited duration and included only 23 participants, it did appear to show significant benefit to the majority of prostate cancer patients treated with selective nutritional and dietary therapy alone. Such treatments may provide a safe and effective long-term treatment alternative for some patients. Further study is encouraged. PMID:18044088

Combination of Autoantibody Signature with PSA Level Enables a Highly Accurate Blood-Based Differentiation of Prostate Cancer Patients from Patients with Benign Prostatic Hyperplasia.

PubMed

Leidinger, Petra; Keller, Andreas; Milchram, Lisa; Harz, Christian; Hart, Martin; Werth, Angelika; Lenhof, Hans-Peter; Weinhäusel, Andreas; Keck, Bastian; Wullich, Bernd; Ludwig, Nicole; Meese, Eckart

2015-01-01

Although an increased level of the prostate-specific antigen can be an indication for prostate cancer, other reasons often lead to a high rate of false positive results. Therefore, an additional serological screening of autoantibodies in patients' sera could improve the detection of prostate cancer. We performed protein macroarray screening with sera from 49 prostate cancer patients, 70 patients with benign prostatic hyperplasia and 28 healthy controls and compared the autoimmune response in those groups. We were able to distinguish prostate cancer patients from normal controls with an accuracy of 83.2%, patients with benign prostatic hyperplasia from normal controls with an accuracy of 86.0% and prostate cancer patients from patients with benign prostatic hyperplasia with an accuracy of 70.3%. Combining seroreactivity pattern with a PSA level of higher than 4.0 ng/ml this classification could be improved to an accuracy of 84.1%. For selected proteins we were able to confirm the differential expression by using luminex on 84 samples. We provide a minimally invasive serological method to reduce false positive results in detection of prostate cancer and according to PSA screening to distinguish men with prostate cancer from men with benign prostatic hyperplasia.

Treating Localized Prostate Cancer

MedlinePlus

... Prostate Cancer: Update of a 2008 Systematic Review . Comparative Effectiveness Review No. 146. (Prepared by the ECRI ... Prostate Cancer Research Protocol Archived March 29, 2013 Comparative Effectiveness of Therapies for Clinically Localized Prostate Cancer: ...

Night work and prostate cancer in men: a Swedish prospective cohort study

PubMed Central

Åkerstedt, Torbjrn; Narusyte, Jurgita; Svedberg, Pia; Kecklund, Göran; Alexanderson, Kristina

2017-01-01

Objectives Prostate cancer is the most common cancer and the second leading cause of cancer-related deaths among men, but the contributing factors are unclear. One such may be night work because of the day/night alternation of work and the resulting disturbance of the circadian system. The purpose of the present study was to investigate the prospective relation between number of years with night work and prostate cancer in men. Design Cohort study comparing night and day working twins with respect to incident prostate cancer in 12 322 men. Setting Individuals in the Swedish Twin Registry. Participants 12 322 male twins. Outcome measures Prostate cancer diagnoses obtained from the Swedish Cancer Registry with a follow-up time of 12 years, with a total number of cases=454. Results Multiple Cox proportional hazard regression analysis, adjusted for a number of covariates, showed no association between ever night work and prostate cancer, nor for duration of night work and prostate cancer. Analysis of twin pairs discordant for prostate cancer (n=332) showed no significant association between night work and prostate cancer. Conclusions The results, together with previous studies, suggest that night work does not seem to constitute a risk factor for prostate cancer. PMID:28600375

Antibody Responses to Prostate-Associated Antigens in Patients with Prostatitis and Prostate Cancer

PubMed Central

Maricque, Brett B.; Eickhoff, Jens C.; McNeel, Douglas G.

2010-01-01

Background An important focus of tumor immunotherapy has been the identification of appropriate antigenic targets. Serum-based screening approaches have led to the discovery of hundreds of tumor-associated antigens recognized by IgG. Our efforts to identify immunologically recognized proteins in prostate cancer have yielded a multitude of antigens, however prioritizing these antigens as targets for evaluation in immunotherapies has been challenging. In this report, we set out to determine whether the evaluation of multiple antigenic targets would allow the identification of a subset of antigens that are common immunologic targets in patients with prostate cancer. Methods Using a phage immunoblot approach, we evaluated IgG responses in patients with prostate cancer (n=126), patients with chronic prostatitis (n=45), and men without prostate disease (n=53). Results We found that patients with prostate cancer or prostatitis have IgG specific for multiple common antigens. A subset of 23 proteins was identified to which IgG were detected in 38% of patients with prostate cancer and 33% patients with prostatitis versus 6% of controls (p<0.001 and p=0.003, respectively). Responses to multiple members were not higher in patients with advanced disease, suggesting antibody immune responses occur early in the natural history of cancer progression. Conclusions These findings suggest an association between inflammatory conditions of the prostate and prostate cancer, and suggest that IgG responses to a panel of commonly recognized prostate antigens could be potentially used in the identification of patients at risk for prostate cancer or as a tool to identify immune responses elicited to prostate tissue. PMID:20632317

Evaluation of a novel label-free photonic-crystal biosensor imaging system for the detection of prostate cancer cells

NASA Astrophysics Data System (ADS)

DeLuna, Frank; Ding, XiaoFie; Sun, Lu-Zhe; Ye, Jing Yong

2017-02-01

Biomarker screening for prostate-specific antigen (PSA) is the current clinical standard for detection of prostate cancer. However this method has shown many limitations, mainly in its specificity, which can lead to a high false positive rate. Thus, there is a growing need in developing a more specific detection system for prostate cancer. Using a Photonic- Crystal-based biosensor in a Total-Internal-Reflection (PC-TIR) configuration, we demonstrate the use of refractive index (RI) to accomplish label-free detection of prostate cancer cells against non-cancerous prostate epithelial cells. The PC-TIR biosensor possesses an open microcavity, which in contrast to traditional closed microcavities, allows for easier access of analyte molecules or cells to interact with its sensing surface. In this study, an imaging system was designed using the PC-TIR biosensor to quantify cell RI as the contrast parameter for prostate cancer detection. Non-cancerous BPH-1 prostate epithelial cells and prostate cancer PC-3 cells were placed on a single biosensor and measured concurrently. Recorded image data was then analyzed through a home-built MatLab program. Results demonstrate that RI is a suitable variable for differentiation between prostate cancer cells and non-cancerous prostate epithelial cells. Our study shows clinical potential in utilizing RI test for the detection of prostate cancer.

Deregulation of E-cadherin, β-catenin, APC and Caveolin-1 expression occurs in canine prostate cancer and metastatic processes.

PubMed

Kobayashi, Priscila E; Fonseca-Alves, Carlos E; Rivera-Calderón, Luis G; Carvalho, Márcio; Kuasne, Hellen; Rogatto, Silvia R; Laufer-Amorim, Renée

2018-06-01

Prostate cancer is a heterogeneous disease with high levels of clinical and gene heterogeneity, consequently offering several targets for therapy. Dogs with naturally occurring prostate cancer are useful models for molecular investigations and studying new treatment efficacy. Three genes and proteins associated with the WNT pathway (β-catenin, APC and E-cadherin) and Caveolin-1 (CAV-1) were evaluated in canine pre-neoplastic proliferative inflammatory atrophy (PIA), prostate cancer and metastatic disease. The APC gene methylation status was also investigated. As in human prostate cancer, cytoplasmic and nuclear β-catenin, which are fundamental for activating the canonical WNT pathway, were found in canine prostate cancer and metastasis. Membranous E-cadherin was also lost in these lesions, allowing cellular migration to the stroma and nuclear localization of β-catenin. In contrast to human prostate tumours, no APC downregulation or hypermethylation was found in canine prostate cancer. The CAV-1 gene and protein overexpression were found in canine prostate cancer, and as in humans, the highest levels were found in Gleason scores ≥8. In conclusion, as with human prostate cancer, β-catenin and E-cadherin in the WNT pathway, as well as Caveolin-1, are molecular drivers in canine prostate cancer. These findings provide additional evidence that dogs are useful models for studying new therapeutic targets in prostate cancer. Copyright © 2018 Elsevier Ltd. All rights reserved.

Prostate-Specific G-Protein Coupled Receptor, an Emerging Biomarker Regulating Inflammation and Prostate Cancer Invasion.

PubMed

Rodriguez, M; Siwko, S; Liu, M

2016-01-01

Prostate cancer is highly prevalent among men in developed countries, but a significant proportion of detected cancers remain indolent, never progressing into aggressive carcinomas. This highlights the need to develop refined biomarkers that can distinguish between indolent and potentially dangerous cases. The prostate-specific G-protein coupled receptor (PSGR, or OR51E2) is an olfactory receptor family member with highly specific expression in human prostate epithelium that is highly overexpressed in PIN and prostate cancer. PSGR has been functionally implicated in prostate cancer cell invasiveness, suggesting a potential role in the transition to metastatic PCa. Recently, transgenic mice overexpressing PSGR in the prostate were reported to develop an acute inflammatory response followed by emergence of low grade PIN, whereas mice with compound PSGR overexpression and loss of PTEN exhibited accelerated formation of invasive prostate adenocarcinoma. This article will review recent PSGR findings with a focus on its role as a potential prostate cancer biomarker and regulator of prostate cancer invasion and inflammation.

78 FR 54745 - National Prostate Cancer Awareness Month, 2013

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-06

... National Prostate Cancer Awareness Month, 2013 By the President of the United States of America A Proclamation Among American men, prostate cancer is both the second most commonly diagnosed cancer and the second-leading cause of cancer deaths. Although prostate cancer incidence and mortality rates have...

Androgen receptor mediated epigenetic regulation of CRISP3 promoter in prostate cancer cells.

PubMed

Pathak, Bhakti R; Breed, Ananya A; Deshmukh, Priyanka; Mahale, Smita D

2018-07-01

Cysteine-rich secretory protein 3 (CRISP3) is one of the most upregulated genes in prostate cancer. Androgen receptor (AR) plays an important role not only in initial stages of prostate cancer development but also in the advanced stage of castration-resistant prostate cancer (CRPC). Role of AR in regulation of CRISP3 expression is not yet known. In order to understand the regulation of CRISP3 expression, various overlapping fragments of CRISP3 promoter were cloned in pGL3 luciferase reporter vector. All constructs were transiently and stably transfected in PC3 (CRISP3 negative) and LNCaP (CRISP3 positive) cell lines and promoter activity was measured by luciferase assay. Promoter activity of LNCaP stable clones was significantly higher than PC3 stable clones. Further in CRISP3 negative PC3 and RWPE-1 cells, CRISP3 promoter was shown to be silenced by histone deacetylation. Treatment of LNCaP cells with DHT resulted in increase in levels of CRISP3 transcript and protein. AR dependency of CRISP3 promoter was also evaluated in LNCaP stable clones by luciferase assay. To provide molecular evidence of epigenetic regulation of CRISP3 promoter and its response to DHT, ChIP PCR was performed in PC3 and LNCaP cells. Our results demonstrate that CRISP3 expression in prostate cancer cells is androgen dependent and in AR positive cells, CRISP3 promoter is epigenetically regulated by AR. Copyright © 2018 Elsevier Ltd. All rights reserved.

GTI-2040 and Docetaxel in Treating Patients With Recurrent, Metastatic, or Unresectable Locally Advanced Non-Small Cell Lung Cancer, Prostate Cancer, or Other Solid Tumors

ClinicalTrials.gov

2013-01-23

Recurrent Non-small Cell Lung Cancer; Recurrent Prostate Cancer; Stage III Prostate Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Prostate Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Understanding how prostate cancer patients value the current treatment options for metastatic castration resistant prostate cancer.

PubMed

Benidir, Tarik; Hersey, Karen; Finelli, Antonio; Hamilton, Rob; Joshua, Anthony M; Kulkarni, Girish; Zlotta, Alexandre; Fleshner, Neil

2018-05-01

Several new compounds are now available for castration resistant prostate cancer (CRPC). Individual costs range between $40,000 and $93,000 with mean survival extensions from 2.4 to 4.8 months. Currently, it remains unclear how patients with prostate cancer (PCa) value the effect of these therapies in the setting of CRPC. To assess patient understanding of core cancer concepts, opinions on the cost and overall benefit of CRPC drugs, whether out-of-pocket costs would change opinions and whether patients would ultimately opt out of CRPC drug treatment for an end-of-life (EOL) premium. We conducted a qualitative survey among patients with various PCa states ranging from active surveillance to CRPC and from various familial, financial and educational demographics. Through a series of hypothetical scenarios, we extrapolated opinions on CRPC drug value, efficacy and monetary worth. We assessed patient willingness to accept an EOL ($50,000) premium in lieu of CRPC drug treatment. Statistically, chi-squared analysis and Fisher's exact test were used when appropriate. In total, 103 patients completed the questionnaire, one-half of whom did not understand "advanced PCa" state and more than one-third of the concept of palliative care despite multiple meetings with Urologists. Patients willingness-to-pay and proposed drug value was higher than that accepted by government when government funded, with costs exceeding $250,000 per person, but lower than that accepted by government when self-funded. A majority (60%) would accept/consider the EOL premium in the setting of CRPC. Patients with higher education were more skeptical about CRPC drug value and more likely to accept the EOL premium (P = 0.003.) CONCLUSION: Patients have an incomplete understanding of their own disease prognosis and its therapeutic options. This ultimately influences patient decision-making. Education, income and out-of-pocket costs diminished opinion of CRPC drugs considerably. As such, an EOL premium should be considered in subsets of patients. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

Minimally important difference for the Expanded Prostate Cancer Index Composite Short Form.

PubMed

Skolarus, Ted A; Dunn, Rodney L; Sanda, Martin G; Chang, Peter; Greenfield, Thomas K; Litwin, Mark S; Wei, John T

2015-01-01

To establish a score threshold that constitutes a clinically relevant change for each domain of the Expanded Prostate Cancer Index Composite (EPIC) Short Form (EPIC-26). Although its use in clinical practice and clinical trials has increased worldwide, the clinical interpretation of this 26-item disease-specific patient-reported quality of life questionnaire for men with localized prostate cancer would be facilitated by characterization of score thresholds for clinically relevant change (the minimally important differences [MIDs]). We used distribution- and anchor-based approaches to establish the MID range for each EPIC-26 domain (urinary, sexual, bowel, and vitality/hormonal) based on a prospective multi-institutional cohort of 1201 men treated for prostate cancer between 2003 and 2006 and followed up for 3 years after treatment. For the anchor-based approach, we compared within-subject and between-subject score changes for each domain to an external "anchor" measure of overall cancer treatment satisfaction. We found the bowel and vitality/hormonal domains to have the lowest MID range (a 4-6 point change should be considered clinically relevant), whereas the sexual domain had the greatest MID values (10-12). Urinary incontinence appeared to have a greater MID range (6-9) than the urinary irritation/obstruction domain (5-7). Using 2 independent approaches, we established the MIDs for each EPIC-26 domain. A definition of these MID values is essential for the researcher or clinician to understand when changes in symptom burden among prostate cancer survivors are clinically relevant. Copyright © 2015 Elsevier Inc. All rights reserved.

Understanding and Targeting Tumor Microenvironment in Prostate Cancer to Inhibit Tumor Progression and Castration Resistance

DTIC Science & Technology

2016-10-01

report 3 . DATES COVERED 30Sep2015 - 29Sep2016 4. TITLE AND SUBTITLE Understanding and Targeting Tumor Microenvironment in Prostate 5a. CONTRACT...Contents Page 1. Introduction………………………………………………………….4 2. Keywords…………………………………………………………….4 3 . Accomplishments………..…………………………………………...5 4. Impact...Organizations……………14 8. Special Reporting Requirements……………………………………14 9. Appendices……………………………………………………………15 Page 3 of 14 1. INTRODUCTION Prostate cancer

Increased cancer cell proliferation in prostate cancer patients with high levels of serum folate

USDA-ARS?s Scientific Manuscript database

Introduction: A recent clinical trial revealed that folic acid supplementation is associated with an increased incidence of prostate cancer (1). The present study evaluates serum and prostate tissue folate levels in men with prostate cancer, compared to histologically normal prostate glands from can...

Extended Cancer Education for Longer-Term Survivors in Primary Care for Patients With Stage I-II Breast or Prostate Cancer or Stage I-III Colorectal Cancer

ClinicalTrials.gov

2017-11-15

Stage I Breast Cancer; Stage I Colorectal Cancer AJCC v6 and v7; Stage I Prostate Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage II Colorectal Cancer AJCC v7; Stage II Prostate Cancer; Stage IIA Breast Cancer; Stage IIA Colorectal Cancer AJCC v7; Stage IIA Prostate Cancer; Stage IIB Breast Cancer; Stage IIB Colorectal Cancer AJCC v7; Stage IIB Prostate Cancer; Stage IIC Colorectal Cancer AJCC v7; Stage III Colorectal Cancer AJCC v7; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7

The influence of PSA-RNA yield on the analysis of expressed prostatic secretions (EPS) for prostate cancer diagnosis.

PubMed

Whelan, Christopher; Crocitto, Laura; Kawachi, Mark; Chan, Kevin; Smith, David; Wilson, Timothy; Smith, Steven

2013-02-01

In patients with prostate cancer, luminal prostate-specific antigen (PSA) enters the circulation because the basement membrane and glandular epithelium are damaged. Given that excess mobilization of prostate cells during prostatic massage can influence normalization in diagnostic testing, we studied PSA mRNA levels in expressed prostatic secretions (EPS) from patients undergoing biopsy for prostate cancer to determine if prostate cells are preferentially mobilized from patients with prostate cancer during prostatic massage. Quantitative Reverse-Transcription PCR (qRT-PCR) was used to measure the RNA levels of GAPDH, PSA, TMPRSS2:ERG and PCA3 in EPS specimens obtained from patients undergoing biopsy for prostate cancer. The level of PSA mRNA is significantly elevated in EPS specimens obtained from patients with a subsequent diagnosis of prostate cancer. This correlation influenced diagnostic testing results from EPS in two ways. First, when used as an exclusion parameter it appears to improve the diagnostic performance of TMPRSS2:ERG in EPS. Second, when used as a normalization parameter it appears to decrease the performance of these same tests. When comparing the results of mRNA based prostate cancer diagnostics in EPS it will be essential to consider PSA mRNA as a prostate specific gene and not a housekeeping gene.

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.

Prostate specific antigen velocity does not aid prostate cancer detection in men with prior negative biopsy.

PubMed

Vickers, Andrew J; Wolters, Tineke; Savage, Caroline J; Cronin, Angel M; O'Brien, M Frank; Roobol, Monique J; Aus, Gunnar; Scardino, Peter T; Hugosson, Jonas; Schröder, Fritz H; Lilja, Hans

2010-09-01

Prostate specific antigen velocity has been proposed as a marker to aid in prostate cancer detection. We determined whether prostate specific antigen velocity could predict repeat biopsy results in men with persistently increased prostate specific antigen after initial negative biopsy. We identified 1,837 men who participated in the Göteborg or Rotterdam section of the European Randomized Screening study of Prostate Cancer and who underwent 1 or more subsequent prostate biopsies after an initial negative finding. We evaluated whether prostate specific antigen velocity improved predictive accuracy beyond that of prostate specific antigen alone. Of the 2,579 repeat biopsies 363 (14%) were positive for prostate cancer, of which 44 (1.7%) were high grade (Gleason score 7 or greater). Prostate specific antigen velocity was statistically associated with cancer risk but had low predictive accuracy (AUC 0.55, p <0.001). There was some evidence that prostate specific antigen velocity improved AUC compared to prostate specific antigen for high grade cancer. However, the small increase in risk associated with high prostate specific antigen velocity (from 1.7% to 2.8% as velocity increased from 0 to 1 ng/ml per year) had questionable clinical relevance. Men with prior negative biopsy are at lower risk for prostate cancer at subsequent biopsies with high grade disease particularly rare. We found little evidence to support prostate specific antigen velocity to aid in decisions about repeat biopsy for prostate cancer. 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Keratin 13 expression reprograms bone and brain metastases of human prostate cancer cells.

PubMed

Li, Qinlong; Yin, Lijuan; Jones, Lawrence W; Chu, Gina C-Y; Wu, Jason B-Y; Huang, Jen-Ming; Li, Quanlin; You, Sungyong; Kim, Jayoung; Lu, Yi-Tsung; Mrdenovic, Stefan; Wang, Ruoxiang; Freeman, Michael R; Garraway, Isla; Lewis, Michael S; Chung, Leland W K; Zhau, Haiyen E

2016-12-20

Lethal progression of prostate cancer metastasis can be improved by developing animal models that recapitulate the clinical conditions. We report here that cytokeratin 13 (KRT13), an intermediate filament protein, plays a directive role in prostate cancer bone, brain, and soft tissue metastases. KRT13 expression was elevated in bone, brain, and soft tissue metastatic prostate cancer cell lines and in primary and metastatic clinical prostate, lung, and breast cancer specimens. When KRT13 expression was determined at a single cell level in primary tumor tissues of 44 prostate cancer cases, KRT13 level predicted bone metastasis and the overall survival of prostate cancer patients. Genetically enforced KRT13 expression in human prostate cancer cell lines drove metastases toward mouse bone, brain and soft tissues through a RANKL-independent mechanism, as KRT13 altered the expression of genes associated with EMT, stemness, neuroendocrine/neuromimicry, osteomimicry, development, and extracellular matrices, but not receptor activator NF-κB ligand (RANKL) signaling networks in prostate cancer cells. Our results suggest new inhibitors targeting RANKL-independent pathways should be developed for the treatment of prostate cancer bone and soft tissue metastases.

Antiproliferative activity of novel imidazopyridine derivatives on castration-resistant human prostate cancer cells.

PubMed

Muniyan, Sakthivel; Chou, Yu-Wei; Ingersoll, Matthew A; Devine, Alexus; Morris, Marisha; Odero-Marah, Valerie A; Khan, Shafiq A; Chaney, William G; Bu, Xiu R; Lin, Ming-Fong

2014-10-10

Metastatic prostate cancer (mPCa) relapses after a short period of androgen deprivation therapy and becomes the castration-resistant prostate cancer (CR PCa); to which the treatment is limited. Hence, it is imperative to identify novel therapeutic agents towards this patient population. In the present study, antiproliferative activities of novel imidazopyridines were compared. Among three derivatives, PHE, AMD and AMN, examined, AMD showed the highest inhibitory activity on LNCaP C-81 cell proliferation, following dose- and time-dependent manner. Additionally, AMD exhibited significant antiproliferative effect against a panel of PCa cells, but not normal prostate epithelial cells. Further, when compared to AMD, its derivative DME showed higher inhibitory activities on PCa cell proliferation, clonogenic potential and in vitro tumorigenicity. The inhibitory activity was apparently in part due to the induction of apoptosis. Mechanistic studies indicate that AMD and DME treatments inhibited both AR and PI3K/Akt signaling. The results suggest that better understanding of inhibitory mechanisms of AMD and DME could help design novel therapeutic agents for improving the treatment of CR PCa. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Antiproliferative activity of novel imidazopyridine derivatives on castration-resistant human prostate cancer cells

PubMed Central

Muniyan, Sakthivel; Chou, Yu-Wei; Ingersoll, Matthew A.; Devine, Alexus; Morris, Marisha; Odero-Marah, Valerie A.; Khan, Shafiq A.; Chaney, William G.; Bu, Xiu R.; Lin, Ming-Fong

2014-01-01

Metastatic prostate cancer (mPCa) relapses after a short period of androgen deprivation therapy and becomes the castration-resistant prostate cancer (CR PCa); to which the treatment is limited. Hence, it is imperative to identify novel therapeutic agents towards this patient population. In the present study, antiproliferative activities of novel imidazopyridines were compared. Among three derivatives, PHE, AMD and AMN, examined, AMD showed the highest inhibitory activity on LNCaP C-81 cell proliferation, following dose- and time-dependent manner. Additionally, AMD exhibited significant antiproliferative effect against a panel of PCa cells, but not normal prostate epithelial cells. Further, when compared to AMD, its derivative DME showed higher inhibitory activities on PCa cell proliferation, clonogenic potential and in vitro tumorigenicity. The inhibitory activity was apparently in part due to the induction of apoptosis. Mechanistic studies indicate that AMD and DME treatments inhibited both AR and PI3K/Akt signaling. The results suggest that better understanding of inhibitory mechanisms of AMD and DME could help design novel therapeutic agents for improving the treatment of CR PCa. PMID:25050738

Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation.

PubMed

Gusev, Alexander; Shi, Huwenbo; Kichaev, Gleb; Pomerantz, Mark; Li, Fugen; Long, Henry W; Ingles, Sue A; Kittles, Rick A; Strom, Sara S; Rybicki, Benjamin A; Nemesure, Barbara; Isaacs, William B; Zheng, Wei; Pettaway, Curtis A; Yeboah, Edward D; Tettey, Yao; Biritwum, Richard B; Adjei, Andrew A; Tay, Evelyn; Truelove, Ann; Niwa, Shelley; Chokkalingam, Anand P; John, Esther M; Murphy, Adam B; Signorello, Lisa B; Carpten, John; Leske, M Cristina; Wu, Suh-Yuh; Hennis, Anslem J M; Neslund-Dudas, Christine; Hsing, Ann W; Chu, Lisa; Goodman, Phyllis J; Klein, Eric A; Witte, John S; Casey, Graham; Kaggwa, Sam; Cook, Michael B; Stram, Daniel O; Blot, William J; Eeles, Rosalind A; Easton, Douglas; Kote-Jarai, Zsofia; Al Olama, Ali Amin; Benlloch, Sara; Muir, Kenneth; Giles, Graham G; Southey, Melissa C; Fitzgerald, Liesel M; Gronberg, Henrik; Wiklund, Fredrik; Aly, Markus; Henderson, Brian E; 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; Wokolorczyk, Dominika; Kluzniak, Wojciech; Cannon-Albright, Lisa; Teerlink, Craig; Brenner, Hermann; Dieffenbach, Aida K; Arndt, Volker; Park, Jong Y; Sellers, Thomas A; Lin, Hui-Yi; Slavov, Chavdar; Kaneva, Radka; Mitev, Vanio; Batra, Jyotsna; Spurdle, Amanda; Clements, Judith A; Teixeira, Manuel R; Pandha, Hardev; Michael, Agnieszka; Paulo, Paula; Maia, Sofia; Kierzek, Andrzej; Conti, David V; Albanes, Demetrius; Berg, Christine; Berndt, Sonja I; Campa, Daniele; Crawford, E David; Diver, W Ryan; Gapstur, Susan M; Gaziano, J Michael; Giovannucci, Edward; Hoover, Robert; Hunter, David J; Johansson, Mattias; Kraft, Peter; Le Marchand, Loic; Lindström, Sara; Navarro, Carmen; Overvad, Kim; Riboli, Elio; Siddiq, Afshan; Stevens, Victoria L; Trichopoulos, Dimitrios; Vineis, Paolo; Yeager, Meredith; Trynka, Gosia; Raychaudhuri, Soumya; Schumacher, Frederick R; Price, Alkes L; Freedman, Matthew L; Haiman, Christopher A; Pasaniuc, Bogdan

2016-04-07

Although genome-wide association studies have identified over 100 risk loci that explain ∼33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic architecture from common variation underlying PrCa risk. Our findings showcase the power of integrating functional annotation with genetic data to understand the genetic basis of PrCa.

Stress alters the expression of cancer-related genes in the prostate.

PubMed

Flores, Ivan E; Sierra-Fonseca, Jorge A; Davalos, Olinamyr; Saenz, Luis A; Castellanos, Maria M; Zavala, Jaidee K; Gosselink, Kristin L

2017-09-05

Prostate cancer is a major contributor to mortality worldwide, and significant efforts are being undertaken to decipher specific cellular and molecular pathways underlying the disease. Chronic stress is known to suppress reproductive function and promote tumor progression in several cancer models, but our understanding of the mechanisms through which stress contributes to cancer development and progression is incomplete. We therefore examined the relationship between stress, modulation of the gonadotropin-releasing hormone (GnRH) system, and changes in the expression of cancer-related genes in the rat prostate. Adult male rats were acutely or repeatedly exposed to restraint stress, and compared to unstressed controls and groups that were allowed 14 days of recovery from the stress. Prostate tissue was collected and frozen for gene expression analyses by PCR array before the rats were transcardially perfused; and brain tissues harvested and immunohistochemically stained for Fos to determine neuronal activation. Acute stress elevated Fos expression in the paraventricular nucleus of the hypothalamus (PVH), an effect that habituated with repeated stress exposure. Data from the PCR arrays showed that repeated stress significantly increases the transcript levels of several genes associated with cellular proliferation, including proto-oncogenes. Data from another array platform showed that both acute and repeated stress can induce significant changes in metastatic gene expression. The functional diversity of genes with altered expression, which includes transcription factors, growth factor receptors, apoptotic genes, and extracellular matrix components, suggests that stress is able to induce aberrant changes in pathways that are deregulated in prostate cancer. Our findings further support the notion that stress can affect cancer outcomes, perhaps by interfering with neuroendocrine mechanisms involved in the control of reproduction.

Current state of prostate cancer treatment in Jamaica.

PubMed

Morrison, Belinda F; Aiken, William D; Mayhew, Richard

2014-01-01

Prostate cancer is the commonest cancer in Jamaica as well as the leading cause of cancer-related deaths. One report suggested that Jamaica has the highest incidence rate of prostate cancer in the world, with an age-standardised rate of 304/100,000 per year. The Caribbean region is reported to have the highest mortality rate of prostate cancer worldwide. Prostate cancer accounts for a large portion of the clinical practice for health-care practitioners in Jamaica. The Jamaica Urological Society is a professional body comprising 19 urologists in Jamaica who provide most of the care for men with prostate cancer in collaboration with medical oncologists, radiation oncologists, and a palliative care physician. The health-care system is structured in two tiers in Jamaica: public and private. The urologist-to-patient ratio is high, and this limits adequate urological care. Screening for prostate cancer is not a national policy in Jamaica. However, the Jamaica Urological Society and the Jamaica Cancer Society work synergistically to promote screening as well as to provide patient education for prostate cancer. Adequate treatment for localised prostate cancer is available in Jamaica in the forms of active surveillance, nerve-sparing radical retropubic prostatectomy, external beam radiation, and brachytherapy. However, there is a geographic maldistribution of centres that provide prostate cancer treatment, which leads to treatment delays. Also, there is difficulty in affording some treatment options in the private health-care sectors. Androgen deprivation therapy is available for treatment of locally advanced and metastatic prostate cancer and is subsidised through a programme called the National Health Fund. Second-line hormonal agents and chemotherapeutic agents are available but are costly to most of the population. The infrastructure for treatment of prostate cancer in Jamaica is good, but it requires additional technological advances as well as additional specialist services.

Finasteride Concentrations and Prostate Cancer Risk: Results from the Prostate Cancer Prevention Trial

PubMed Central

Till, Cathee; Goodman, Phyllis J.; Chen, Xiaohong; Leach, Robin J.; Johnson-Pais, Teresa L.; Hsing, Ann W.; Hoque, Ashraful; Tangen, Catherine M.; Chu, Lisa; Parnes, Howard L.; Schenk, Jeannette M.; Reichardt, Juergen K. V.; Thompson, Ian M.; Figg, William D.

2015-01-01

Objective In the Prostate Cancer Prevention Trial (PCPT), finasteride reduced the risk of prostate cancer by 25%, even though high-grade prostate cancer was more common in the finasteride group. However, it remains to be determined whether finasteride concentrations may affect prostate cancer risk. In this study, we examined the association between serum finasteride concentrations and the risk of prostate cancer in the treatment arm of the PCPT and determined factors involved in modifying drug concentrations. Methods Data for this nested case-control study are from the PCPT. Cases were drawn from men with biopsy-proven prostate cancer and matched controls. Finasteride concentrations were measured using a liquid chromatography-mass spectrometry validated assay. The association of serum finasteride concentrations with prostate cancer risk was determined by logistic regression. We also examine whether polymorphisms in the enzyme target and metabolism genes of finasteride are related to drug concentrations using linear regression. Results and Conclusions Among men with detectable finasteride concentrations, there was no association between finasteride concentrations and prostate cancer risk, low-grade or high-grade, when finasteride concentration was analyzed as a continuous variable or categorized by cutoff points. Since there was no concentration-dependent effect on prostate cancer, any exposure to finasteride intake may reduce prostate cancer risk. Of the twenty-seven SNPs assessed in the enzyme target and metabolism pathway, five SNPs in two genes, CYP3A4 (rs2242480; rs4646437; rs4986910), and CYP3A5 (rs15524; rs776746) were significantly associated with modifying finasteride concentrations. These results suggest that finasteride exposure may reduce prostate cancer risk and finasteride concentrations are affected by genetic variations in genes responsible for altering its metabolism pathway. Trial Registration ClinicalTrials.gov NCT00288106 PMID:25955319

Prostate Cancer Relevant Antigens and Enzymes for Targeted Drug Delivery

PubMed Central

Barve, Ashutosh; Jin, Wei; Cheng, Kun

2014-01-01

Chemotherapy is one of the most widely used approaches in combating advanced prostate cancer, but its therapeutic efficacy is usually insufficient due to lack of specificity and associated toxicity. Lack of targeted delivery to prostate cancer cells is also the primary obstacles in achieving feasible therapeutic effect of other promising agents including peptide, protein, and nucleic acid. Consequently, there remains a critical need for strategies to increase the selectivity of anti-prostate cancer agents. This review will focus on various prostate cancer-specific antigens and enzymes that could be exploited for prostate cancer targeted drug delivery. Among various targeting strategies, active targeting is the most advanced approach to specifically deliver drugs to their designated cancer cells. In this approach, drug carriers are modified with targeting ligands that can specifically bind to prostate cancer-specific antigens. Moreover, there are several specific enzymes in the tumor microenvironment of prostate cancer that can be exploited for stimulus-responsive drug delivery systems. These systems can specifically release the active drug in the tumor microenvironment of prostate cancer, leading to enhanced tumor penetration efficiency. PMID:24878184

Prostate Can Men: The Effect of Body Habitus and Physical Activity

DTIC Science & Technology

2006-02-01

throughout the active phase of the study and 35 men had died of prostate cancer by 1980 . An additional 88 prostate cancer deaths 7 between 1981...prostate cancer by 1980 . An additional 88 prostate cancer deaths between 1981 and 2002 were ascertained using passive follow-up by matching participants...6(4):865- 70. (3) Jain MG, Hislop GT, Howe GR, Ghadirian P. Plant foods, antioxidants, and prostate cancer risk: findings from case-control

Prognostic Significance of Digital Rectal Examination and Prostate Specific Antigen in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Arm.

PubMed

Halpern, Joshua A; Shoag, Jonathan E; Mittal, Sameer; Oromendia, Clara; Ballman, Karla V; Hershman, Dawn L; Wright, Jason D; Shih, Ya-Chen Tina; Nguyen, Paul L; Hu, Jim C

2017-02-01

The absence of definitive data or explicit guidelines regarding the use of digital rectal examination for prostate cancer screening may lead to confusion for physicians and patients alike. We evaluated the prognostic value of abnormal digital rectal examination and prostate specific antigen following the widespread dissemination of prostate specific antigen testing in the U.S. Collectively, men comprising the screening arm of the PLCO cancer screening trial who underwent digital rectal examination screening (35,350) were followed for 314,033 person-years. Adjusted analyses with competing risks regression were performed to assess the association of suspicious (nodularity, induration, asymmetry) digital rectal examination and abnormal prostate specific antigen (4 ng/ml or greater) with the detection of clinically significant prostate cancer, prostate cancer specific mortality and overall mortality. Among all screening encounters with a suspicious digital rectal examination only 15.4% had a concurrently abnormal prostate specific antigen (McNemar's test p <0.001). During followup there were 1,612 clinically significant prostate cancers detected, 64 prostate cancer specific deaths and 4,600 deaths. On multivariable analysis suspicious digital rectal examination and abnormal prostate specific antigen were associated with a greater risk of clinically significant prostate cancer (HR 2.21, 95% CI 1.99-2.44 vs HR 5.48, 95% CI 5.05-5.96, p <0.001 and p <0.001) and prostate cancer specific mortality (HR 2.54, 95% CI 1.41-4.58 vs HR 5.23, 95% CI 3.08-8.88, p=0.002 and p <0.001), respectively. In a secondary analysis of a contemporary U.S. cohort, suspicious digital rectal examination and abnormal prostate specific antigen on routine screening were independently associated with clinically significant prostate cancer and prostate cancer specific mortality. However, additional research is needed to optimize screening protocols. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

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

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

Castration-resistant prostate cancer: targeted therapies.

PubMed

Leo, S; Accettura, C; Lorusso, V

2011-01-01

Castration-resistant prostate cancer (CRPC) refers to patients who no longer respond to surgical or medical castration. Standard treatment options are limited. To review the concepts and rationale behind targeted agents currently in late-stage clinical testing for patients with CRPC. Novel targeted therapies in clinical trials were identified from registries. The Medline database was searched for all relevant reports published from 1996 to October 2009. Bibliographies of the retrieved articles and major international meeting abstracts were hand-searched to identify additional studies. Advances in our understanding of the molecular mechanisms underlying prostate cancer (PCa) progression have translated into a variety of treatment approaches. Agents targeting androgen receptor activation and local steroidogenesis, angiogenesis, immunotherapy, apoptosis, chaperone proteins, the insulin-like growth factor (IGF) pathway, RANK ligand, endothelin receptors, and the Src family kinases are entering or have recently completed accrual to phase III trials for patients with CRPC. There has been an increase in the understanding of the mechanisms of progression of CRPC. A number of new agents targeting mechanisms of PCa progression with early promising results are in clinical trials and have the potential to provide novel treatment options for CRPC in the near future. Copyright © 2011 S. Karger AG, Basel.

Biases in Recommendations for and Acceptance of Prostate Biopsy Significantly Affect Assessment of Prostate Cancer Risk Factors: Results From Two Large Randomized Clinical Trials

PubMed Central

Goodman, Phyllis J.; Till, Cathee; Schenk, Jeannette M.; Lucia, M. Scott; Thompson, Ian M.

2016-01-01

Purpose To identify factors related to who undergoes a prostate biopsy in a screened population and to estimate the impact of biopsy verification on risk factor–prostate cancer associations. Patients and Methods Men who were screened regularly from the placebo arms of two large prostate cancer prevention trials (Prostate Cancer Prevention Trial [PCPT] and Selenium and Vitamin E Cancer Prevention Trial [SELECT]) were examined to define incident prostate cancer cohorts. Because PCPT had an end-of-study biopsy, prostate cancer cases were categorized by a preceding prostate-specific antigen/digital rectal examination prompt (yes/no) and noncases by biopsy-proven negative status (yes v no). We estimated the association of risk factors (age, ethnicity, family history, body mass index, medication use) with prostate cancer and quantified differences in risk associations across cohorts. Results Men 60 to 69 years of age, those with benign prostatic hyperplasia, and those with a family history of prostate cancer were more likely, and those with a higher body mass index (≥ 25), diabetes, or a smoking history were less likely, to undergo biopsy, adjusting for age and longitudinal prostate-specific antigen and digital rectal examination. Medication use, education, and marital status also influenced who underwent biopsy. Some risk factor estimates for prostate cancer varied substantially across cohorts. Black (v other ethnicities) had odds ratios (ORs) that varied from 1.20 for SELECT (community screening standards, epidemiologic-like cohort) to 1.83 for PCPT (end-of-study biopsy supplemented with imputed end points). Statin use in SELECT provided an OR of 0.65 and statin use in in PCPT provided an OR of 0.99, a relative difference of 34%. Conclusion Among screened men enrolled in prostate cancer prevention trials, differences in risk factor estimates for prostate cancer likely underestimate the magnitude of bias found in other cohorts with varying screening and biopsy recommendations and acceptance. Risk factors for prostate cancer derived from epidemiologic studies not only may be erroneous but may lead to misdirected research efforts. PMID:27998216

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

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.

DNA methylation and soy phytoestrogens: quantitative study in DU-145 and PC-3 human prostate cancer cell lines.

PubMed

Adjakly, Mawussi; Bosviel, Rémy; Rabiau, Nadège; Boiteux, Jean-Paul; Bignon, Yves-Jean; Guy, Laurent; Bernard-Gallon, Dominique

2011-12-01

DNA hypermethylation is an epigenetic mechanism which induces silencing of tumor-suppressor genes in prostate cancer. Many studies have reported that specific components of food plants like soy phytoestrogens may have protective effects against prostate carcinogenesis or progression. Genistein and daidzein, the major phytoestrogens, have been reported to have the ability to reverse DNA hypermethylation in cancer cell lines. The aim of this study was to investigate the potential demethylating effects of these two soy compounds on BRCA1, GSTP1, EPHB2 and BRCA2 promoter genes. Prostate cell lines DU-145 and PC-3 were treated with genistein 40 µM, daidzein 110 µM, budesonide (methylating agent) 2 µM and 5-azacytidine (demethylating agent) 2 µM. In these two human prostate cancer cell lines we performed methylation quantification by using Methyl Profiler DNA methylation analysis. This technique is based on a methylation-specific digestion followed by quantitative PCR. We analyzed the corresponding protein expression by western blotting. Soy phytoestrogens induced a demethylation of all promoter regions studied except for BRCA2, which is not methylated in control cell lines. An increase in their protein expression was also demonstrated by western blot analysis and corroborated the potential demethylating effect of soy phytoestrogens. This study showed that the soy phytoestrogens, genistein and daidzein, induce a decrease of methylation of BRCA1, GSTP1 and EPHB2 promoters. Therefore, soy phytoestrogens may have a protective effect on prostate cancer. However, more studies are needed in order to understand the mechanism by which genistein and daidzein have an inhibiting action on DNA methylation.

Incidental prostate cancer at the time of cystectomy: the incidence and clinicopathological features in Chinese patients.

PubMed

Pan, Jiahua; Xue, Wei; Sha, Jianjun; Yang, Hu; Xu, Fan; Xuan, Hanqing; Li, Dong; Huang, Yiran

2014-01-01

To evaluate the incidence and the clinicopathological features of incidental prostate cancer detected in radical cystoprostatectomy (RCP) specimens in Chinese men and to estimate the oncological risk of prostate apex-sparing surgery for such patients. The clinical data and pathological feature of 504 patients who underwent RCP for bladder cancer from January 1999 to March 2013 were retrospectively reviewed. Whole mount serial section of the RCP specimens were cut transversely at 3-4 mm intervals and examined in same pathological institution. Thirty-four out of 504 patients (6.8%) had incidental prostate cancer with a mean age of 70.3 years. 12 cases (35.2%) were diagnosed as significant disease. 4 cases were found to have apex involvement of adenocarcinoma of the prostate while in 5 cases the prostate stroma invasion by urothelial carcinoma were identified (one involved prostate apex). The mean follow-up time was 46.4±33.8 months. Biochemical recurrence occurred in 3 patients but no prostate cancer-related death during the follow-up. There was no statistical significance in cancer specific survival between the clinically significant and insignificant cancer group. The prevalence of incidental prostate cancer in RCP specimens in Chinese patients was remarkably lower than in western people. Most of the incidental prostate cancer was clinically insignificant and patient's prognosis was mainly related to the bladder cancer. Sparing the prostate apex was potentially associated with a 1.0% risk of leaving significant cancer of the prostate or urothelial carcinoma.

Night work and prostate cancer in men: a Swedish prospective cohort study.

PubMed

Åkerstedt, Torbjrn; Narusyte, Jurgita; Svedberg, Pia; Kecklund, Göran; Alexanderson, Kristina

2017-06-08

Prostate cancer is the most common cancer and the second leading cause of cancer-related deaths among men, but the contributing factors are unclear. One such may be night work because of the day/night alternation of work and the resulting disturbance of the circadian system. The purpose of the present study was to investigate the prospective relation between number of years with night work and prostate cancer in men. Cohort study comparing night and day working twins with respect to incident prostate cancer in 12 322 men. Individuals in the Swedish Twin Registry. 12 322 male twins. Prostate cancer diagnoses obtained from the Swedish Cancer Registry with a follow-up time of 12 years, with a total number of cases=454. Multiple Cox proportional hazard regression analysis, adjusted for a number of covariates, showed no association between ever night work and prostate cancer, nor for duration of night work and prostate cancer. Analysis of twin pairs discordant for prostate cancer (n=332) showed no significant association between night work and prostate cancer. The results, together with previous studies, suggest that night work does not seem to constitute a risk factor for prostate cancer. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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.

Elevated phospholipase D activity in androgen-insensitive prostate cancer cells promotes both survival and metastatic phenotypes.

PubMed

Utter, Matthew; Chakraborty, Sohag; Goren, Limor; Feuser, Lucas; Zhu, Yuan-Shan; Foster, David A

2018-06-01

Prostate cells are hormonally driven to grow and divide. Typical treatments for prostate cancer involve blocking activation of the androgen receptor by androgens. Androgen deprivation therapy can lead to the selection of cancer cells that grow and divide independently of androgen receptor activation. Prostate cancer cells that are insensitive to androgens commonly display metastatic phenotypes and reduced long-term survival of patients. In this study we provide evidence that androgen-insensitive prostate cancer cells have elevated PLD activity relative to the androgen-sensitive prostate cancer cells. PLD activity has been linked with promoting survival in many human cancer cell lines; and consistent with the previous studies, suppression of PLD activity in the prostate cancer cells resulted in apoptotic cell death. Of significance, suppressing the elevated PLD activity in androgen resistant prostate cancer lines also blocked the ability of these cells to migrate and invade Matrigel™. Since survival signals are generally an early event in tumorigenesis, the apparent coupling of survival and metastatic phenotypes implies that metastasis is an earlier event in malignant prostate cancer than generally thought. This finding has implications for screening strategies designed to identify prostate cancers before dissemination. Copyright © 2018 Elsevier B.V. All rights reserved.

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.

Evidence of prostate cancer "reverse stage migration" toward more advanced disease at diagnosis: Data from the Pennsylvania Cancer Registry.

PubMed

Reese, Adam C; Wessel, Sean R; Fisher, Susan G; Mydlo, Jack H

2016-08-01

The widespread adoption of prostate-specific antigen-based prostate cancer screening caused a stage migration toward earlier stage disease at diagnosis. We investigated whether this stage migration has persisted in a contemporary analysis of a population-based statewide cancer registry. We analyzed the Pennsylvania Cancer Registry, a statewide registry of all newly diagnosed cancers. Data were collected on prostate cancers diagnosed between 1992 and 2012. We determined age-adjusted prostate cancer incidence and mortality rates, as well as the distribution of tumor stage (localized, regional, or metastatic) at diagnosis, and assessed for changes in these variables over time using joinpoint analysis. Between 1992 and 2012, 210,831 new cases of prostate cancer were diagnosed in Pennsylvania, and 33,948 men died of disease. Age-adjusted prostate cancer incidence rates, and specifically the incidence of localized disease, have decreased dramatically since 2007 to 2008. Due to the decreased diagnosis of localized disease, regional and metastatic tumors have made up a greater percentage of all prostate cancer diagnoses in recent years, despite a relatively stable incidence of these advanced stage tumors. Over the past 2 decades, age-adjusted prostate cancer incidence rates in Pennsylvania have decreased, primarily because of the decreased detection of early-stage disease. There has been a corresponding shift toward more advanced disease at diagnosis. These findings may be explained by the decreased use of prostate-specific antigen-based screening, among other factors. The 2012 United States Preventative Services Task Force recommendations against prostate cancer screening may exacerbate this concerning trend, potentially resulting in an increase in prostate cancer-specific mortality. Copyright © 2016 Elsevier Inc. All rights reserved.

Androgen receptor regulated microRNA miR-182-5p promotes prostate cancer progression by targeting the ARRDC3/ITGB4 pathway

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

Yao, Jingjing; Xu, Chen; Department of Orthopedics, Changzheng Hospital Affiliated to Second Military Medical University, 415th Feng Yang Road, Shanghai, 200003

Abstracts: MicroRNAs (miRNAs) are important endogenous gene regulators that play key roles in prostate cancer development and metastasis. However, specific miRNA expression patterns in prostate cancer tissues from Chinese patients remain largely unknown. In this study, we compared miRNA expression patterns in 65 pairs of prostate cancer and para-cancer tissues by RNA sequencing and found that miR-182-5p was the most up-regulated miRNA in prostate cancer tissues. The result was validated using realtime PCR in 18 pairs of prostate cancer and para-cancer tissues. In in vitro analysis, it was confirmed that miR-182-5p promotes prostate cancer cell proliferation, invasion and migration and inhibitmore » apoptosis. In addition, the androgen receptor directly regulated the transcription of miR-182-5p, which could target to the 3′UTR of ARRDC3 mRNA and affect the expression of ARRDC3 and its downstream gene ITGB4. For the in vivo experiment, miR-182-5p overexpression also promoted the growth and progression of prostate cancer tumors. In this regard, we suggest that miR-182-5p may be a key androgen receptor-regulated factor that contributes to the development and metastasis of Chinese prostate cancers and may be a potential target for the early diagnosis and therapeutic studies of prostate cancer. -- Highlights: •miR-182-5p is the mostly up-regulated miRNA in Chinese prostate cancer. •miR-182-5p is regulated by androgen receptor. •miR-182-5p promotes prostate cancer progression. •miR-182-5p regulates ARRDC3/ITGB4 pathway.« less

Prostate cancer and inflammation: the evidence

PubMed Central

Sfanos, Karen S; De Marzo, Angelo M

2014-01-01

Chronic inflammation is now known to contribute to several forms of human cancer, with an estimated 20% of adult cancers attributable to chronic inflammatory conditions caused by infectious agents, chronic noninfectious inflammatory diseases and / or other environmental factors. Indeed, chronic inflammation is now regarded as an ‘enabling characteristic’ of human cancer. The aim of this review is to summarize the current literature on the evidence for a role for chronic inflammation in prostate cancer aetiology, with a specific focus on recent advances regarding the following: (i) potential stimuli for prostatic inflammation; (ii) prostate cancer immunobiology; (iii) inflammatory pathways and cytokines in prostate cancer risk and development; (iv) proliferative inflammatory atrophy (PIA) as a risk factor lesion to prostate cancer development; and (v) the role of nutritional or other antiinflammatory compounds in reducing prostate cancer risk. PMID:22212087

Clinical Usefulness of the Histoculture Drug Response Assay for Prostate Cancer and Benign Prostate Hypertrophy (BPH).

PubMed

Hoffman, Robert M

2018-01-01

The histoculture drug response assay (HDRA) has been adapted to determine androgen sensitivity in Gelfoam histoculture of human benign prostatic tissue as well as prostate cancer. Gelfoam histoculture was used to measure androgen-independent and androgen-dependent growth of benign and malignant prostate tissue. The androgen-sensitivity index was significantly higher in 23 paired specimens of prostate cancer compared to benign prostate hypertrophy (BPH). Genistein decreased the androgen-sensitivity index of BPH and prostate cancer in Gelfoam ® histoculture in a dose-dependent manner.

Effectiveness of the combined evaluation of KLK3 genetics and free-to-total prostate specific antigen ratio for prostate cancer diagnosis.

PubMed

Zambon, Carlo-Federico; Prayer-Galetti, Tommaso; Basso, Daniela; Padoan, Andrea; Rossi, Elisa; Secco, Silvia; Pelloso, Michela; Fogar, Paola; Navaglia, Filippo; Moz, Stefania; Zattoni, Filiberto; Plebani, Mario

2012-10-01

Of serum prostate specific antigen variability 40% depends on inherited factors. We ascertained whether the knowledge of KLK3 genetics would enhance prostate specific antigen diagnostic performance in patients with clinical suspicion of prostate cancer. We studied 1,058 men who consecutively underwent prostate biopsy for clinical suspicion of prostate cancer. At histology prostate cancer was present in 401 cases and absent in 657. Serum total prostate specific antigen and the free-to-total prostate specific antigen ratio were determined. Four polymorphisms of the KLK3 gene (rs2569733, rs2739448, rs925013 and rs2735839) and 1 polymorphism of the SRD5A2 gene (rs523349) were studied. The influence of genetics on prostate specific antigen variability was evaluated by multivariate linear regression analysis. The performance of total prostate specific antigen and the free-to-total prostate specific antigen ratio alone or combined with a genetically based patient classification were defined by ROC curve analyses. For prostate cancer diagnosis the free-to-total prostate specific antigen ratio index alone (cutoff 11%) was superior to total prostate specific antigen (cutoff 4 ng/ml) and to free-to-total prostate specific antigen ratio reflex testing (positive predictive value 61%, 43% and 54%, respectively). Prostate specific antigen correlated with KLK3 genetics (rs2735839 polymorphism p = 0.001, and rs2569733, rs2739448 and rs925013 haplotype combination p = 0.003). In patients with different KLK3 genetics 2 optimal free-to-total prostate specific antigen ratio cutoffs (11% and 14.5%) were found. For free-to-total prostate specific antigen ratio values between 11% and 14.5% the prostate cancer probability ranged from 30.0% to 47.4% according to patient genetics. The free-to-total prostate specific antigen ratio is superior to total prostate specific antigen for prostate cancer diagnosis, independent of total prostate specific antigen results. Free-to-total prostate specific antigen ratio findings below 11% are positively associated with prostate cancer and those above 14.5% are negatively associated with prostate cancer, while the interpretation of those between 11% and 14.5% is improved by patient KLK3 genetic analysis. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

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.

VPAC1-targeted PET/CT scan: improved molecular imaging for the diagnosis of prostate cancer using a novel cell surface antigen.

PubMed

Truong, Hong; Gomella, Leonard G; Thakur, Mathew L; Trabulsi, Edouard J

2018-05-01

Current approaches to prostate cancer screening and diagnosis are plagued with limitations in diagnostic accuracy. There is a compelling need for biomolecular imaging that will not only detect prostate cancer early but also distinguish prostate cancer from benign lesions accurately. In this topic paper, we review evidence that supports further investigation of VPAC1-targeted PET/CT imaging in the primary diagnosis of prostate cancer. A non-systematic review of Medline/PubMed was performed. English language guidelines on prostate cancer diagnosis and management, original articles, and review articles were selected based on their clinical relevance. VPAC1 receptors were overexpressed 1000 times more in prostate cancer than benign prostatic stromal tissue. In vitro and in vivo studies showed that Copper-64 labeled analogs of VPAC1 ligands can be synthesized with high radiochemical efficiency and purity. The radioactive probes had excellent VPAC1 receptor binding specificity and affinity. They had good biochemical stability in vitro and in mouse and human serum. They had minimal urinary excretion, which made them favorable for prostate cancer imaging. Initial feasibility study in men with prostate cancer showed that the probes were safe with no reported adverse reaction. 64 Cu-TP3805 PET/CT detected 98% of prostate cancer lesions and nodal metastasis as confirmed with whole mount histopathological evaluation. VPAC1 receptors are promising targets for biomolecular imaging of primary prostate cancer that can distinguish malignant from benign lesions non-invasively. Further investigations are warranted to validate initial findings and define the clinical utilities of VPAC1-targeted PET imaging for prostate cancer diagnosis and management.

Vegetable and fruit intake after diagnosis and risk of prostate cancer progression.

PubMed

Richman, Erin L; Carroll, Peter R; Chan, June M

2012-07-01

Cruciferous vegetables, tomato sauce and legumes have been associated with reduced risk of incident advanced prostate cancer. In vitro and animal studies suggest these foods may inhibit progression of prostate cancer, but there are limited data in men. Therefore, we prospectively examined whether intake of total vegetables, and specifically cruciferous vegetables, tomato sauce and legumes, after diagnosis reduce risk of prostate cancer progression among 1,560 men diagnosed with non-metastatic prostate cancer and participating in the Cancer of the Prostate Strategic Urologic Research Endeavor, a United States prostate cancer registry. As a secondary analysis, we also examined other vegetable subgroups, total fruit and subgroups of fruits. The participants were diagnosed primarily at community-based clinics and followed from 2004 to 2009. We assessed vegetable and fruit intake via a semi-quantitative food frequency questionnaire, and ascertained prostate cancer outcomes via urologist report and medical records. We observed 134 events of progression (53 biochemical recurrences, 71 secondary treatments likely due to recurrence, 6 bone metastases and 4 prostate cancer deaths) during 3,171 person-years. Men in the fourth quartile of post-diagnostic cruciferous vegetable intake had a statistically significant 59% decreased risk of prostate cancer progression compared to men in the lowest quartile (hazard ratio (HR): 0.41; 95% confidence interval (CI): 0.22, 0.76; p-trend: 0.003). No other vegetable or fruit group was statistically significantly associated with risk of prostate cancer progression. In conclusion, cruciferous vegetable intake after diagnosis may reduce risk of prostate cancer progression. Copyright © 2011 UICC.

Studying circulating prostate cancer cells by in-vivo flow cytometer

NASA Astrophysics Data System (ADS)

Guo, Jin; Gu, Zhengqin; Chen, Tong; Wang, Cheng; Wei, Xunbin

2012-03-01

Prostate cancer is the most common malignancy in American men and the second leading cause of deaths from cancer, after lung cancer. The tumor usually grows slowly and remains confined to the gland for many years. As the cancer advances, however, it can metastasize throughout other areas of the body, such as the bones, lungs, and liver. Surgical resection, hormonal therapy, chemotherapy and radiation therapy are the foundation of current prostate cancer therapies. Treatments for prostate cause both short- and long-term side effects that may be difficult to accept. Molecular mechanisms of prostate cancer metastasis need to be understood better and new therapies must be developed to selectively target to unique characteristics of cancer cell growth and metastasis. We have developed the "in vivo microscopy" to study the mechanisms that govern prostate cancer cell spread through the microenvironment in vivo in real-time confocal near-infrared fluorescence imaging. A recently developed "in vivo flow cytometer" and optical imaging are used to assess prostate cancer cell spreading and the circulation kinetics of prostate cancer cells. We have measured the depletion kinetics of cancer cells with different metastatic potential. Interestingly, more invasive PC-3 prostate cancer cells are depleted faster from the circulation than LNCaP cells.

Serum cholesterol and risk of high-grade prostate cancer: results from the REDUCE study.

PubMed

Jamnagerwalla, Juzar; Howard, Lauren E; Allott, Emma H; Vidal, Adriana C; Moreira, Daniel M; Castro-Santamaria, Ramiro; Andriole, Gerald L; Freeman, Michael R; Freedland, Stephen J

2017-12-27

Epidemiologic evidence for a serum cholesterol-prostate cancer link is mixed. Prostate-specific antigen (PSA) is positively correlated with cholesterol, potentially increasing PSA-driven biopsy recommendations in men with high cholesterol, though biopsy compliance may be lower in men with comorbid conditions. These potential biases may affect PSA-driven biopsy rates and subsequent prostate cancer detection in men with high serum cholesterol. Our objective was to test the association between serum cholesterol and prostate cancer risk in men receiving PSA independent, study-mandated prostate biopsies. We conducted a post hoc analysis of data from 4974 non-statin users in REDUCE, a randomized trial in men with elevated PSA and a negative baseline biopsy. Men underwent 2- and 4-year trial-mandated prostate biopsies. Associations between baseline serum levels of total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and prostate cancer risk, overall and by Gleason grade (<7 vs. ≥7), were examined using multivariable logistic regression. High total serum cholesterol was associated with an increased risk of high-grade prostate cancer diagnosis (OR per 10 mg/dL 1.05; 95% CI 1.00-1.09; p = 0.048), but cholesterol was unrelated to either overall or low-grade prostate cancer risk (p-values >0.185). There was no association between serum LDL and overall, low- or high-grade prostate cancer risk (p-values >0.137). In contrast, elevated serum HDL was associated with increased risk of both overall (OR per 10 mg/dL 1.08; 95% CI 1.01-1.16; p = 0.033) and high-grade prostate cancer (OR per 10 mg/dL 1.14; 95% CI 1.01-1.28; p = 0.034). In REDUCE, where all men received PSA independent, trial-mandated biopsies thus ensuring complete prostate cancer ascertainment, high total serum cholesterol and high HDL were associated with increased risk of high-grade prostate cancer, supporting a cholesterol-prostate cancer link.

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.

Seventh Joint Meeting of K-J-CaP and CaPSURE: extending the global initiative to improve prostate cancer management

PubMed Central

Akaza, Hideyuki; Kim, Choung Soo; Carroll, Peter; Choi, In Young; Chung, Byung Ha; Cooperberg, Matthew R.; Hirao, Yoshihiko; Hinotsu, Shiro; Horie, Shigeo; Lee, Ji Youl; Namiki, Mikio; Ng, Chi-Fai; Onozawa, Mizuki; Ozono, Seiichiro; Ueno, Satoru; Umbas, Rainy; Ye, Dingwei; Zhu, Gang

2014-01-01

This report summarizes the presentations and discussions that took place at the Seventh Joint Meeting of the Korea–Japan Study Group of Prostate Cancer (K-J-CaP) and the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) held in Seoul, Korea, in September 2013. The original J-CaP and CaPSURE Joint Initiative has now been established since 2007 and since the initial collaboration between research teams in the United States (US) and Japan, the project has expanded to include several other Asian countries. The objective of the initiative is to analyze and compare data for prostate cancer patients in the participating countries, looking at similarities and differences in patient management and outcomes. Until now the focus has been primarily on data generated within J-CaP and CaPSURE, both large-scale, longitudinal, observational databases of prostate cancer patients in Japan and the US, respectively. This year’s meeting was hosted for the first time in Korea which has recently established its own national database–K-CaP–to add to the wealth of data generated by J-CaP and CaPSURE. As a newly-developed database, K-CaP has also provided a valuable ‘template’ for other countries, such as China and Indonesia, planning to establish their own national databases and this will ultimately allow greater opportunities for international data comparisons. A range of topics was discussed at this Seventh Joint Meeting including comparison of outcomes following androgen deprivation therapy or radical prostatectomy in patients with localized prostate cancer, the use of active surveillance as a treatment option and the triggers for intervention when employing this regimen, patient quality of life during treatment, the impact of comorbidities on outcomes, and a comparison of recent outcomes data between J-CaP and CaPSURE. The participants recognized that prostate cancer was now a global disease and therefore major insights into understanding and improving the management of this condition would arise from global interactions such as this joint initiative. PMID:26153555

Seventh Joint Meeting of K-J-CaP and CaPSURE: extending the global initiative to improve prostate cancer management.

PubMed

Akaza, Hideyuki; Kim, Choung Soo; Carroll, Peter; Choi, In Young; Chung, Byung Ha; Cooperberg, Matthew R; Hirao, Yoshihiko; Hinotsu, Shiro; Horie, Shigeo; Lee, Ji Youl; Namiki, Mikio; Ng, Chi-Fai; Onozawa, Mizuki; Ozono, Seiichiro; Ueno, Satoru; Umbas, Rainy; Ye, Dingwei; Zhu, Gang

2014-01-01

This report summarizes the presentations and discussions that took place at the Seventh Joint Meeting of the Korea-Japan Study Group of Prostate Cancer (K-J-CaP) and the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) held in Seoul, Korea, in September 2013. The original J-CaP and CaPSURE Joint Initiative has now been established since 2007 and since the initial collaboration between research teams in the United States (US) and Japan, the project has expanded to include several other Asian countries. The objective of the initiative is to analyze and compare data for prostate cancer patients in the participating countries, looking at similarities and differences in patient management and outcomes. Until now the focus has been primarily on data generated within J-CaP and CaPSURE, both large-scale, longitudinal, observational databases of prostate cancer patients in Japan and the US, respectively. This year's meeting was hosted for the first time in Korea which has recently established its own national database-K-CaP-to add to the wealth of data generated by J-CaP and CaPSURE. As a newly-developed database, K-CaP has also provided a valuable 'template' for other countries, such as China and Indonesia, planning to establish their own national databases and this will ultimately allow greater opportunities for international data comparisons. A range of topics was discussed at this Seventh Joint Meeting including comparison of outcomes following androgen deprivation therapy or radical prostatectomy in patients with localized prostate cancer, the use of active surveillance as a treatment option and the triggers for intervention when employing this regimen, patient quality of life during treatment, the impact of comorbidities on outcomes, and a comparison of recent outcomes data between J-CaP and CaPSURE. The participants recognized that prostate cancer was now a global disease and therefore major insights into understanding and improving the management of this condition would arise from global interactions such as this joint initiative.

Prostate cancer in Germany among migrants from the Former Soviet Union

PubMed Central

Winkler, Volker; Holleczek, Bernd; Stegmaier, Christa; Becher, Heiko

2012-01-01

Background In Germany, prostate cancer is the leading cause of cancer and the third leading cause of death from cancer in males. We investigate prostate cancer in Gernmany among migrants from the Former Soviet Union (FSU) and compare them to indigenous German population with regard to prostate cancer incidence, mortality and longitudinal effects. Methods Data were obtained from two migrant cohorts residing in the federal states of North Rhine Westphalia (n=34,393) and Saarland (n=18,619). Vital status was ascertained through local population registries. Causes of death were obtained from the federal statistical office or from local health authorities. Cancer incidence of the Saarland cohort was derived from the Saarland Cancer Registry using record linkage. Results From 1990 to 2005 we observed 3360 deaths of which 28 were due to prostate cancer. In the Saarland cohort 35 men were diagnosed with prostate cancer during the respective period. Migrants had lower prostate cancer incidence (SIR 0.74 (95% CI: 0.52–1.03)) and mortality (SMR 0.57 (95% CI: 0.38–0.83)) compared to the German population. Multivariate analysis showed a strong age effect on incidence meaning young migrants (below age 60) were diagnosed significantly more often with prostate cancer compared to Germans of the same age. However, mortality did not show any effects. Discussion Lower prostate cancer mortality and incidence among migrants may reflect an ongoing situation in the FSU. Additionally, longitudinal analysis did not reveal convergence of migrant prostate cancer to German rates as expected from lifestyle driven cancer sites. Therefore, our results support the hypothesis of a genetic effect on prostate cancer risk. PMID:22229025

Prostate Cancer, Nutrition, and Dietary Supplements (PDQ®)—Patient Version

Cancer.gov

Prostate Cancer, Nutrition, and Dietary Supplements summary discusses the use of nutrition and dietary supplements for preventing or treating prostate cancer. Learn more about the use of complementary therapies for prostate cancer in this expert-reviewed summary.

Survival in prostate cancer prevention trial detailed

Cancer.gov

In the NCI-sponsored Prostate Cancer Prevention Trial, initial findings from a decade ago showed that the drug finasteride significantly reduced the risk of prostate cancer, but among those who did develop prostate cancer, paradoxically, the drug was asso

Molecular mechanisms of curcumin and its semisynthetic analogues in prostate cancer prevention and treatment.

PubMed

Jordan, Brian C; Mock, Charlotta D; Thilagavathi, Ramasamy; Selvam, Chelliah

2016-05-01

Primary prostate cancer, also known as prostate adenocarcinoma (PCa), is a devastating cancer in men worldwide. Europe and developing countries of Asia have fewer reported cases of prostate cancer compared to increasing cases in the United States with higher incidence in Black men. Risk factors associated with prostate cancer are aging, genetics, lifestyle, high body mass index as well as carcinogenic exposure to carbon-containing fuels, tobacco, and charbroiled meats. Hormone therapy and radical prostatectomy are commonly implemented treatments. The >20.000 prostate cancer deaths of 2013 suggest that there exists a need for enhanced chemopreventive and therapeutic agents for prostate cancer treatment. Fruits, vegetables, and red wines contain high levels of polyphenolic levels. Consumption of these products may provide chemoprevetion of PCa. Curcumin, the major compound from the turmeric rhizome Curcuma longa has long been used for medicinal purposes as an antiseptic and wound healing. This review focuses on curcumin's therapeutic effectiveness in vitro and in vivo in prostate cancer models. The review will highlight the mechanisms of actions of curcumin in the signaling pathways of prostate cancer. Published by Elsevier Inc.

Prostate cancer prevention agent development: Criteria and pipeline for candidate chemoprevention agents.

PubMed

Nelson, W G; Wilding, G

2001-04-01

Epidemiologic data suggest that prostate cancer morbidity and mortality ought to be preventable. New insights into the molecular pathogenesis of prostate cancer offer new opportunities for the discovery of prostate cancer chemoprevention drugs and new challenges for their development. Established pathways that lead to US Food and Drug Administration (FDA) approval of drugs for advanced prostate cancer may not be appropriate for the development of drugs for prostate cancer chemoprevention. For example, large randomized clinical trials designed to test the efficacy of new chemoprevention drugs on prostate cancer survival in the general population are likely to be conducted at great expense and take many years, threatening to increase commercial development risks while decreasing exclusive marketing revenues. As a consequence, to accelerate progress in research, new validated surrogate and strategic clinical trial endpoints, and new clinical trial designs featuring more precisely defined high-risk clinical trial cohorts, are needed. In this review, 10 criteria for prostate cancer chemoprevention agent development are offered and the pipeline of new prostate cancer chemoprevention drug candidates is considered.

MRI-Derived Cellularity Index as a Potential Noninvasive Imaging Biomarker of Prostate Cancer

DTIC Science & Technology

2014-10-01

previously diagnosed with prostate cancer via standard transrectal ultrasound guided prostate biopsy after prostate specific antigen (PSA) elevation or...around 70% and specificity of 55% (72). Functional MR techniques enhance detection, grading, and staging of prostate cancer through the use of dynamic...and specificity in the diagnosis of prostate cancer by increasing tumor conspicuity on DWI or quantitative ADC maps. How- ever, hemorrhage, inflammatory

Long non-coding RNA lnc-MX1-1 is associated with poor clinical features and promotes cellular proliferation and invasiveness in prostate cancer

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

Jiang, Chen-Yi; Gao, Yuan; Wang, Xing-Jie

Long non-coding RNAs (lncRNAs) are emerging as key molecules in human cancer genesis and progression, including prostate cancer. Large amount of lncRNAs have been found that differentially expressed between prostate cancer tissues and normal prostate tissues. Whether these lncRNAs could serve as a novel biomarker for prostate cancer diagnosis or prognosis, and their biological functions in prostate cancer need further investigation. In the present study, we identified that lncRNA lnc-MX1-1 is over-expressed in prostate cancer tissues compared with their adjacent normal prostate tissues by gene expression array profiling. The expression of lnc-MX1-1 in 60 prostate cancer cases was determined bymore » real-time quantitative PCR and the correlations between lnc-MX1-1 expression and patients' clinical features were further analyzed. Next, we impaired lnc-MX1-1 expression using RNAi in LNCaP and 22Rv1 prostate cancer cells to explore the effects of lnc-MX1-1 on proliferation and invasiveness of the cells. Our results showed that there was a significant association between over-expression of lnc-MX1-1 and patients' clinical features such as PSA, Gleason score, metastasis, and recurrence free survival. Moreover, knockdown of lnc-MX1-1 reduced both proliferation and invasiveness of LNCaP and 22Rv1 cells. In conclusion, the results suggest that lnc-MX1-1 may serve as a potential biomarker and therapeutic target for prostate cancer. - Highlights: • LncRNA lnc-MX1-1 is up-regulated in prostate cancer. • Overexpression of lnc-MX1-1 is correlated with poor prostate cancer clinical features. • Knockdown of lnc-MX1-1 reduces proliferation and invasiveness of prostate cancer cells.« less

Renal Capsule Xenografting and Subcutaneous Pellet Implantation for the Evaluation of Prostate Carcinogenesis and Benign Prostatic Hyperplasia

PubMed Central

Nicholson, Tristan M.; Uchtmann, Kristen S.; Valdez, Conrad D.; Theberge, Ashleigh B.; Miralem, Tihomir; Ricke, William A.

2013-01-01

New therapies for two common prostate diseases, prostate cancer (PrCa) and benign prostatic hyperplasia (BPH), depend critically on experiments evaluating their hormonal regulation. Sex steroid hormones (notably androgens and estrogens) are important in PrCa and BPH; we probe their respective roles in inducing prostate growth and carcinogenesis in mice with experiments using compressed hormone pellets. Hormone and/or drug pellets are easily manufactured with a pellet press, and surgically implanted into the subcutaneous tissue of the male mouse host. We also describe a protocol for the evaluation of hormonal carcinogenesis by combining subcutaneous hormone pellet implantation with xenografting of prostate cell recombinants under the renal capsule of immunocompromised mice. Moreover, subcutaneous hormone pellet implantation, in combination with renal capsule xenografting of BPH tissue, is useful to better understand hormonal regulation of benign prostate growth, and to test new therapies targeting sex steroid hormone pathways. PMID:24022657

Integrating evidence and individual preferences using a web-based multi-criteria decision analytic tool: an application to prostate cancer screening.

PubMed

Cunich, Michelle; Salkeld, Glenn; Dowie, Jack; Henderson, Joan; Bayram, Clare; Britt, Helena; Howard, Kirsten

2011-01-01

Annalisa© (AL) is a web-based decision-support template grounded in multi-criteria decision analysis (MCDA). It uses a simple expected value algorithm to calculate a score for each option by taking into account the individual's preferences for different criteria (as importance weights) and the evidence of the performance of each option on each criterion. Given the uncertainty surrounding the trade offs between benefits and harms for prostate cancer screening, this topic was chosen as the vehicle to introduce this new decision-support template. The aim of the study was to introduce a new decision-support template, AL, and to develop and pilot a decision-support tool for prostate cancer screening using it. A decision-support tool for prostate cancer screening (ALProst) was implemented in the AL template. ALProst incorporated evidence on both the benefits and the potential harms of prostate cancer screening (the 'attributes') from published randomized controlled trials (RCTs). Individual weights for each attribute were elicited during interviews. By combining the individual's preferences and the evidence, the best option for the user was identified on the basis of quantified scores. A convenience sample of computer-proficient primary-care physicians (general practitioners [GPs] in Australia) from the Sydney Metropolitan area (Australia) were invited to complete a face-to-face interview involving the decision-support tool. Preference for undergoing prostate-specific antigen testing for prostate cancer, both personally and for their patients, was sought prior to seeing the tool. After gaining hands-on experience with using the tool, GPs were asked to comment on the merits of the template and the tool. Preference for presenting the benefits of prostate cancer screening as the relative or absolute risk reduction in prostate cancer-specific mortality was also sought. Of 60 GPs approached, ten (six men and four women) completed an interview (16.7% response rate). Most GPs agreed/strongly agreed with positive statements about the ease with which they could use AL (seven GPs), and understand the information in, and format of, AL (nine and eight, respectively). Eight agreed/strongly agreed that ALProst would be a useful tool for discussing prostate cancer screening with their patients. GPs were also asked to nominate difficult clinical decisions that they, and their patients, have had to make; responses included cancer screening (including prostate cancer); treating patients with multiple illnesses/diseases; managing multiple cardiovascular disease risk factors; and managing patients who are receiving multiple medications. The common element was the need to consider multiple factors in making these complex decisions. AL is distinguishable from most other decision-support templates available today by its underlying conceptual framework, MCDA, and its power to combine individual preferences with evidence to derive the best option for the user quantitatively. It therefore becomes potentially useful for all decisions at all levels in the healthcare system. Moreover, it will provide a universal graphic 'language' that can overcome the burden to patients of encountering a plethora of widely varying decision aids for different conditions during their lifetime.

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.

DNA Methylation in Promoter Region as Biomarkers in Prostate Cancer

PubMed Central

Yang, Mihi; Park, Jong Y.

2013-01-01

The prostate gland is the most common site of cancer and the second leading cause of cancer death in American men. Recent emerging molecular biological technologies help us to know that epigenetic alterations such as DNA methylation within the regulatory (promoter) regions of genes are associated with transcriptional silencing in cancer. Promoter hypermethylation of critical pathway genes could be potential biomarkers and therapeutic targets for prostate cancer. In this chapter, we updated current information on methylated genes associated with the development and progression of prostate cancer. Over 40 genes have been investigated for methylation in promoter region in prostate cancer. These methylated genes are involved in critical pathways, such as DNA repair, metabolism, and invasion/metastasis. The role of hypermethylated genes in regulation of critical pathways in prostate cancer is discussed. These findings may provide new information of the pathogenesis, the exciting potential to be predictive and to provide personalized treatment of prostate cancer. Indeed, some epigenetic alterations in prostate tumors are being translated into clinical practice for therapeutic use. PMID:22359288

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.

A Cancer-Indicative microRNA Pattern in Normal Prostate Tissue

PubMed Central

Hellwinkel, Olaf J. C.; Sellier, Christina; Sylvester, Yu-Mi Jessica; Brase, Jan C.; Isbarn, Hendrik; Erbersdobler, Andreas; Steuber, Thomas; Sültmann, Holger; Schlomm, Thorsten; Wagner, Christina

2013-01-01

We analyzed the levels of selected micro-RNAs in normal prostate tissue to assess their potential to indicate tumor foci elsewhere in the prostate. Histologically normal prostate tissue samples from 31 prostate cancer patients and two cancer negative control groups with either unsuspicious or elevated prostate specific antigen (PSA) levels (14 and 17 individuals, respectively) were analyzed. Based on the expression analysis of 157 microRNAs in a pool of prostate tissue samples and information from data bases/literature, we selected eight microRNAs for quantification by real-time polymerase chain reactions (RT-PCRs). Selected miRNAs were analyzed in histologically tumor-free biopsy samples from patients and healthy controls. We identified seven microRNAs (miR-124a, miR-146a & b, miR-185, miR-16 and let-7a & b), which displayed significant differential expression in normal prostate tissue from men with prostate cancer compared to both cancer negative control groups. Four microRNAs (miR-185, miR-16 and let-7a and let-7b) remained to significantly discriminate normal tissues from prostate cancer patients from those of the cancer negative control group with elevated PSA levels. The transcript levels of these microRNAs were highly indicative for the presence of cancer in the prostates, independently of the PSA level. Our results suggest a microRNA-pattern in histologically normal prostate tissue, indicating prostate cancer elsewhere in the organ. PMID:23459235

Screening for Prostate Cancer Starting at Age 50-54. A Population-based Cohort Study

PubMed Central

Carlsson, Sigrid; Assel, Melissa; Ulmert, David; Gerdtsson, Axel; Hugosson, Jonas; Vickers, Andrew; Lilja, Hans

2016-01-01

Background Current prostate cancer screening guidelines conflict with respect to the age at which to initiate screening. Objective To evaluate the effect of prostate-specific antigen (PSA) screening, versus zero screening, starting at age 50-54, on prostate cancer mortality. Design, Setting, and Participants This is a population-based cohort study comparing 3,479 men aged 50 through 54 randomized to PSA-screening in the Göteborg population-based prostate cancer screening trial, initiated in 1995, versus 4,060 unscreened men aged 51 to 55 providing cryopreserved blood in the population-based Malmö Preventive Project in the pre-PSA era, during 1982-1985. Outcome measures and Statistical Analysis Cumulative incidence and incidence rate ratios of prostate cancer diagnosis, metastasis, and prostate cancer death. Results and Limitation At 17 years, regular PSA-screening in Göteborg of men in their early 50s carried a more than 2-fold higher risk of prostate cancer diagnosis compared to the unscreened men in Malmö (IRR 2.56, 95% CI 2.18, 3.02), but resulted in a substantial decrease in risk of metastases (IRR 0.43, 95% CI 0.22, 0.79) and prostate cancer death (IRR 0.29, 95% CI 0.11, 0.67). There were 57 fewer prostate cancer deaths per 10,000 men (95% CI 22, 92) in the screened group. At 17 years, the number needed to invite to PSA-screening and the number needed to diagnose to prevent one prostate cancer death was 176 and 16, respectively. The study is limited by lack of treatment information and the comparison of two different birth cohorts. Conclusions PSA screening for prostate cancer can decrease prostate cancer mortality among men aged 50–54, with NNI and NND comparable to those previously reported from the European Randomized Study of Screening for Prostate Cancer for men aged 55-69 years, at similar follow-up. Guideline groups could consider whether guidelines for PSA screening should recommend starting no later than at ages 50-54. Trial registration The Göteborg randomized population-based prostate cancer screening trial is registered with the ISRCTN registry (isrctn.com). Identifier: ISRCTN54449243. PMID:27084245

Combining lymphovascular invasion with reactive stromal grade predicts prostate cancer mortality.

PubMed

Saeter, Thorstein; Vlatkovic, Ljiljana; Waaler, Gudmund; Servoll, Einar; Nesland, Jahn M; Axcrona, Karol; Axcrona, Ulrika

2016-09-01

Previous studies suggest that lymphovascular invasion (LVI) has a weak and variable effect on prognosis. It is uncertain whether LVI, determined by diagnostic prostate biopsy, predicts prostate cancer death. Data from experimental studies have indicated that carcinoma-associated fibroblasts in the reactive stroma could promote LVI and progression to metastasis. Thus, combining LVI with reactive stromal grade may identify prostate cancer patients at high risk of an unfavorable outcome. The purpose of the present study was to examine if LVI, determined by diagnostic biopsy, alone and in combination with reactive stromal grade could predict prostate cancer death. This population-based study included 283 patients with prostate cancer diagnosed by needle biopsy in Aust-Agder County (Norway) from 1991 to 1999. Clinical data were obtained by medical charts review. Two uropathologists evaluated LVI and reactive stromal grade. The endpoint was prostate cancer death. Patients with LVI had marginally higher risk of prostate cancer death compared to patients without LVI (hazard ratio: 1.8, P-value = 0.04). LVI had a stronger effect on prostate cancer death risk when a high reactive stromal grade was present (hazard ratio: 16.0, P-value <0.001). Therefore, patients with concomitant LVI and high reactive stromal grade were at particularly high risk for prostate cancer death. Evaluating LVI together with reactive stromal grade on diagnostic biopsies could be used to identify patients at high risk of death from prostate cancer. Prostate 76:1088-1094, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Oncogenic LINE-1 Retroelements Sustain Prostate Tumor Cells and Promote Metastatic Progression

DTIC Science & Technology

2015-10-01

elements in prostate cancer contribute to its progression by activating oncogenic DNA sequences, or silencing tumor suppressor like sequences. We have...prostate cancer cells. Experiments are ongoing to determine if PIWIL-1 expression in prostate cancer cells will reduce their growth, thereby providing...proof of principle for future gene-based therapeutics for this cancer . 15. SUBJECT TERMS Prostate cancer , LINE-1, PIWIL-1, retrotransposons 16

Prostate cancer progression and mortality: a review of diet and lifestyle factors.

PubMed

Peisch, Sam F; Van Blarigan, Erin L; Chan, June M; Stampfer, Meir J; Kenfield, Stacey A

2017-06-01

To review and summarize evidence on the role of diet and lifestyle factors and prostate cancer progression, with a specific focus on habits after diagnosis and the risk of subsequent disease recurrence, progression, or death. Given the well-documented heterogeneity of prostate cancer and the long survivorship of the majority of diagnoses, our goal was to summarize and describe modifiable risk factors for clinically relevant prostate cancer. We focused where possible on epidemiologic studies of post-diagnostic habits and prostate cancer progression, defined as recurrence (e.g., PSA risk, secondary treatment), metastasis, or death. Where data were limited, we also describe evidence on risk factors and indicators of prostate cancer aggressiveness at diagnosis. A variety of dietary and lifestyle factors appear to affect prostate cancer progression. Several generally widely recommended lifestyle factors such as not smoking, maintaining a healthy body weight, and regular vigorous physical exercise also appear to affect prostate cancer progression. Several dietary factors, such as tomato sauce/lycopene, cruciferous vegetables, healthy sources of vegetable fats, and coffee, may also have a role in reducing risk of prostate cancer progression. Diet and lifestyle factors, in particular exercise and smoking cessation, may reduce the risk of prostate cancer progression and death. These promising findings warrant further investigation, as their overall impact might be large.

[Concomitant oncopathological changes in the prostate of urinary bladder cancer patients undergoing radical cystoprostateectomy].

PubMed

Komyakov, B K; Sergeev, A V; Fadeev, V A; Ismailov, K I; Ulyanov, A Yu; Shmelev, A Yu; Onoshko, M V

2017-09-01

To determine the incidence of spreading bladder transitional cell carcinoma and primary adenocarcinoma to the prostate in patients with bladder cancer undergoing radical cystectomy. From 1995 to 2016, 283 men underwent radical cystectomy with removal of the bladder, perivesical tissue, prostate, seminal vesicles and pelvic lymph nodes. Prostate sparing cystectomy was performed in 45 (13.7%) patients. The whole prostate and the apex of the prostate were preserved in 21 (6.4%) and 24 (7.3%) patients, respectively. The spread of transitional cell cancer of the bladder to the prostate occurred in 50 (15.2%) patients. Twelve (3.6%) patients were found to have primary prostate adenocarcinoma. Clinically significant prostate cancer was diagnosed in 4 (33.3%) patients. We believe that the high oncological risk of prostate sparing cystectomy, despite some functional advantages, dictates the need for complete removal of the prostate in the surgical treatment of bladder cancer.

Incidental Metastatic Melanoma Identified on 68Ga-Prostate-Specific Membrane Antigen PET/CT for Metastatic Prostate Cancer.

PubMed

Snow, Hayden A; Hofman, Michael S; Mitchell, Catherine A; Gyorki, David E; Smith, Myles J F

2018-07-01

A 78-year-old man with a history of surgically treated prostate cancer and melanoma underwent Ga-prostate-specific membrane antigen (PSMA) PET/CT for biochemical recurrence of his prostate cancer. This revealed locoregionally recurrent prostate cancer and a separate PSMA-avid nodule in his left arm. Subsequent F-FDG PET/CT and excision confirmed this to be an in-transit melanoma metastasis. Prostate-specific membrane antigen PET/CT has become a widely used and valuable tool in the assessment of prostate cancer, particularly biochemically recurrent. Uptake of PSMA has been described in a multitude of different benign and malignant conditions, but it has only rarely been documented in melanoma.

Roswell Park Cancer Institute / Howard University Prostate Cancer Scholars Program

DTIC Science & Technology

2015-10-01

1 AWARD NUMBER: W81XWH-14-1-0531 TITLE: Roswell Park Cancer Institute / Howard University Prostate Cancer Scholars Program PRINCIPAL...TITLE AND SUBTITLE Roswell Park Cancer Institute/Howard University Prostate Cancer 5a. CONTRACT NUMBER W81XWH-14-1-0531 Cancer Scholars Program 5b...ABSTRACT The Roswell Park/Howard University Prostate Cancer Scholars Program is designed to encourage students from under-represented minority groups

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.

Depletion kinetics of circulating prostate cancer cells studied by in vivo flow cytometer

NASA Astrophysics Data System (ADS)

Liu, Guangda; Guo, Jin; Li, Yan; Chen, Yun; Gu, Zhengqin; Chen, Tong; Wang, Cheng; Wei, Xunbin

2010-11-01

Prostate cancer is the most common malignancy in American men and the second leading cause of deaths from cancer, after lung cancer. The tumor usually grows slowly and remains confined to the gland for many years. During this time, the tumor produces little or no symptoms or outward signs. As the cancer advances, however, it can metastasize throughout other areas of the body, such as the bones, lungs, and liver. Surgical resection, hormonal therapy, chemotherapy and radiation therapy are the foundation of current prostate cancer therapies. Treatments for prostate cause both short- and long-term side effects that may be difficult to accept. Molecular mechanisms of prostate cancer metastasis need to be understood better and new therapies must be developed to selectively target to unique characteristics of cancer cell growth and metastasis. We have developed the "in vivo microscopy" to study the mechanisms that govern prostate cancer cell spread through the microenvironment in vivo in real-time confocal nearinfrared fluorescence imaging. A recently developed "in vivo flow cytometer" and optical imaging are used to assess prostate cancer cell spreading and the circulation kinetics of prostate cancer cells. A real- time quantitative monitoring of circulating prostate cancer cells by the in vivo flow cytometer will be useful to assess the effectiveness of the potential therapeutic interventions.

Studying depletion kinetics of circulating prostate cancer cells by in vivo flow cytometer

NASA Astrophysics Data System (ADS)

Liu, Guangda; Gu, Zhengqin; Guo, Jin; Li, Yan; Chen, Yun; Chen, Tong; Wang, Cheng; Wei, Xunbin

2011-03-01

Prostate cancer is the most common malignancy in American men and the second leading cause of deaths from cancer, after lung cancer. The tumor usually grows slowly and remains confined to the gland for many years. During this time, the tumor produces little or no symptoms or outward signs. As the cancer advances, however, it can metastasize throughout other areas of the body, such as the bones, lungs, and liver. Surgical resection, hormonal therapy, chemotherapy and radiation therapy are the foundation of current prostate cancer therapies. Treatments for prostate cause both short- and long-term side effects that may be difficult to accept. Molecular mechanisms of prostate cancer metastasis need to be understood better and new therapies must be developed to selectively target to unique characteristics of cancer cell growth and metastasis. We have developed the "in vivo microscopy" to study the mechanisms that govern prostate cancer cell spread through the microenvironment in vivo in real-time confocal near-infrared fluorescence imaging. A recently developed "in vivo flow cytometer" and optical imaging are used to assess prostate cancer cell spreading and the circulation kinetics of prostate cancer cells. A real- time quantitative monitoring of circulating prostate cancer cells by the in vivo flow cytometer will be useful to assess the effectiveness of the potential therapeutic interventions.

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

What do men understand about lifetime risk following genetic testing? The effect of context and numeracy.

PubMed

Rolison, Jonathan J; Hanoch, Yaniv; Miron-Shatz, Talya

2012-07-01

Genetic testing for gene mutations associated with specific cancers provides an opportunity for early detection, surveillance, and intervention (Smith, Cokkinides, & Brawley, 2008). Lifetime risk estimates provided by genetic testing refer to the risk of developing a specific disease within one's lifetime, and evidence suggests that this is important for the medical choices people make, as well as their future family and financial plans. The present studies tested whether adult men understand the lifetime risks of prostate cancer informed by genetic testing. In 2 experiments, adult men were asked to interpret the lifetime risk information provided in statements about risks of prostate cancer. Statement format was manipulated such that the most appropriate interpretation of risk statements referred to an absolute risk of cancer in experiment 1 and a relative risk in experiment 2. Experiment 1 revealed that few men correctly interpreted the lifetime risks of cancer when these refer to an absolute risk of cancer, and numeracy levels positively predicted correct responding. The proportion of correct responses was greatly improved in experiment 2 when the most appropriate interpretation of risk statements referred instead to a relative rather than an absolute risk, and numeracy levels were less involved. Understanding of lifetime risk information is often poor because individuals incorrectly believe that these refer to relative rather than absolute risks of cancer.

Prostate Health Index improves multivariable risk prediction of aggressive prostate cancer.

PubMed

Loeb, Stacy; Shin, Sanghyuk S; Broyles, Dennis L; Wei, John T; Sanda, Martin; Klee, George; Partin, Alan W; Sokoll, Lori; Chan, Daniel W; Bangma, Chris H; van Schaik, Ron H N; Slawin, Kevin M; Marks, Leonard S; Catalona, William J

2017-07-01

To examine the use of the Prostate Health Index (PHI) as a continuous variable in multivariable risk assessment for aggressive prostate cancer in a large multicentre US study. The study population included 728 men, with prostate-specific antigen (PSA) levels of 2-10 ng/mL and a negative digital rectal examination, enrolled in a prospective, multi-site early detection trial. The primary endpoint was aggressive prostate cancer, defined as biopsy Gleason score ≥7. First, we evaluated whether the addition of PHI improves the performance of currently available risk calculators (the Prostate Cancer Prevention Trial [PCPT] and European Randomised Study of Screening for Prostate Cancer [ERSPC] risk calculators). We also designed and internally validated a new PHI-based multivariable predictive model, and created a nomogram. Of 728 men undergoing biopsy, 118 (16.2%) had aggressive prostate cancer. The PHI predicted the risk of aggressive prostate cancer across the spectrum of values. Adding PHI significantly improved the predictive accuracy of the PCPT and ERSPC risk calculators for aggressive disease. A new model was created using age, previous biopsy, prostate volume, PSA and PHI, with an area under the curve of 0.746. The bootstrap-corrected model showed good calibration with observed risk for aggressive prostate cancer and had net benefit on decision-curve analysis. Using PHI as part of multivariable risk assessment leads to a significant improvement in the detection of aggressive prostate cancer, potentially reducing harms from unnecessary prostate biopsy and overdiagnosis. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

Prostate Cancer in Deceased Liver Donors.

PubMed

Skalski, M; Gierej, B; Ziarkiewicz-Wróblewska, B; Hołówko, W; Krawczyk, M

2016-06-01

Prostate cancer is the second most common malignant tumor (13%) among male subjects in Poland. The aim of this study was to assess the prevalence of prostate cancer in a group of deceased liver donors. A total of 784 liver procurement attempts from deceased donors were performed in the Department of General, Transplant and Liver Surgery, Medical University of Warsaw, from January 1, 2012, to April 1, 2015; 700 grafts were actually used in a liver transplant. A retrospective analysis was performed based on these data. Among male donors (n = 486 [62%]), there were 30 (6.2%) cases of a frozen biopsy of the prostate performed before making the decision regarding liver graft utilization. In the group of 30 donors who underwent prostate examination, 3 (10%) were diagnosed as having prostate cancer of a moderate invasive stage. In 2 other cases, fresh frozen section suggested prostate cancer; however, this fact was not confirmed in routine section. liver transplantation was not performed in these cases of suspicion of prostate cancer (5 of 30 [17%]) in the frozen biopsy specimens. The difference between groups of donors with prostate cancer and benign pathology of the prostate gland according to prostate-specific antigen serum concentration (P = .578) or age (P = .730) was not statistically significant. Increased prostate-specific antigen serum concentrations without a diagnosis of prostate cancer in histopathologic examinations should not be an independent contraindication for performing organ transplantation. Nevertheless, for recipient safety, even when prostate cancer is only suspected in the frozen biopsy sample, the procured organ should not be used for transplantation. Copyright © 2016 Elsevier Inc. All rights reserved.

Paucity of PD-L1 expression in prostate cancer: innate and adaptive immune resistance.

PubMed

Martin, A M; Nirschl, T R; Nirschl, C J; Francica, B J; Kochel, C M; van Bokhoven, A; Meeker, A K; Lucia, M S; Anders, R A; DeMarzo, A M; Drake, C G

2015-12-01

Primary prostate cancers are infiltrated with programmed death-1 (PD-1) expressing CD8+ T-cells. However, in early clinical trials, men with metastatic castrate-resistant prostate cancer did not respond to PD-1 blockade as a monotherapy. One explanation for this unresponsiveness could be that prostate tumors generally do not express programmed death ligand-1 (PD-L1), the primary ligand for PD-1. However, lack of PD-L1 expression in prostate cancer would be surprising, given that phosphatase and tensin homolog (PTEN) loss is relatively common in prostate cancer and several studies have shown that PTEN loss correlates with PD-L1 upregulation--constituting a mechanism of innate immune resistance. This study tested whether prostate cancer cells were capable of expressing PD-L1, and whether the rare PD-L1 expression that occurs in human specimens correlates with PTEN loss. Human prostate cancer cell lines were evaluated for PD-L1 expression and loss of PTEN by flow cytometry and western blotting, respectively. Immunohistochemical (IHC) staining for PTEN was correlated with PD-L1 IHC using a series of resected human prostate cancer samples. In vitro, many prostate cancer cell lines upregulated PD-L1 expression in response to inflammatory cytokines, consistent with adaptive immune resistance. In these cell lines, no association between PTEN loss and PD-L1 expression was apparent. In primary prostate tumors, PD-L1 expression was rare, and was not associated with PTEN loss. These studies show that some prostate cancer cell lines are capable of expressing PD-L1. However, in human prostate cancer, PTEN loss is not associated with PD-L1 expression, arguing against innate immune resistance as a mechanism that mitigates antitumor immune responses in this disease.

The Stockholm-3 (STHLM3) Model can Improve Prostate Cancer Diagnostics in Men Aged 50-69 yr Compared with Current Prostate Cancer Testing.

PubMed

Eklund, Martin; Nordström, Tobias; Aly, Markus; Adolfsson, Jan; Wiklund, Peter; Brandberg, Yvonne; Thompson, James; Wiklund, Fredrik; Lindberg, Johan; Presti, Joseph C; StLezin, Mark; Clements, Mark; Egevad, Lars; Grönberg, Henrik

2016-11-23

Prostate cancer screening is associated with low specificity, unnecessary biopsies, and overdiagnosis. We have previously shown that the Stockholm-3 model (S3M) can reduce biopsies compared with using prostate-specific antigen (PSA) ≥3ng/ml as an indication for biopsy. Urologists in today's current prostate cancer testing (CPT) have access to numerous variables in addition to PSA (eg, age, ethnicity, family history, free PSA, PSA velocity, digital rectal examination, and prostate volume) to support biopsy decisions. We estimated the number of prostate cancers diagnosed and prostate biopsies performed if S3M replaced CPT in Stockholm, Sweden, by comparing biopsy results in 56 282 men who underwent PSA testing according to CPT in Stockholm in 2011 with the 47 688 men enrolled in the STHLM3 validation cohort 2012-2015. With the same sensitivity as CPT to diagnose Gleason score ≥7 prostate cancer, S3M was estimated to reduce the number of men biopsied by 53% (95% confidence interval [CI]: 41-65%), avoid 76% (95% CI: 67-81%) of negative biopsies, and reduce Gleason score 6 cancers by 23% (95% CI: 6-40%). S3M has the potential to improve prostate cancer diagnostics by better selecting men with high risk of GS ≥7 prostate cancer. We modeled the effect the Stockholm-3 model would have on prostate cancer diagnostics if it replaced current clinical practice. We found that Stockholm-3 model may substantially reduce the number of biopsies, while maintaining the same sensitivity to diagnose clinically significant prostate cancer. Copyright © 2016. Published by Elsevier B.V.

Modulation of AKR1C2 by curcumin decreases testosterone production in prostate cancer.

PubMed

Ide, Hisamitsu; Lu, Yan; Noguchi, Takahiro; Muto, Satoru; Okada, Hiroshi; Kawato, Suguru; Horie, Shigeo

2018-04-01

Intratumoral androgen biosynthesis has been recognized as an essential factor of castration-resistant prostate cancer. The present study investigated the effects of curcumin on the inhibition of intracrine androgen synthesis in prostate cancer. Human prostate cancer cell lines, LNCaP and 22Rv1 cells were incubated with or without curcumin after which cell proliferation was measured at 0, 24, 48 and 72 hours, respectively. Prostate tissues from the transgenic adenocarcinoma of the mouse prostate (TRAMP) model were obtained after 1-month oral administration of 200 mg/kg/d curcumin. Testosterone and dihydrotestosterone concentrations in LNCaP prostate cancer cells were determined through LC-MS/MS assay. Curcumin inhibited cell proliferation and induced apoptosis of prostate cancer cells in a dose-dependent manner. Curcumin decreased the expression of steroidogenic acute regulatory proteins, CYP11A1 and HSD3B2 in prostate cancer cell lines, supporting the decrease of testosterone production. After 1-month oral administration of curcumin, Aldo-Keto reductase 1C2 (AKR1C2) expression was elevated. Simultaneously, decreased testosterone levels in the prostate tissues were observed in the TRAMP mice. Meanwhile, curcumin treatments considerably increased the expression of AKR1C2 in prostate cancer cell lines, supporting the decrease of dihydrotestosterone. Taken together, these results suggest that curcumin's natural bioactive compounds could have potent anticancer properties due to suppression of androgen production, and this could have therapeutic effects on prostate cancer. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

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).

Prostate Cancer

MedlinePlus

... breast cancer (BRCA1 or BRCA2) or a very strong family history of breast cancer, your risk of prostate cancer may be higher. Obesity. Obese men diagnosed with prostate cancer may be more likely ...

[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.

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.

Zinc Intake and Risk of Prostate Cancer: Case-Control Study and Meta-Analysis.

PubMed

Mahmoud, Abeer M; Al-Alem, Umaima; Dabbous, Firas; Ali, Mohamed M; Batai, Ken; Shah, Ebony; Kittles, Rick A

2016-01-01

Zinc is an essential dietary element that has been implicated in the pathogenesis of prostate cancer, a cancer that disproportionately affects men of African descent. Studies assessing the association of zinc intake and prostate cancer have yielded inconsistent results. Furthermore, very little is known about the relationship between zinc intake and prostate cancer among African Americans. We examined the association between self-reported zinc intake and prostate cancer in a hospital-based case-control study of African Americans. We then compared our results with previous studies by performing a meta-analysis to summarize the evidence regarding the association between zinc and prostate cancer. Newly diagnosed African American men with histologically confirmed prostate cancer (n = 127) and controls (n = 81) were recruited from an urban academic urology clinic in Washington, DC. Controls had higher zinc intake, with a mean of 14 mg/day versus 11 mg/day for cases. We observed a non-significant, non-linear increase in prostate cancer when comparing tertiles of zinc intake (OR <6.5 vs 6.5-12.5mg/day 1.8, 95% CI: 0.6,5.6; OR <6.5 vs >12.5mg/day 1.3, 95% CI: 0.2,6.5). The pooled estimate from 17 studies (including 3 cohorts, 2 nested case-control, 11 case-control studies, and 1 randomized clinical trial, with a total of 111,199 participants and 11,689 cases of prostate cancer) was 1.07hi vs lo 95% CI: 0.98-1.16. Using a dose-response meta-analysis, we observed a non-linear trend in the relationship between zinc intake and prostate cancer (p for nonlinearity = 0.0022). This is the first study to examine the relationship between zinc intake in black men and risk of prostate cancer and systematically evaluate available epidemiologic evidence about the magnitude of the relationship between zinc intake and prostate cancer. Despite of the lower intake of zinc by prostate cancer patients, our meta-analysis indicated that there is no evidence for an association between zinc intake and prostate cancer.

Interleukin-30: A novel microenvironmental hallmark of prostate cancer progression.

PubMed

Di Carlo, Emma

2014-01-01

Metastatic prostate cancer is a leading cause of cancer-related death in men worldwide. We have recently discovered that IL-30 shapes the microenvironment of prostate cancer and tumor-draining lymph nodes to favor tumor progression. IL-30 supports tumor growth in vitro, and IL-30 expression in prostate cancer patients is associated with high tumor grade and metastatic stage of disease. Thus, IL-30 may constitute a valuable target for modern therapeutic approaches to hamper prostate cancer progression.

Analysis of spatial heterogeneity in normal epithelium and preneoplastic alterations in mouse prostate tumor models

PubMed Central

Valkonen, Mira; Ruusuvuori, Pekka; Kartasalo, Kimmo; Nykter, Matti; Visakorpi, Tapio; Latonen, Leena

2017-01-01

Cancer involves histological changes in tissue, which is of primary importance in pathological diagnosis and research. Automated histological analysis requires ability to computationally separate pathological alterations from normal tissue with all its variables. On the other hand, understanding connections between genetic alterations and histological attributes requires development of enhanced analysis methods suitable also for small sample sizes. Here, we set out to develop computational methods for early detection and distinction of prostate cancer-related pathological alterations. We use analysis of features from HE stained histological images of normal mouse prostate epithelium, distinguishing the descriptors for variability between ventral, lateral, and dorsal lobes. In addition, we use two common prostate cancer models, Hi-Myc and Pten+/− mice, to build a feature-based machine learning model separating the early pathological lesions provoked by these genetic alterations. This work offers a set of computational methods for separation of early neoplastic lesions in the prostates of model mice, and provides proof-of-principle for linking specific tumor genotypes to quantitative histological characteristics. The results obtained show that separation between different spatial locations within the organ, as well as classification between histologies linked to different genetic backgrounds, can be performed with very high specificity and sensitivity. PMID:28317907

'You ain't going to say...I've got a problem down there': workplace-based prostate health promotion with men.

PubMed

Dolan, Alan; Staples, Victoria; Summer, Sylvie; Hundt, Gillian Lewando

2005-12-01

Prostate health has emerged as a key health issue for men. Nearly 10,000 men die from prostate cancer each year and many more live with non-cancerous, but debilitating, prostate conditions. Despite the widespread prevalence, evidence suggests that men lack knowledge about male cancers and conditions, and are more likely to ignore signs and delay seeking help. Health promotion with men in the workplace is, therefore, increasingly being advocated as an important way of providing men with health information and encouraging them to see a health professional where appropriate. However, there has not been a developed account of men's views on health promotion within the workplace. This paper presents the findings of a small-scale qualitative study that explored men's perceptions and experiences of three different workplace-based health promotion interventions to improve prostate health awareness and their attitudes towards the workplace as an appropriate setting for promoting men's health. This paper shows that men generally welcomed a workplace-based health promotion campaign targeted specifically at them. However, the masculine 'culture' of the workplace, where concerns about health were likely to be met with ridicule rather than concern, was one important factor in understanding these men's views of different health promotion interventions.

Optimizing heat shock protein expression induced by prostate cancer laser therapy through predictive computational models

NASA Astrophysics Data System (ADS)

Rylander, Marissa N.; Feng, Yusheng; Zhang, Yongjie; Bass, Jon; Stafford, Roger J.; Hazle, John D.; Diller, Kenneth R.

2006-07-01

Thermal therapy efficacy can be diminished due to heat shock protein (HSP) induction in regions of a tumor where temperatures are insufficient to coagulate proteins. HSP expression enhances tumor cell viability and imparts resistance to chemotherapy and radiation treatments, which are generally employed in conjunction with hyperthermia. Therefore, an understanding of the thermally induced HSP expression within the targeted tumor must be incorporated into the treatment plan to optimize the thermal dose delivery and permit prediction of the overall tissue response. A treatment planning computational model capable of predicting the temperature, HSP27 and HSP70 expression, and damage fraction distributions associated with laser heating in healthy prostate tissue and tumors is presented. Measured thermally induced HSP27 and HSP70 expression kinetics and injury data for normal and cancerous prostate cells and prostate tumors are employed to create the first HSP expression predictive model and formulate an Arrhenius damage model. The correlation coefficients between measured and model predicted temperature, HSP27, and HSP70 were 0.98, 0.99, and 0.99, respectively, confirming the accuracy of the model. Utilization of the treatment planning model in the design of prostate cancer thermal therapies can enable optimization of the treatment outcome by controlling HSP expression and injury.

Multiple Time-Point 68Ga-PSMA I&T PET/CT for Characterization of Primary Prostate Cancer: Value of Early Dynamic and Delayed Imaging.

PubMed

Schmuck, Sebastian; Mamach, Martin; Wilke, Florian; von Klot, Christoph A; Henkenberens, Christoph; Thackeray, James T; Sohns, Jan M; Geworski, Lilli; Ross, Tobias L; Wester, Hans-Juergen; Christiansen, Hans; Bengel, Frank M; Derlin, Thorsten

2017-06-01

The aims of this study were to gain mechanistic insights into prostate cancer biology using dynamic imaging and to evaluate the usefulness of multiple time-point Ga-prostate-specific membrane antigen (PSMA) I&T PET/CT for the assessment of primary prostate cancer before prostatectomy. Twenty patients with prostate cancer underwent Ga-PSMA I&T PET/CT before prostatectomy. The PET protocol consisted of early dynamic pelvic imaging, followed by static scans at 60 and 180 minutes postinjection (p.i.). SUVs, time-activity curves, quantitative analysis based on a 2-tissue compartment model, Patlak analysis, histopathology, and Gleason grading were compared between prostate cancer and benign prostate gland. Primary tumors were identified on both early dynamic and delayed imaging in 95% of patients. Tracer uptake was significantly higher in prostate cancer compared with benign prostate tissue at any time point (P ≤ 0.0003) and increased over time. Consequently, the tumor-to-nontumor ratio within the prostate gland improved over time (2.8 at 10 minutes vs 17.1 at 180 minutes p.i.). Tracer uptake at both 60 and 180 minutes p.i. was significantly higher in patients with higher Gleason scores (P < 0.01). The influx rate (Ki) was higher in prostate cancer than in reference prostate gland (0.055 [r = 0.998] vs 0.017 [r = 0.996]). Primary prostate cancer is readily identified on early dynamic and static delayed Ga-PSMA ligand PET images. The tumor-to-nontumor ratio in the prostate gland improves over time, supporting a role of delayed imaging for optimal visualization of prostate cancer.

Race does not predict the development of metastases in men with nonmetastatic castration-resistant prostate cancer.

PubMed

Whitney, Colette A; Howard, Lauren E; Amling, Christopher L; Aronson, William J; Cooperberg, Matthew R; Kane, Christopher J; Terris, Martha K; Freedland, Stephen J

2016-12-15

Although race is associated with prostate cancer progression in early stage disease, once men have advanced disease, it is unclear whether race continues to predict a poor outcome. The authors hypothesized that, in an equal-access setting among patients with castration-resistant prostate cancer (CRPC) and no known metastases (M0/Mx), black men would receive imaging tests at similar rates as nonblack men (ie, there would be an equal opportunity to detect metastases) but would have a higher risk of metastatic disease. In total, 837 men who were diagnosed with M0/Mx CRPC during 2000 through 2014 from 5 Veterans Affairs hospitals in the SEARCH (Shared Equal Access Regional Cancer Hospital) database were analyzed. Data on all imaging tests after CRPC diagnosis were collected, including date, type, and outcome. Multivariable Cox models were used to test associations between race and the time to first metastasis, first bone metastasis, first bone scan, second bone scan among men who had a negative first bone scan, and overall survival. Black men (n = 306) were equally as likely as nonblack men (n = 531) to receive a first and second bone scan after a diagnosis of CRPC. There were no significant differences in the risk of developing any metastases, bone metastases, time to bone scans, or overall survival between black men and nonblack men (all P > .2). The lack of racial differences in the development of metastases and scanning practices observed in this study suggests that, once men have a diagnosis of M0/Mx CRPC, race may not be a prognostic factor. Efforts to understand prostate cancer racial disparities may derive greater benefit by focusing on the risk of developing prostate cancer and on the outcomes of men who have early stage disease. Cancer 2016;122:3848-3855. © 2016 American Cancer Society. © 2016 American Cancer Society.

Cultural factors associated with the intent to be screened for prostate cancer among adult men in a rural Kenyan community.

PubMed

Mutua, Kinyao; Pertet, Anne M; Otieno, Careena

2017-11-23

The aim of this study was to determine cultural factors associated with prostate cancer screening intent among adult Kenyan African men. A cross-sectional quantitative study with an analytic design was carried out in a randomly selected sample of 155 adult men aged 25-98 years living in a rural community in Kenya. Constructs from the Theory of Planned Behaviour were used to guide this study. A 5 -point Likert scale was used to assess fatalistic beliefs, fear, perceived benefits, and family influence. A structured questionnaire was used to collect quantitative data at the household level. Only 2.4% of the study participants had been screened for prostate cancer. About 2/3rd (64%) of the participants felt that they were at risk of getting prostate cancer; 44% intended to be screened within the following 6 months. Mean scores on a 5-point Likert scale indicated: strong beliefs in the benefits of prostate screening (4.2 (±SD .8), men aged over 40 were not perceived to be at risk of getting prostate cancer (1.3 ± .6), relatively high fatalistic beliefs of prostate cancer screening (3.6 (±SD .8), high degree of fear or apprehension of prostate cancer screening (3.2 (±SD 1.2), and a high level of influence of family members in prostate cancer screening (3.9 (±SD 1.0). The Wald criterion demonstrated that only family influence made a significant contribution to the intent to screen for prostate cancer (p = 0.031). Age, education, marital status, fatalism, fear, and benefit of screening were not associated with the intent to screen for prostate cancer. Strong beliefs of the benefits of prostate screening tended to be surpassed by relatively high fatalistic beliefs and fear or apprehension in prostate cancer screening. The family plays an important role in influencing decision making related to prostate cancer screening in Africans.

Individual and mutual predictors of marital satisfaction among prostate cancer patients and their spouses.

PubMed

Chien, Ching-Hui; Chuang, Cheng-Keng; Liu, Kuan-Lin; Huang, Xuan-Yi; Pang, See-Tong; Wu, Chun-Te; Chang, Ying-Hsu; Liu, Hsueh-Erh

2017-12-01

To determine the individual and mutual predictors of the marital satisfaction of couples in which the husband experienced prostate cancer. Marital satisfaction of patients with prostate cancer has been insufficiently studied in Asian countries as compared with Western countries. This study used a prospective and repeated-measures design. Seventy Taiwanese couples in which the husband had prostate cancer completed measures at 6 and 12 months post-treatment. Assessments of physical symptoms, marital satisfaction, coping behaviour and psychological distress were made. Multiple linear regression was used to analyse the data. The marital satisfaction of patients with prostate cancer and that of their spouses were significantly correlated. At 6 months, spouses' marital satisfaction, patients' appraisal of prostate cancer as a threat and patients' serum prostate-specific antigen levels were found to be the predictors of patients' marital satisfaction. Furthermore, patients' marital satisfaction and their spouses' psychological distress were predictors of spouses' marital satisfaction. At 12 months, spouses' marital satisfaction and patients' appraisal of prostate cancer as harm were predictors of patients' marital satisfaction. Finally, spouses' marital satisfaction (at 6 months) and appraisal of prostate cancer as a threat were predictors of spouses' marital satisfaction. At 6 months post-treatment, patients' and spouses' marital satisfaction will influence each other. However, at 12 months, patients' marital satisfaction exerts an insignificant effect on spouses' marital satisfaction. Moreover, patients' serum prostate-specific antigen level or the negative appraisal of prostate cancer affects their marital satisfaction. Spouses' marital satisfaction is affected by psychological distress and their negative appraisal of prostate cancer. The results can be used to develop interventions for prostate cancer couples. Such an intervention can be used to modify couples' appraisal of prostate cancer by changing incorrect thinking or to ease the psychological distress to improve marital satisfaction. © 2017 John Wiley & Sons Ltd.

The relationship between total testosterone levels and prostate cancer: a review of the continuing controversy.

PubMed

Klap, Julia; Schmid, Marianne; Loughlin, Kevin R

2015-02-01

For many years it was believed that higher total testosterone contributed to prostate cancer and caused rapid cancer growth. International guidelines consider that adequate data are not available to determine whether there is additional risk of prostate cancer from testosterone replacement. Numerous studies with multiple designs and contradictory conclusions have investigated the relationship between total testosterone and prostate cancer development. To establish current knowledge in this field we reviewed the literature on total testosterone and the subsequent risk of prostate cancer as well as the safety of exogenous testosterone administration in patients with a history of prostate cancer. We searched the literature to identify articles from 1994 to 2014 related to the relationship between total testosterone and prostate cancer. Emphasis was given to prospective studies, series with observational data and randomized, controlled trials. Case reports were excluded. Articles on testosterone replacement safety were selected by patient population (under active surveillance or with a prostate cancer history). We organized our results according to the relationship between total testosterone and prostate cancer, including 1) the possible link between low total testosterone and prostate cancer, 2) the effect of high levels and 3) the absence of any link. Finally, we summarized studies of the risk of exogenous testosterone administration in patients already diagnosed with prostate cancer, treated or on active surveillance. We selected 45 articles of the relationship between total testosterone and prostate cancer, of which 18 and 17 showed a relationship to low and high total testosterone, respectively, and 10 showed no relation. Total testosterone was defined according to the definition in each article. Contradictory findings have been reported, largely due to the disparate methodologies used in many studies. Most studies did not adhere to professional society guidelines on total testosterone measurements. One of 18 series of low total testosterone and prostate cancer adhered to published guidelines while none of 17 showing a relationship of high total testosterone to prostate cancer and only 1 of 10 that identified no relationship between total testosterone and prostate cancer adhered to measurements recommended in the guidelines. In 11 studies the risk of exogenous testosterone was examined in patients with a prostate cancer history. Many studies were limited by small cohort size and brief followup. However, overall this literature suggests that the risk of exogenous testosterone replacement in patients with prostate cancer appears to be small. The relationship between total testosterone and prostate cancer has been an area of interest among physicians for decades. Conflicting results have been reported on the relationship between total testosterone and subsequent prostate cancer. Much of this controversy appears to be based on conflicting study designs, definitions and methodologies. To date no prospective study with sufficient power has been published to unequivocally resolve the issue. The preponderance of studies of the safety of exogenous testosterone in men with a prostate cancer history suggests that there is little if any risk. However, because the risk has not proved to be zero, the most prudent course is to follow such men with regular prostate specific antigen measurements and digital rectal examinations. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

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,

3 CFR 8552 - Proclamation 8552 of August 31, 2010. National Prostate Cancer Awareness Month, 2010

Code of Federal Regulations, 2011 CFR

2011-01-01

... Prostate Cancer Awareness Month, 2010 8552 Proclamation 8552 Presidential Documents Proclamations Proclamation 8552 of August 31, 2010 Proc. 8552 National Prostate Cancer Awareness Month, 2010By the President... last decade, prostate cancer is still the second leading cause of cancer deaths among men in the United...

3 CFR 8855 - Proclamation 8855 of August 31, 2012. National Prostate Cancer Awareness Month, 2012

Code of Federal Regulations, 2013 CFR

2013-01-01

... Prostate Cancer Awareness Month, 2012 8855 Proclamation 8855 Presidential Documents Proclamations Proclamation 8855 of August 31, 2012 Proc. 8855 National Prostate Cancer Awareness Month, 2012By the President of the United States of America A Proclamation Prostate cancer is among the most common cancers for...

The influence of family history on cognitive heuristics, risk perceptions, and prostate cancer screening behavior.

PubMed

McDowell, Michelle E; Occhipinti, Stefano; Chambers, Suzanne K

2013-11-01

To examine how family history of prostate cancer, risk perceptions, and heuristic decision strategies influence prostate cancer screening behavior. Men with a first-degree family history of prostate cancer (FDRs; n = 207) and men without a family history (PM; n = 239) completed a Computer Assisted Telephone Interview (CATI) examining prostate cancer risk perceptions, PSA testing behaviors, perceptions of similarity to the typical man who gets prostate cancer (representativeness heuristic), and availability of information about prostate cancer (availability heuristic). A path model explored family history as influencing the availability of information about prostate cancer (number of acquaintances with prostate cancer and number of recent discussions about prostate cancer) to mediate judgments of risk and to predict PSA testing behaviors and family history as a moderator of the relationship between representativeness (perceived similarity) and risk perceptions. FDRs reported greater risk perceptions and a greater number of PSA tests than did PM. Risk perceptions predicted increased PSA testing only in path models and was significant only for PM in multi-Group SEM analyses. Family history moderated the relationship between similarity perceptions and risk perceptions such that the relationship between these variables was significant only for FDRs. Recent discussions about prostate cancer mediated the relationships between family history and risk perceptions, and the number of acquaintances men knew with prostate cancer mediated the relationship between family history and PSA testing behavior. Family history interacts with the individuals' broader social environment to influence risk perceptions and screening behavior. Research into how risk perceptions develop and what primes behavior change is crucial to underpin psychological or public health intervention that seeks to influence health decision making.

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.

Prostate cancer incidence in Australia correlates inversely with solar radiation.

PubMed

Loke, Tim W; Seyfi, Doruk; Sevfi, Doruk; Khadra, Mohamed

2011-11-01

What's known on the subject? and What does the study add? Increased sun exposure and blood levels of vitamin D have been postulated to be protective against prostate cancer. This is controversial. We investigated the relationship between prostate cancer incidence and solar radiation in non-urban Australia, and found a lower incidence in regions receiving more sunlight. In landmark ecological studies, prostate cancer mortality rates have been shown to be inversely related to ultraviolet radiation exposure. Investigators have hypothesised that ultraviolet radiation acts by increasing production of vitamin D, which inhibits prostate cancer cells in vitro. However, analyses of serum levels of vitamin D in men with prostate cancer have failed to support this hypothesis. This study has found an inverse correlation between solar radiation and prostate cancer incidence in Australia. Our population (previously unstudied) represents the third group to exhibit this correlation. Significantly, the demographics and climate of Australia differ markedly from those of previous studies conducted on men in the United Kingdom and the United States. • To ascertain if prostate cancer incidence rates correlate with solar radiation among non-urban populations of men in Australia. • Local government areas from each state and territory were selected using explicit criteria. Urban areas were excluded from analysis. • For each local government area, prostate cancer incidence rates and averaged long-term solar radiation were obtained. • The strength of the association between prostate cancer incidence and solar radiation was determined. • Among 70 local government areas of Australia, age-standardized prostate cancer incidence rates for the period 1998-2007 correlated inversely with daily solar radiation averaged over the last two decades. •  There exists an association between less solar radiation and higher prostate cancer incidence in Australia. © 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.

The Genomic Evolution of Prostate Cancer

DTIC Science & Technology

2017-06-01

management and grant writing skills. 15. SUBJECT TERMS Cancer genetics , tumor evolution, tumor heterogeneity, prostate cancer, exome sequencing 16...aggressive disease, it is unclear if the genetic alterations more common in late disease are present early on, but at low frequency, or if they only...from localized to metastatic prostate cancer. 2. KEYWORDS: Cancer genetics , tumor evolution, tumor heterogeneity, prostate cancer, exome sequencing

Cancer Localization in the Prostate with F-18 Fluorocholine Positron Emission Tomography

DTIC Science & Technology

2007-01-01

INTRODUCTION Prostate cancer is the second leading cause of cancer death in American men over 50 years of age. Ultrasound - guided prostate biopsy is...currently the most common method for diagnosing and localizing cancer in the prostate. However, even when standard 6 or 12 needle biopsy templates... needles employed (1, 2). While progress has been made in the detection of primary prostate cancer using imaging techniques such as ultrasound and

Descriptive characteristics of prostate cancer in patients with a history of primary male breast cancer - a SEER analysis.

PubMed

Abhyankar, Nikita; Hoskins, Kent F; Abern, Michael R; Calip, Gregory S

2017-09-25

Current evidence on risk of prostate cancer following a diagnosis of male breast cancer is limited and guidance for screening in this potentially higher-risk population remainsunclear. Our objective was to quantify prostate cancer risk in men diagnosed with breast cancer. We identified men diagnosed with first primary breast cancer between 1988 and 2012 using the Surveillance, Epidemiology and End Results Program registry databases. Men were followed for occurrence of a second primary prostate cancer and secondary outcomes of cancer-specific and overall survival. Stratified analyses were performed by age, breast cancer stage, race, and breast cancer hormone receptor status. Excess risk per 10,000 person-years and standardized incidence ratios (SIR) with 95% confidence intervals (95% CI) were calculated. We used multivaraible Cox proportional hazard models to estimate hazard ratios (HR) and 95% CI for characteristics associated with secondary prostate cancer and survival. From a cohort of 5753 men with breast cancer with median follow up of 4.3 years, we identified 250 cases of second primary prostate cancer. Overall, the incidence of second primary prostate cancer was modestly greater than expected (SIR = 1.12, 95% CI 0.93-1.33), although not statistically significant. Stratified analyses demonstrated associations for men ages 65-74 at the time of breast cancer diagnosis (SIR = 1.34, 95%CI 1.01-1.73), hormone receptor-positive breast cancer (SIR = 1.23, 95%CI 1.11-1.39) or AJCC stage I breast cancer (SIR = 1.36, 95%CI 1.04-1.75) and second primary prostate cancer diagnosis. The incidence of prostate cancer in men with history of breast cancer is similar to the general population. Men with favorable characteristics of their breast cancer were more likely to develop prostate cancer, possibly due to a lower competing risk of breast cancer mortality.

Landmark Trials | Division of Cancer Prevention

Cancer.gov

The studies listed below represent the first major clinical trials to evaluate risk reduction for people at high risk of breast, prostate, lung, colorectal, ovarian, cervical, and lung cancer. Analysis of the data gathered from these large trials continues to contribute valuable understanding about related issues, including screening, patient-reported symptoms, quality of

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.

PHF21B overexpression promotes cancer stem cell-like traits in prostate cancer cells by activating the Wnt/β-catenin signaling pathway.

PubMed

Li, Qiji; Ye, Liping; Guo, Wei; Wang, Min; Huang, Shuai; Peng, Xinsheng

2017-06-23

PHF21B is newly identified to be involved in the tumor progression; however, its biological role and molecular mechanism in prostate cancer have not been defined. This study is aimed to study the role of PHF21B in the progression of prostate cancer. Real-time PCR, immunohistochemistry and western blotting analysis were used to determine PHF21B expression in prostate cancer cell lines and clinical specimens. The role of PHF21B in maintaining prostate cancer stem cell-like phenotype was examined by tumor-sphere formation assay and expression levels of stem cell markers. Luciferase reporter assay, western blot analysis, enzyme-linked immunosorbent assay and ChIP assay were used to determine whether PHF21B activates the Wnt/β-catenin signaling by transcriptionally downregulating SFRP1 and SFRP2. Our results revealed that PHF21B was markedly upregulated in prostate cancer cell lines and tissues. High PHF21B levels predicted poorer recurrence-free survival in prostate cancer patients. Gain-of-function and loss-of-function studies showed that overexpression of PHF21B enhanced, while downregulation suppressed, the cancer stem cell-like phenotype in prostate cancer cells. Xenograft tumor model showed that silencing PHF21B decreased the ability of tumorigenicity in vivo. Notably, Wnt/β-catenin signaling was hyperactivated in prostate cancer cells overexpressing PHF21B, and mediated PHF21B-induced cancer stem cell-like phenotype. Furthermore, PHF21B suppressed repressors of the Wnt/β-catenin signaling cascade, including SFRP1 and SFRP2. These results demonstrated that PHF21B constitutively activated wnt/β-catenin signaling by transcriptionally downregulating SFRP1 and SFRP2, which promotes prostate cancer stem cell-like phenotype. Our results revealed that PHF21B functions as an oncogene in prostate cancer, and may represent a promising prognostic biomarker and an attractive candidate for target therapy of prostate cancer.

Evaluating genetic risk for prostate cancer among Japanese and Latinos

PubMed Central

Cheng, Iona; Chen, Gary K.; Nakagawa, Hidewaki; He, Jing; Wan, Peggy; Laurie, Cathy; Shen, Jess; Sheng, Xin; Pooler, Loreall C.; Crenshaw, Andrew T.; Mirel, Daniel B.; Takahashi, Atsushi; Kubo, Michiaki; Nakamura, Yusuke; Al Olama, Ali Amin; Benlloch, Sara; Donovan, Jenny L.; Guy, Michelle; Hamdy, Freddie C.; Kote-Jarai, Zsofia; Neal, David E.; Wilkens, Lynne R.; Monroe, Kristine R.; Stram, Daniel O.; Muir, Kenneth; Eeles, Rosalind A.; Easton, Douglas F.; Kolonel, Laurence N.; Henderson, Brian E.; Le Marchand, Loïc; Haiman, Christopher A.

2012-01-01

Background There have been few genome-wide association studies (GWAS) of prostate cancer among diverse populations. To search for novel prostate cancer risk variants, we conducted GWAS of prostate cancer in Japanese and Latinos. In addition, we tested prostate cancer risk variants and developed genetic risk models of prostate cancer for Japanese and Latinos. Methods Our first stage GWAS of prostate cancer included Japanese (cases/controls=1,033/1,042) and Latino (cases/controls=1,043/1,057) from the Multiethnic Cohort. Significant associations from stage 1 (P < 1.0×10−4) were examined in silico in GWAS of prostate cancer (stage 2) in Japanese (cases/controls=1,583/3,386) and Europeans (cases/controls=1,854/1,894). Results No novel stage 1 SNPs outside of known risk regions reached genome-wide significance. For Japanese, in stage 1, the most notable putative novel association was seen with 10 SNPs (P<8.0. x10−6) at chromosome 2q33; however, this was not replicated in stage 2. For Latinos, the most significant association was observed with rs17023900 at the known 3p12 risk locus (stage 1: OR=1.45; P=7.01×10−5 and stage 2: OR=1.58; P =3.05×10−7). The majority of the established risk variants for prostate cancer, 79% and 88%, were positively associated with prostate cancer in Japanese and Latinos (stage I), respectively. The cumulative effects of these variants significantly influence prostate cancer risk (OR per allele=1.10; P = 2.71×10−25 and OR=1.07; P = 1.02×10−16 for Japanese and Latinos, respectively). Conclusion and Impact Our GWAS of prostate cancer did not identify novel genome-wide significant variants. However, our findings demonstrate that established risk variants for prostate cancer significantly contribute to risk among Japanese and Latinos. PMID:22923026

Evaluating genetic risk for prostate cancer among Japanese and Latinos.

PubMed

Cheng, Iona; Chen, Gary K; Nakagawa, Hidewaki; He, Jing; Wan, Peggy; Laurie, Cathy C; Shen, Jess; Sheng, Xin; Pooler, Loreall C; Crenshaw, Andrew T; Mirel, Daniel B; Takahashi, Atsushi; Kubo, Michiaki; Nakamura, Yusuke; Al Olama, Ali Amin; Benlloch, Sara; Donovan, Jenny L; Guy, Michelle; Hamdy, Freddie C; Kote-Jarai, Zsofia; Neal, David E; Wilkens, Lynne R; Monroe, Kristine R; Stram, Daniel O; Muir, Kenneth; Eeles, Rosalind A; Easton, Douglas F; Kolonel, Laurence N; Henderson, Brian E; Le Marchand, Loïc; Haiman, Christopher A

2012-11-01

There have been few genome-wide association studies (GWAS) of prostate cancer among diverse populations. To search for novel prostate cancer risk variants, we conducted GWAS of prostate cancer in Japanese and Latinos. In addition, we tested prostate cancer risk variants and developed genetic risk models of prostate cancer for Japanese and Latinos. Our first-stage GWAS of prostate cancer included Japanese (cases/controls = 1,033/1,042) and Latino (cases/controls = 1,043/1,057) from the Multiethnic Cohort (MEC). Significant associations from stage I (P < 1.0 × 10(-4)) were examined in silico in GWAS of prostate cancer (stage II) in Japanese (cases/controls = 1,583/3,386) and Europeans (cases/controls = 1,854/1,894). No novel stage I single-nucleotide polymorphism (SNP) outside of known risk regions reached genome-wide significance. For Japanese, in stage I, the most notable putative novel association was seen with 10 SNPs (P ≤ 8.0 × 10(-6)) at chromosome 2q33; however, this was not replicated in stage II. For Latinos, the most significant association was observed with rs17023900 at the known 3p12 risk locus (stage I: OR = 1.45; P = 7.01 × 10(-5) and stage II: OR = 1.58; P = 3.05 × 10(-7)). The majority of the established risk variants for prostate cancer, 79% and 88%, were positively associated with prostate cancer in Japanese and Latinos (stage I), respectively. The cumulative effects of these variants significantly influence prostate cancer risk (OR per allele = 1.10; P = 2.71 × 10(-25) and OR = 1.07; P = 1.02 × 10(-16) for Japanese and Latinos, respectively). Our GWAS of prostate cancer did not identify novel genome-wide significant variants. However, our findings show that established risk variants for prostate cancer significantly contribute to risk among Japanese and Latinos. ©2012 AACR.

Alcohol consumption and prostate cancer incidence and progression: A Mendelian randomisation study

PubMed Central

Brunner, Clair; Davies, Neil M.; Martin, Richard M.; Eeles, Rosalind; Easton, Doug; Kote‐Jarai, Zsofia; Al Olama, Ali Amin; Benlloch, Sara; Muir, Kenneth; Giles, Graham; Wiklund, Fredrik; Gronberg, Henrik; Haiman, Christopher A.; Schleutker, Johanna; Nordestgaard, Børge G.; Travis, Ruth C.; Neal, David; Donovan, Jenny; Hamdy, Freddie C.; Pashayan, Nora; Khaw, Kay‐Tee; Stanford, Janet L.; Blot, William J.; Thibodeau, Stephen; Maier, Christiane; Kibel, Adam S.; Cybulski, Cezary; Cannon‐Albright, Lisa; Brenner, Hermann; Park, Jong; Kaneva, Radka; Batra, Jyotsna; Teixeira, Manuel R.; Pandha, Hardev

2016-01-01

Prostate cancer is the most common cancer in men in developed countries, and is a target for risk reduction strategies. The effects of alcohol consumption on prostate cancer incidence and survival remain unclear, potentially due to methodological limitations of observational studies. In this study, we investigated the associations of genetic variants in alcohol‐metabolising genes with prostate cancer incidence and survival. We analysed data from 23,868 men with prostate cancer and 23,051 controls from 25 studies within the international PRACTICAL Consortium. Study‐specific associations of 68 single nucleotide polymorphisms (SNPs) in 8 alcohol‐metabolising genes (Alcohol Dehydrogenases (ADHs) and Aldehyde Dehydrogenases (ALDHs)) with prostate cancer diagnosis and prostate cancer‐specific mortality, by grade, were assessed using logistic and Cox regression models, respectively. The data across the 25 studies were meta‐analysed using fixed‐effect and random‐effects models. We found little evidence that variants in alcohol metabolising genes were associated with prostate cancer diagnosis. Four variants in two genes exceeded the multiple testing threshold for associations with prostate cancer mortality in fixed‐effect meta‐analyses. SNPs within ALDH1A2 associated with prostate cancer mortality were rs1441817 (fixed effects hazard ratio, HRfixed = 0.78; 95% confidence interval (95%CI):0.66,0.91; p values = 0.002); rs12910509, HRfixed = 0.76; 95%CI:0.64,0.91; p values = 0.003); and rs8041922 (HRfixed = 0.76; 95%CI:0.64,0.91; p values = 0.002). These SNPs were in linkage disequilibrium with each other. In ALDH1B1, rs10973794 (HRfixed = 1.43; 95%CI:1.14,1.79; p values = 0.002) was associated with prostate cancer mortality in men with low‐grade prostate cancer. These results suggest that alcohol consumption is unlikely to affect prostate cancer incidence, but it may influence disease progression. PMID:27643404

Prostate Cancer Patients' Refusal of Cancer-Directed Surgery: A Statewide Analysis

PubMed Central

Islam, K. M.

2015-01-01

Introduction. Prostate cancer is the most common cancer among men in USA. The surgical outcomes of prostate cancer remain inconsistent. Barriers such as socioeconomic factors may play a role in patients' decision of refusing recommended cancer-directed surgery. Methods. The Nebraska Cancer Registry data was used to calculate the proportion of prostate cancer patients recommended the cancer-directed surgery and the surgery refusal rate. Multivariate logistic regression was applied to analyze the socioeconomic indicators that were related to the refusal of surgery. Results. From 1995 to 2012, 14,876 prostate cancer patients were recommended to undergo the cancer-directed surgery in Nebraska, and 576 of them refused the surgery. The overall refusal rate of surgery was 3.9% over the 18 years. Patients with early-stage prostate cancer were more likely to refuse the surgery. Patients who were Black, single, or covered by Medicaid/Medicare had increased odds of refusing the surgery. Conclusion. Socioeconomic factors were related to the refusal of recommended surgical treatment for prostate cancer. Such barriers should be addressed to improve the utilization of surgical treatment and patients' well-being. PMID:25973276

Prostate Cancer—Patient Version

Cancer.gov

Prostate cancer is the most common cancer among men in the United States. Prostate cancer usually grows very slowly, and finding and treating it before symptoms occur may not improve men’s health. Start here to find information on prostate cancer treatment, research, causes and prevention, screening, and statistics.

Prostate cancer stem cells: from theory to practice.

PubMed

Adamowicz, Jan; Pakravan, Katayoon; Bakhshinejad, Babak; Drewa, Tomasz; Babashah, Sadegh

2017-04-01

None of the generally accepted theories on prostate cancer development can fully explain many distinguishing features of the disease, such as intratumoral heterogeneity, metastatic growth, drug resistance and tumor relapse. Prostate stem cells are a heterogeneous and small subpopulation of self-renewing cells which can actively proliferate in response to changes in the androgen level and give rise to all the cell lineages that build the prostate epithelium. According to the cancer stem cell hypothesis, prostate cancer could be a stem cell disease. Prostate cancer stem cells, which represent only a minimal percentage of the tumor mass, are characterized by a markedly increased clonogenicity and therapeutic resistance. These tumor-initiating cells reside in dynamic niches distributed within the prostate but at a higher concentration in proximal regions of the prostatic ducts. Several markers have been used to identify prostate cancer stem cells. Nevertheless, a definitive profile has not yet been established owing to specificity issues. As cancer stem cells play determining roles in the birth and burst of prostate malignancy, strategies that selectively target them have gained huge clinical attention. Unraveling the mechanisms underlying the physiological functions of cancer stem cells and gaining fundamental insights into their putative involvement in the pathogenesis of prostate tumors provide novel opportunities for the development of efficient and sophisticated therapeutic strategies in the future.

A spatial-temporal approach to surveillance of prostate cancer disparities in population subgroups.

PubMed Central

Hsu, Chiehwen Ed; Mas, Francisco Soto; Miller, Jerry A.; Nkhoma, Ella T.

2007-01-01

BACKGROUND: Prostate cancer mortality disparities exist among racial/ethnic groups in the United States, yet few studies have explored the spatiotemporal trend of the disease burden. To better understand mortality disparities by geographic regions over time, the present study analyzed the geographic variations of prostate cancer mortality by three Texas racial/ethnic groups over a 22-year period. METHODS: The Spatial Scan Statistic developed by Kulldorff et al was used. Excess mortality was detected using scan windows of 50% and 90% of the study period and a spatial cluster size of 50% of the population at risk. Time trend was analyzed to examine the potential temporal effects of clustering. Spatial queries were used to identify regions with multiple racial/ethnic groups having excess mortality. RESULTS: The most likely area of excess mortality for blacks occurred in Dallas-Metroplex and upper east Texas areas between 1990 and 1999; for Hispanics, in central Texas between 1992 and 1996: and for non-Hispanic whites, in the upper south and west to central Texas areas between 1990 and 1996. Excess mortality persisted among all racial/ethnic groups in the identified counties. The second scan revealed that three counties in west Texas presented an excess mortality for Hispanics from 1980-2001. Many counties bore an excess mortality burden for multiple groups. There is no time trend decline in prostate cancer mortality for blacks and non-Hispanic whites in Texas. CONCLUSION: Disparities in prostate cancer mortality among racial/ethnic groups existed in Texas. Central Texas counties with excess mortality in multiple subgroups warrant further investigation. PMID:17304971

A Single Center Evaluation of the Diagnostic Accuracy of Multiparametric Magnetic Resonance Imaging against Transperineal Prostate Mapping Biopsy: An Analysis of Men with Benign Histology and Insignificant Cancer following Transrectal Ultrasound Biopsy.

PubMed

Pal, Raj P; Ahmad, Ros; Trecartan, Shaun; Voss, James; Ahmed, Shaista; Bazo, Alvaro; Lloyd, Jon; Walton, Thomas J

2018-03-01

In this study we evaluated the diagnostic performance of transrectal ultrasound guided biopsy and multiparametric magnetic resonance imaging to detect prostate cancer against transperineal prostate mapping biopsy as the reference test. Transrectal ultrasound guided biopsy, multiparametric magnetic resonance imaging and transperineal prostate mapping biopsy were performed in 426 patients between April 2012 and January 2016. Patients initially underwent systematic 12 core transrectal ultrasound guided biopsy followed 3 months later by 1.5 Tesla, high resolution T2, diffusion-weighted, dynamic contrast enhanced multiparametric magnetic resonance imaging. Two specialist uroradiologists blinded to the results of transperineal prostate mapping biopsy allocated a PI-RADS™ (Prostate Imaging-Reporting and Data System) score to each multiparametric magnetic resonance imaging study. Transperineal prostate mapping biopsy with 5 mm interval sampling, which was performed within 6 months of multiparametric magnetic resonance imaging, served as the reference test. Transrectal ultrasound guided biopsy identified 247 of 426 patients with prostate cancer and 179 of 426 with benign histology. Transperineal prostate mapping biopsy detected prostate cancer in 321 of 426 patients. On transperineal prostate mapping biopsy 94 of 179 patients with benign transrectal ultrasound guided biopsy had prostate cancer and 95 of 247 with prostate cancer on transrectal ultrasound guided biopsy were identified with cancer of higher grade. Using a multiparametric magnetic resonance imaging PI-RADS score of 3 or greater to detect significant prostate cancer, defined as any core containing Gleason 4 + 3 or greater prostate cancer on transperineal prostate mapping biopsy, the ROC AUC was 0.754 (95% CI 0.677-0.819) with 87.0% sensitivity (95% CI 77.3-97.0), 55.3% specificity (95% CI 50.2-60.4) and 97.1% negative predictive value (95% CI 94.8-99.4). Multiparametric magnetic resonance imaging is a more accurate diagnostic test than transrectal ultrasound guided biopsy. However, a significant proportion of ISUP (International Society of Urological Pathology) Grade Group 2 prostate cancer remained undetected following multiparametric magnetic resonance imaging. Although multiparametric magnetic resonance imaging could avoid unnecessary biopsy in many patients with ISUP Grade Group 3 or greater prostate cancer, at less stringent definitions of significant cancer a substantial proportion of prostate cancer would remain undetected after multiparametric magnetic resonance imaging. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Renal donors with prostate cancer, no longer a reason to decline.

PubMed

Dholakia, S; Johns, R; Muirhead, L; Papalois, V; Crane, J

2016-01-01

To fully assess the true risk of prostate cancer transmission in during renal transplantation. A full review of all existing literature relevant to the topic. There has not been a single documented case of transmission of prostate cancer during renal transplant. Prostate cancer in deceased organ donors has an incidence estimated between 3% and 18.5% and over 100 transplants have been performed using organs from donor with proven prostate cancer without issue. Transmission of prostate cancer through kidney transplantation seems very unlikely. The risks of remaining on the waiting list are outweighed by a transmission risk and the potential benefit makes the case to have clear guidelines about donor prostate malignancy when accepting potential organs. Copyright © 2015. Published by Elsevier Inc.

Calcium, magnesium, and whole-milk intakes and high-aggressive prostate cancer in the North Carolina-Louisiana Prostate Cancer Project (PCaP).

PubMed

Steck, Susan E; Omofuma, Omonefe O; Su, L Joseph; Maise, Amanda A; Woloszynska-Read, Anna; Johnson, Candace S; Zhang, Hongmei; Bensen, Jeannette T; Fontham, Elizabeth T H; Mohler, James L; Arab, Lenore

2018-05-01

Calcium and dairy product intakes have been positively associated with prostate cancer risk. An imbalance in concentrations of calcium and magnesium has been associated with multiple chronic diseases, although few studies have examined the relation with prostate cancer aggressiveness. The goal of this study was to examine the association between dietary intakes of calcium and magnesium, the calcium-to-magnesium ratio (Ca:Mg), and dairy products and prostate cancer aggressiveness. Dietary intake was assessed with the use of an interviewer-administered modified National Cancer Institute Diet History Questionnaire in 996 African American and 1064 European American men with a recent histologically confirmed diagnosis of prostate cancer from the North Carolina-Louisiana Prostate Cancer Project (PCaP). High-aggressive disease was defined as Gleason sum ≥8, or prostate-specific antigen (PSA) >20 ng/mL, or Gleason score ≥7 and clinical stage T3-T4. The comparison group was all other prostate cancer cases. Logistic regression was used to determine the adjusted ORs and 95% CIs for high-aggressive prostate cancer by tertile of diet and supplement exposures. There was a positive association across tertiles of dietary Ca:Mg intake, with odds of high-aggressive prostate cancer in the upper tertiles as follows-OR for tertile 2 compared with tertile 1: 1.38 (95% CI: 1.01, 1.88); OR for tertile 3 compared with tertile 1: 1.46 (95% CI: 1.06, 2.02). When stratified by race, the positive association was more pronounced in African American men (OR for tertile 3 compared with tertile 2: 1.62; 95% CI: 1.04, 2.53). Men who reported the highest daily consumption of whole-fat milk had a 74% increased odds of high-aggressive prostate cancer compared with non-whole-fat milk drinkers, which was attenuated after adjustment for potential mediating factors, such as saturated fat and Ca:Mg intake. Among both African American and European American men diagnosed with prostate cancer, a higher Ca:Mg and whole-milk intake were associated with higher odds of high-aggressive prostate cancer. This study was registered at www.clinicaltrials.gov as NCT03289130.

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

A DNA methylation microarray-based study identifies ERG as a gene commonly methylated in prostate cancer.

PubMed

Schwartzman, Jacob; Mongoue-Tchokote, Solange; Gibbs, Angela; Gao, Lina; Corless, Christopher L; Jin, Jennifer; Zarour, Luai; Higano, Celestia; True, Lawrence D; Vessella, Robert L; Wilmot, Beth; Bottomly, Daniel; McWeeney, Shannon K; Bova, G Steven; Partin, Alan W; Mori, Motomi; Alumkal, Joshi

2011-10-01

DNA methylation of promoter regions is a common event in prostate cancer, one of the most common cancers in men worldwide. Because prior reports demonstrating that DNA methylation is important in prostate cancer studied a limited number of genes, we systematically quantified the DNA methylation status of 1505 CpG dinucleotides for 807 genes in 78 paraffin-embedded prostate cancer samples and three normal prostate samples. The ERG gene, commonly repressed in prostate cells in the absence of an oncogenic fusion to the TMPRSS2 gene, was one of the most commonly methylated genes, occurring in 74% of prostate cancer specimens. In an independent group of patient samples, we confirmed that ERG DNA methylation was common, occurring in 57% of specimens, and cancer-specific. The ERG promoter is marked by repressive chromatin marks mediated by polycomb proteins in both normal prostate cells and prostate cancer cells, which may explain ERG's predisposition to DNA methylation and the fact that tumors with ERG DNA methylation were more methylated, in general. These results demonstrate that bead arrays offer a high-throughput method to discover novel genes with promoter DNA methylation such as ERG, whose measurement may improve our ability to more accurately detect prostate cancer.

Investigation of c-KIT and Ki67 expression in normal, preneoplastic and neoplastic canine prostate.

PubMed

Fonseca-Alves, Carlos Eduardo; Kobayashi, Priscilla Emiko; Palmieri, Chiara; Laufer-Amorim, Renée

2017-12-06

c-KIT expression has been related to bone metastasis in human prostate cancer, but whether c-KIT expression can be similarly classified in canine prostatic tissue is unknown. This study assessed c-KIT and Ki67 expression in canine prostate cancer (PC). c-KIT gene and protein expression and Ki67 expression were evaluated in forty-four canine prostatic tissues by immunohistochemistry, RT-qPCR and western blot. Additionally, we have investigated c-KIT protein expression by immunoblotting in two primary canine prostate cancer cell lines. Eleven normal prostates, 12 proliferative inflammatory atrophy (PIA) prostates, 18 PC, 3 metastatic lesions and two prostate cancer cell cultures (PC1 and PC2) were analysed. The prostatic tissue exhibited varying degrees of membranous, cytoplasmic or membranous/cytoplasmic c-KIT staining. Four normal prostates, 4 PIA and 5 prostatic carcinomas showed positive c-KIT expression. No c-KIT immunoexpression was observed in metastases. Canine prostate cancer and PIA samples contained a higher number of Ki67-positive cells compared to normal samples. The median relative quantification (RQ) for c-KIT expression in normal, PIA and prostate cancer and metastatic samples were 0.6 (0.1-2.5), 0.7 (0.09-2.1), 0.7 (0.09-5.1) and 0.1 (0.07-0.6), respectively. A positive correlation between the number of Ki67-positive cells and c-KIT transcript levels was observed in prostate cancer samples. In the cell line, PC1 was negative for c-KIT protein expression, while PC2 was weakly positive. The present study identified a strong correlation between c-KIT expression and proliferative index, suggesting that c-KIT may influence cell proliferation. Therefore, c-KIT heterogeneous protein expression among the samples (five positive and thirteen negative prostate cancer samples) indicates a personalized approach for canine prostate cancer.

A Multimedia Interactive Education System for Prostate Cancer Patients: Development and Preliminary Evaluation

PubMed Central

Butz, Brian P

2004-01-01

Background A cancer diagnosis is highly distressing. Yet, to make informed treatment choices patients have to learn complicated disease and treatment information that is often fraught with medical and statistical terminology. Thus, patients need accurate and easy-to-understand information. Objective To introduce the development and preliminary evaluation through focus groups of a novel highly-interactive multimedia-education software program for patients diagnosed with localized prostate cancer. Methods The prostate interactive education system uses the metaphor of rooms in a virtual health center (ie, reception area, a library, physician offices, group meeting room) to organize information. Text information contained in the library is tailored to a person's information-seeking preference (ie, high versus low information seeker). We conducted a preliminary evaluation through 5 separate focus groups with prostate cancer survivors (N = 18) and their spouses (N = 15). Results Focus group results point to the timeliness and high acceptability of the software among the target audience. Results also underscore the importance of a guide or tutor who assists in navigating the program and who responds to queries to facilitate information retrieval. Conclusions Focus groups have established the validity of our approach and point to new directions to further enhance the user interface. PMID:15111269

Radiation-induced complications in prostate cancer patients treated with radiotherapy

NASA Astrophysics Data System (ADS)

Azuddin, A. Yusof; Rahman, I. Abdul; Siah, N. J.; Mohamed, F.; Saadc, M.; Ismail, F.

2014-09-01

The purpose of the study is to determine the relationship between radiation-induced complications with dosimetric and radiobiological parameters for prostate cancer patients that underwent the conformal radiotherapy treatment. 17 prostate cancer patients that have been treated with conformal radiotherapy were retrospectively analysed. The dosimetric data was retrieved in the form of dose-volume histogram (DVH) from Radiotherapy Treatment Planning System. The DVH was utilised to derived Normal Tissue Complication Probability (NTCP) in radiobiological data. Follow-up data from medical records were used to grade the occurrence of acute gastrointestinal (GI) and genitourinary (GU) complications using Radiation Therapy Oncology Group (RTOG) scoring system. The chi-square test was used to determine the relationship between radiation-induced complication with dosimetric and radiobiological parameters. 8 (47%) and 7 (41%) patients were having acute GI and GU complications respectively. The acute GI complication can be associated with V60rectum, rectal mean dose and NTCPrectum with p-value of 0.016, 0.038 and 0.049 respectively. There are no significant relationships of acute GU complication with dosimetric and radiobiological variables. Further study can be done by increase the sample size and follow up duration for deeper understanding of the factors that effecting the GU and GI complication in prostate cancer radiotherapy.

EphA2 enhances the proliferation and invasion ability of LNCaP prostate cancer cells.

PubMed

Chen, Peijie; Huang, Yan; Zhang, Bo; Wang, Qiuquan; Bai, Peiming

2014-07-01

EphA2 is persistently overexpressed and functionally changed in numerous human cancers. However, to the best of our knowledge, the role that EphA2 plays in prostate cancer is not entirely clear. To investigate the roles of EphA2 in the development and progression of prostate cancer, the present study initially evaluated the roles of the EphA2 protein in LNCaP prostate cancer cells using recombinant plasmid, western blot analysis, flow cytometry, Matrigel invasion chamber and the cell counting kit-8 assay. An immunohistochemistry assay was also conducted to observe the effects of EphA2 in prostate cancer tissues. The results demonstrated that the LNCaP human prostate cancer cells that were transfected with pcDNA3.1(+) plasmid-mediated pcDNA3.1(+)-EphA2, markedly enhanced the cell growth and invasion in vitro . Additionally, EphA2 was overexpressed in prostate cancer specimens and the expression of EphA2 was significantly associated with Gleason grade, total prostate-specific antigen, advanced clinical stage and lymph node metastasis. Collectively, these results demonstrate that EphA2 is involved in malignant cell behavior and is a potential therapeutic target in human prostate cancer.

Diet and prostate cancer - a holistic approach to management.

PubMed

Cheetham, Philippa J; Katz, Aaron E

2011-10-01

There is now increasing evidence from epidemiologic surveys and from laboratory, intervention, and case-control studies that diet and lifestyle plays a crucial role in prostate cancer biology and tumorigenesis. This applies to both the development and progression of prostate cancer, although in many cases the specific initiating factors in the diet are poorly understood. Conversely, many nutrients and herbs also show significant promise in helping to treat prostate cancer by slowing progression and reducing recurrence, ultimately reducing the risk of morbidity and mortality from the disease. Furthermore for all grades of prostate cancer, nutritional interventions complement conventional treatment to improve response and quality of life. Slowing or even reversing the progression of, high-grade prostate intraepithelial neoplasia [HGPIN]). with chemo-preventative agents could be the best primary defense against prostate cancer, preventing it from occurring in the first place. The information given in this review about prostate cancer chemoprevention summarizes the key evidence for the role of different dietary components and their effect on prostate cancer prevention and progression. Most nutritional chemoprevention agents also have the added benefit of being beneficial for the cardiovascular system, bone health and for the prevention of other cancers.

Prostate cancer, benign prostatic hyperplasia and physical activity in Shanghai, China.

PubMed

Lacey, J V; Deng, J; Dosemeci, M; Gao, Y T; Mostofi, F K; Sesterhenn, I A; Xie, T; Hsing, A W

2001-04-01

Studies suggest that increased levels of physical activity might decrease the risk of prostate cancer. We ascertained lifetime measures of activity in a population-based case-control study of prostate cancer in Shanghai, China to investigate physical activity in a population where the incidence of prostate cancer is low but rising. In all, 238 men with prostate cancer, diagnosed 1993-1995, were identified through a rapid reporting system. A second group of 206 men with benign prostatic hyperplasia (BPH) was matched to prostate cancer cases, and 471 age-matched and population-based controls were identified from urban Shanghai. Through personal interviews, we ascertained all daily, occupational, and recreational activities at ages 20-29, ages 40-49, and in 1988 to generate hours spent sleeping, sitting, in moderate activity, and in vigorous activity. Time spent per week in different activities was converted to metabolic equivalents (MET-h) and energy expended. Time spent in, MET-h of, and energy expended in physical activities were not consistently related to either prostate cancer or BPH when compared to controls. Few men reported regular vigorous activity. Occupational activity, based on an energy expenditure index using job titles, was suggestively associated with a decreased risk of BPH, but not associated with prostate cancer. Associations did not vary according to age or stage of prostate cancer at diagnosis. Our results, based on regular physical activity, occupational activity, hours in activities, MET-h, and energy expended, did not support a protective role of physical activity in prostate cancer or BPH for men in a low-risk population.

PCOTH, a novel gene overexpressed in prostate cancers, promotes prostate cancer cell growth through phosphorylation of oncoprotein TAF-Ibeta/SET.

PubMed

Anazawa, Yoshio; Nakagawa, Hidewaki; Furihara, Mutsuo; Ashida, Shingo; Tamura, Kenji; Yoshioka, Hiroki; Shuin, Taro; Fujioka, Tomoaki; Katagiri, Toyomasa; Nakamura, Yusuke

2005-06-01

Through genome-wide cDNA microarray analysis coupled with microdissection of prostate cancer cells, we identified a novel gene, prostate collagen triple helix (PCOTH), showing overexpression in prostate cancer cells and its precursor cells, prostatic intraepithelial neoplasia (PIN). Immunohistochemical analysis using polyclonal anti-PCOTH antibody confirmed elevated expression of PCOTH, a 100-amino-acid protein containing collagen triple-helix repeats, in prostate cancer cells and PINs. Knocking down PCOTH expression by small interfering RNA (siRNA) resulted in drastic attenuation of prostate cancer cell growth, and concordantly, LNCaP derivative cells that were designed to constitutively express exogenous PCOTH showed higher growth rate than LNCaP cells transfected with mock vector, suggesting the growth-promoting effect of PCOTH on prostate cancer cell. To investigate the biological mechanisms of this growth-promoting effect, we applied two-dimensional differential gel electrophoresis (2D-DIGE) to analyze the phospho-protein fractions in LNCaP cells transfected with PCOTH. We found that the phosphorylation level of oncoprotein TAF-Ibeta/SET was significantly elevated in LNCaP cells transfected with PCOTH than control LNCaP cells, and these findings were confirmed by Western blotting and in-gel kinase assay. Furthermore, knockdown of endogenous TAF-Ibeta expression by siRNA also attenuated viability of prostate cancer cells as well. These findings suggest that PCOTH is involved in growth and survival of prostate cancer cells thorough, in parts, the TAF-Ibeta pathway, and that this molecule should be a promising target for development of new therapeutic strategies for prostate cancers.

Differential expression of miR-34b and androgen receptor pathway regulate prostate cancer aggressiveness between African-Americans and Caucasians

PubMed Central

Kato, Taku; Yamamura, Soichiro; Tanaka, Yuichiro; Majid, Shahana; Saini, Sharanjot; Varahram, Shahryari; Kulkarni, Priyanka; Dasgupta, Pritha; Mitsui, Yozo; Sumida, Mitsuho; Tabatabai, Laura; Deng, Guoren; Kumar, Deepak; Dahiya, Rajvir

2017-01-01

African-Americans are diagnosed with more aggressive prostate cancers and have worse survival than Caucasians, however a comprehensive understanding of this health disparity remains unclear. To clarify the mechanisms leading to this disparity, we analyzed the potential involvement of miR-34b expression in African-Americans and Caucasians. miR-34b functions as a tumor suppressor and has a multi-functional role, through regulation of cell proliferation, cell cycle and apoptosis. We found that miR-34b expression is lower in human prostate cancer tissues from African-Americans compared to Caucasians. DNA hypermethylation of the miR-34b-3p promoter region showed significantly higher methylation in prostate cancer compared to normal samples. We then sequenced the promoter region of miR-34b-3p and found a chromosomal deletion in miR-34b in African-American prostate cancer cell line (MDA-PCA-2b) and not in Caucasian cell line (DU-145). We found that AR and ETV1 genes are differentially expressed in MDA-PCa-2b and DU-145 cells after overexpression of miR-34b. Direct interaction of miR-34b with the 3’ untranslated region of AR and ETV1 was validated by luciferase reporter assay. We found that miR-34b downregulation in African-Americans is inversely correlated with high AR levels that lead to increased cell proliferation. Overexpression of miR-34b in cell lines showed higher inhibition of cell proliferation, apoptosis and G1 arrest in the African-American cells (MDA-PCa-2b) compared to Caucasian cell line (DU-145). Taken together, our results show that differential expression of miR-34b and AR are associated with prostate cancer aggressiveness in African-Americans. PMID:28039468

Development and assessment of an evidence-based prostate cancer intervention programme for black men: the W.O.R.D. on prostate cancer video.

PubMed

Odedina, Folakemi; Oluwayemisi, Awoyemi O; Pressey, Shannon; Gaddy, Samuel; Egensteiner, Eva; Ojewale, Ezekiel O; Moline, Olivia Myra; Martin, Chloe Marie

2014-01-01

In spite of the numerous prostate cancer (CaP) intervention programmes that have been implemented to address the disparities experienced by black men, CaP prevention, risk reduction, and early detection behaviours remain low among black men. The lack of formal theoretical frameworks to guide the development and implementation of interventions has been recognised as one of the primary reasons for the failure of health interventions. Members of the Florida Prostate Cancer Health Disparity (CaPHD) group employed the Personal Model of Prostate Cancer Disparity (PIPCaD) model and the Health Communication Process Model to plan, implement, and evaluate an intervention programme, the 'Working through Outreach to Reduce Disparity (W.O.R.D. on Prostate Cancer)' video for black men. The location for the video was in a barbershop, a popular setting for the targeted group. The video starred CaP survivors, CaP advocates, a radio personality, and barbers. In addition, remarks were provided by a CaP scientist, a urologist, a CaP advocate, a former legislator, and a minister. The W.O.R.D. video was developed to assist black men in meeting the Healthy People 2020 goal for the United States of America. The efficacy of the W.O.R.D. video was successfully established among 143 black men in Florida. Exposure to the video was found to statistically increase CaP knowledge and intention to participate in CaP screening. Furthermore, exposure to the video statistically decreased participants' perception of the number of factors contributing to decision, uncertainty about CaP screening. Participants were highly satisfied with the video content and rated the quality of the video to be very good. Participants also rated the video as credible, informative, useful, relevant, understandable, not too time consuming, clear, and interesting.

Development and assessment of an evidence-based prostate cancer intervention programme for black men: the W.O.R.D. on prostate cancer video

PubMed Central

Odedina, Folakemi; Oluwayemisi, Awoyemi O; Pressey, Shannon; Gaddy, Samuel; Egensteiner, Eva; Ojewale, Ezekiel O; Moline, Olivia Myra; Martin, Chloe Marie

2014-01-01

In spite of the numerous prostate cancer (CaP) intervention programmes that have been implemented to address the disparities experienced by black men, CaP prevention, risk reduction, and early detection behaviours remain low among black men. The lack of formal theoretical frameworks to guide the development and implementation of interventions has been recognised as one of the primary reasons for the failure of health interventions. Members of the Florida Prostate Cancer Health Disparity (CaPHD) group employed the Personal Model of Prostate Cancer Disparity (PIPCaD) model and the Health Communication Process Model to plan, implement, and evaluate an intervention programme, the ‘Working through Outreach to Reduce Disparity (W.O.R.D. on Prostate Cancer)’ video for black men. The location for the video was in a barbershop, a popular setting for the targeted group. The video starred CaP survivors, CaP advocates, a radio personality, and barbers. In addition, remarks were provided by a CaP scientist, a urologist, a CaP advocate, a former legislator, and a minister. The W.O.R.D. video was developed to assist black men in meeting the Healthy People 2020 goal for the United States of America. The efficacy of the W.O.R.D. video was successfully established among 143 black men in Florida. Exposure to the video was found to statistically increase CaP knowledge and intention to participate in CaP screening. Furthermore, exposure to the video statistically decreased participants’ perception of the number of factors contributing to decision, uncertainty about CaP screening. Participants were highly satisfied with the video content and rated the quality of the video to be very good. Participants also rated the video as credible, informative, useful, relevant, understandable, not too time consuming, clear, and interesting. PMID:25228916

FOXP3+ regulatory T cells in normal prostate tissue, postatrophic hyperplasia, prostatic intraepithelial neoplasia, and tumor histological lesions in men with and without prostate cancer

PubMed Central

Andren, Ove; Ohlson, Anna‐Lena; Carlsson, Jessica; Andersson, Swen‐Olof; Giunchi, Francesca; Rider, Jennifer R.; Fiorentino, Michelangelo

2017-01-01

Background The tumor promoting or counteracting effects of the immune response to cancer development are thought to be mediated to some extent by the infiltration of regulatory T cells (Tregs). In the present study we evaluated the prevalence of Treg populations in stromal and epithelial compartments of normal, post atrophic hyperplasia (PAH), prostatic intraepithelial neoplasia (PIN), and tumor lesions in men with and without prostate cancer. Methods Study subjects were 102 men consecutively diagnosed with localized prostate cancer undergoing radical prostatectomy and 38 men diagnosed with bladder cancer undergoing cystoprostatectomy without prostate cancer at the pathological examination. Whole mount sections from all patients were evaluated for the epithelial and stromal expression of CD4+ Tregs and CD8+ Tregs in normal, PAH, PIN, and tumor lesions. A Friedmańs test was used to investigate differences in the mean number of Tregs across histological lesions. Logistic regression was used to estimate crude and adjusted odds ratios (OR) for prostate cancer for each histological area. Results In men with prostate cancer, similarly high numbers of stromal CD4+ Tregs were identified in PAH and tumor, but CD4+ Tregs were less common in PIN. Greater numbers of epithelial CD4+ Tregs in normal prostatic tissue were positively associated with both Gleason score and pT‐stage. We observed a fourfold increased risk of prostate cancer in men with epithelial CD4+ Tregs in the normal prostatic tissue counterpart. Conclusions Our results may suggest a possible pathway through which PAH develops directly into prostate cancer in the presence of CD4+ Tregs and indicate that transformation of the anti‐tumor immune response may be initiated even before the primary tumor is established. PMID:29105795

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.

Synchronous Detection of Male Breast Cancer and Prostatic Cancer in a Patient With Suspected Prostatic Carcinoma on 68Ga-PSMA PET/CT Imaging.

PubMed

Kumar, Rajender; Mittal, Bhagwant Rai; Bhattacharya, Anish; Singh, Harmandeep; Singh, Shrawan Kumar

2018-06-01

The male breast cancer is very less common as compared with the female breast cancer. We report a case of 64-year-old man who presented with the history of lower urinary tract symptoms. The digital rectal examination revealed hard and nodular prostate, and serum prostate-specific antigen level was 23.4 ng/mL. Ga-labeled prostate-specific membrane antigen PET/CT revealed prostate-specific membrane antigen-expressing lesions in the prostate, axillary tail of the right breast, and axillary lymph nodes. Histology from prostate revealed prostate carcinoma, whereas fine-needle aspiration from the breast revealed invasive ductal carcinoma of the breast.

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.

Role of monocyte-lineage cells in prostate cancer cell invasion and tissue factor expression.

PubMed

Lindholm, Paul F; Lu, Yi; Adley, Brian P; Vladislav, Tudor; Jovanovic, Borko; Sivapurapu, Neela; Yang, Ximing J; Kajdacsy-Balla, André

2010-11-01

Tissue factor (TF) is a cell surface glycoprotein intricately related to blood coagulation and inflammation. This study was performed to investigate the role of monocyte-lineage cells in prostate cancer cell TF expression and cell invasion. Prostate cancer cell invasion was tested with and without added peripheral blood monocytes or human monocyte-lineage cell lines. TF neutralizing antibodies were used to determine the TF requirement for prostate cancer cell invasion activity. Immunohistochemistry was performed to identify prostate tissue CD68 positive monocyte-derived cells and prostate epithelial TF expression. Co-culture of PC-3, DU145, and LNCaP cells with isolated human monocytes significantly stimulated prostate cancer cell invasion activity. TF expression was greater in highly invasive prostate cancer cells and was induced in PC-3, DU145, and LNCaP cells by co-culture with U-937 cells, but not with THP-1 cells. TF neutralizing antibodies inhibited PC-3 cell invasion in co-cultures with monocyte-lineage U-937 or THP-1 cells. Prostate cancer tissues contained more CD68 positive cells in the stroma and epithelium (145 ± 53/mm(2)) than benign prostate (108 ± 31/mm(2)). Samples from advanced stage prostate cancer tended to contain more CD68 positive cells when compared with lower stage lesions. Prostatic adenocarcinoma demonstrated significantly increased TF expression compared with benign prostatic epithelium. This study shows that co-culture with monocyte-lineage cells induced prostate cancer cell invasion activity. PC-3 invasion and TF expression was induced in co-culture with U-937 cells and partially inhibited with TF neutralizing antibodies.

Effect of Diabetes and Obesity on Disparities in Prostate Cancer Outcomes

DTIC Science & Technology

2016-10-01

AWARD NUMBER: W81XWH-14-1-0503 TITLE: Effect of Diabetes and Obesity on Disparities in Prostate Cancer Outcomes PRINCIPAL INVESTIGATOR: Bettina F...Effect of Diabetes and Obesity on Disparities in Prostate Cancer Outcomes 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0503 5c. PROGRAM ELEMENT...prostate cancer related death by identifying potential modifiable factors. 15. SUBJECT TERMS Prostate cancer, disparities, VHA and VACCR data, obesity

Development of Assays for Detecting Significant Prostate Cancer Based on Molecular Alterations Associated with Cancer in Non-Neoplastic Prostate Tissue

DTIC Science & Technology

2016-12-01

Award Number: W81XWH-11-1-0744 TITLE: Development of Assays for Detecting Significant Prostate Cancer Based on Molecular Alterations Associated...Significant Prostate Cancer Based on Molecular Alterations Associated with Cancer in Non- Neoplastic Prostate Tissue 5b. GRANT NUMBER 10623678 5c...Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The goal of this project was to develop molecular models to

Height, selected genetic markers and prostate cancer risk: results from the PRACTICAL consortium.

PubMed

Lophatananon, Artitaya; Stewart-Brown, Sarah; Kote-Jarai, Zsofia; Olama, Ali Amin Al; Garcia, Sara Benlloch; Neal, David E; Hamdy, Freddie C; Donovan, Jenny L; Giles, Graham G; Fitzgerald, Liesel M; Southey, Melissa C; Pharoah, Paul; Pashayan, Nora; Gronberg, Henrik; Wiklund, Fredrik; Aly, Markus; Stanford, Janet L; Brenner, Hermann; Dieffenbach, Aida K; Arndt, Volker; Park, Jong Y; Lin, Hui-Yi; Sellers, Thomas; Slavov, Chavdar; Kaneva, Radka; Mitev, Vanio; Batra, Jyotsna; Spurdle, Amanda; Clements, Judith A; Easton, Douglas; Eeles, Rosalind A; Muir, Kenneth

2017-08-22

Evidence on height and prostate cancer risk is mixed, however, recent studies with large data sets support a possible role for its association with the risk of aggressive prostate cancer. We analysed data from the PRACTICAL consortium consisting of 6207 prostate cancer cases and 6016 controls and a subset of high grade cases (2480 cases). We explored height, polymorphisms in genes related to growth processes as main effects and their possible interactions. The results suggest that height is associated with high-grade prostate cancer risk. Men with height >180 cm are at a 22% increased risk as compared to men with height <173 cm (OR 1.22, 95% CI 1.01-1.48). Genetic variants in the growth pathway gene showed an association with prostate cancer risk. The aggregate scores of the selected variants identified a significantly increased risk of overall prostate cancer and high-grade prostate cancer by 13% and 15%, respectively, in the highest score group as compared to lowest score group. There was no evidence of gene-environment interaction between height and the selected candidate SNPs.Our findings suggest a role of height in high-grade prostate cancer. The effect of genetic variants in the genes related to growth is seen in all cases and high-grade prostate cancer. There is no interaction between these two exposures.

Coffee and tea consumption in relation to prostate cancer prognosis

PubMed Central

Geybels, Milan S.; Neuhouser, Marian L.; Wright, Jonathan L.; Stott-Miller, Marni; Stanford, Janet L.

2013-01-01

Background Bioactive compounds found in coffee and tea may delay the progression of prostate cancer. Methods We investigated associations of pre-diagnostic coffee and tea consumption with risk of prostate cancer recurrence/progression. Study participants were men diagnosed with prostate cancer in 2002–2005 in King County, Washington, USA. We assessed the usual pattern of coffee and tea consumption two years before diagnosis date. Prostate cancer outcome events were identified using a detailed follow-up survey. Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results The analysis of coffee intake in relation to prostate cancer recurrence/progression included 630 patients with a median follow-up of 6.4 years, during which 140 prostate cancer recurrence/progression events were recorded. Approximately 61% of patients consumed at least one cup of coffee per day. Coffee consumption was associated with a reduced risk of prostate cancer recurrence/progression; the adjusted HR for ≥4 cups/day versus ≤1 cup/week was 0.41 (95% CI: 0.20, 0.81; P for trend = 0.01). Approximately 14% of patients consumed one or more cups of tea per day, and tea consumption was unrelated to prostate cancer recurrence/progression. Conclusion Results indicate that pre-diagnostic coffee consumption is associated with a lower risk of prostate cancer recurrence/progression. This finding will require replication in larger studies. PMID:23907772

Association of genetic and non-genetic risk factors with the development of prostate cancer in Malaysian men.

PubMed

Munretnam, Khamsigan; Alex, Livy; Ramzi, Nurul Hanis; Chahil, Jagdish Kaur; Kavitha, I S; Hashim, Nikman Adli Nor; Lye, Say Hean; Velapasamy, Sharmila; Ler, Lian Wee

2014-01-01

There is growing global interest to stratify men into different levels of risk to developing prostate cancer, thus it is important to identify common genetic variants that confer the risk. Although many studies have identified more than a dozen common genetic variants which are highly associated with prostate cancer, none have been done in Malaysian population. To determine the association of such variants in Malaysian men with prostate cancer, we evaluated a panel of 768 SNPs found previously associated with various cancers which also included the prostate specific SNPs in a population based case control study (51 case subjects with prostate cancer and 51 control subjects) in Malaysian men of Malay, Chinese and Indian ethnicity. We identified 21 SNPs significantly associated with prostate cancer. Among these, 12 SNPs were strongly associated with increased risk of prostate cancer while remaining nine SNPs were associated with reduced risk. However, data analysis based on ethnic stratification led to only five SNPs in Malays and 3 SNPs in Chinese which remained significant. This could be due to small sample size in each ethnic group. Significant non-genetic risk factors were also identified for their association with prostate cancer. Our study is the first to investigate the involvement of multiple variants towards susceptibility for PC in Malaysian men using genotyping approach. Identified SNPs and non-genetic risk factors have a significant association with prostate cancer.

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.

TOP2A and EZH2 Provide Early Detection of an Aggressive Prostate Cancer Subgroup.

PubMed

Labbé, David P; Sweeney, Christopher J; Brown, Myles; Galbo, Phillip; Rosario, Spencer; Wadosky, Kristine M; Ku, Sheng-Yu; Sjöström, Martin; Alshalalfa, Mohammed; Erho, Nicholas; Davicioni, Elai; Karnes, R Jeffrey; Schaeffer, Edward M; Jenkins, Robert B; Den, Robert B; Ross, Ashley E; Bowden, Michaela; Huang, Ying; Gray, Kathryn P; Feng, Felix Y; Spratt, Daniel E; Goodrich, David W; Eng, Kevin H; Ellis, Leigh

2017-11-15

Purpose: Current clinical parameters do not stratify indolent from aggressive prostate cancer. Aggressive prostate cancer, defined by the progression from localized disease to metastasis, is responsible for the majority of prostate cancer-associated mortality. Recent gene expression profiling has proven successful in predicting the outcome of prostate cancer patients; however, they have yet to provide targeted therapy approaches that could inhibit a patient's progression to metastatic disease. Experimental Design: We have interrogated a total of seven primary prostate cancer cohorts ( n = 1,900), two metastatic castration-resistant prostate cancer datasets ( n = 293), and one prospective cohort ( n = 1,385) to assess the impact of TOP2A and EZH2 expression on prostate cancer cellular program and patient outcomes. We also performed IHC staining for TOP2A and EZH2 in a cohort of primary prostate cancer patients ( n = 89) with known outcome. Finally, we explored the therapeutic potential of a combination therapy targeting both TOP2A and EZH2 using novel prostate cancer-derived murine cell lines. Results: We demonstrate by genome-wide analysis of independent primary and metastatic prostate cancer datasets that concurrent TOP2A and EZH2 mRNA and protein upregulation selected for a subgroup of primary and metastatic patients with more aggressive disease and notable overlap of genes involved in mitotic regulation. Importantly, TOP2A and EZH2 in prostate cancer cells act as key driving oncogenes, a fact highlighted by sensitivity to combination-targeted therapy. Conclusions: Overall, our data support further assessment of TOP2A and EZH2 as biomarkers for early identification of patients with increased metastatic potential that may benefit from adjuvant or neoadjuvant targeted therapy approaches. Clin Cancer Res; 23(22); 7072-83. ©2017 AACR . ©2017 American Association for Cancer Research.

Differential Gene Expression in Benign Prostate Epithelium of Men with and without Prostate Cancer: Evidence for a Prostate Cancer Field Effect

PubMed Central

Risk, Michael C; Knudsen, Beatrice S; Coleman, Ilsa; Dumpit, Ruth F; Kristal, Alan R; LeMeur, Nolwenn; Gentleman, Robert C; True, Lawrence D; Nelson, Peter S; Lin, Daniel W

2010-01-01

Background Several malignancies are known to exhibit a “field-effect” whereby regions beyond tumor boundaries harbor histological or molecular changes that are associated with cancer. We sought to determine if histologically benign prostate epithelium collected from men with prostate cancer exhibits features indicative of pre-malignancy or field effect. Methods Prostate needle biopsies from 15 men with high grade(Gleason 8–10) prostate cancer and 15 age- and BMI-matched controls were identified from a biospecimen repository. Benign epithelia from each patient were isolated by laser capture microdissection. RNA was isolated, amplified, and used for microarray hybridization. Quantitative PCR(qPCR) was used to determine the expression of specific genes of interest. Alterations in protein expression were analyzed through immunohistochemistry. Results Overall patterns of gene expression in microdissected benign-associated benign epithelium (BABE) and cancer-associated benign epithelium (CABE) were similar. Two genes previously associated with prostate cancer, PSMA and SSTR1, were significantly upregulated in the CABE group(FDR <1%). Expression of other prostate cancer-associated genes, including ERG, HOXC4, HOXC5 and MME, were also increased in CABE by qRT-PCR, although other genes commonly altered in prostate cancer were not different between the BABE and CABE samples. The expression of MME and PSMA proteins on IHC coincided with their mRNA alterations. Conclusion Gene expression profiles between benign epithelia of patients with and without prostate cancer are very similar. However, these tissues exhibit differences in the expression levels of several genes previously associated with prostate cancer development or progression. These differences may comprise a field effect and represent early events in carcinogenesis. PMID:20935156

Overexpression of HepaCAM inhibits cell viability and motility through suppressing nucleus translocation of androgen receptor and ERK signaling in prostate cancer.

PubMed

Song, Xuedong; Wang, Yin; Du, Hongfei; Fan, Yanru; Yang, Xue; Wang, Xiaorong; Wu, Xiaohou; Luo, Chunli

2014-07-01

HepaCAM is suppressed in a variety of human cancers, and involved in cell adhesion, growth, migration, invasion, and survival. However, the expression and function of HepaCAM in prostate cancer are still unknown. HepaCAM expression has been detected by RT-PCR, Western blotting and immunohistochemistry staining in prostate cell lines RWPE-1, LNCap, DU145, PC3, and in 75 human prostate tissue specimens, respectively. Meanwhile, the cell proliferation ability was detected by WST-8 assay. The role of HepaCAM in prostate cancer cell migration and invasion was examined by wound healing and transwell assay. And flow cytometry was used to observe the apoptosis of prostate cancer cells. Then we detected changes of Androgen Receptor translocation and ERK signaling using immunofluorescence staining and western blot after overexpression of HepaCAM. The HepaCAM expression was significantly down-regulated in prostate cancer tissues and undetected in prostate cancer cells. However, the low HepaCAM expression was not statistically associated with clinicopathological characteristics of prostate cancer. Overexpression of HepaCAM in prostate cancer cells decreased the cell proliferation, migration and invasion, and induced the cell apoptosis. Meanwhile, HepaCAM prevented the androgen receptor translocation from the cytoplasm to the nucleus and down-regulated the MAPK/ERK signaling. Our results suggested that HepaCAM acted as a tumor suppressor in prostate cancer. HepaCAM inhibited cell viability and motility which might be through suppressing the nuclear translocation of Androgen Receptor and down-regulating the ERK signaling. Therefore, it was indicated that HepaCAM may be a potential therapeutic target for prostate cancer. © 2014 Wiley Periodicals, Inc.

Exploring prostate cancer literacy and family cancer awareness in college students: getting ahead of the curve in cancer education.

PubMed

Campbell, Lisa C; McClain, Jasmyne

2013-12-01

Cancer literacy and family cancer experiences have not been widely researched from the perspective of young adults. This study examined health literacy related to prostate cancer and family cancer awareness among a sample of 146 male and female college students. Results supported conventional wisdom that males would be more knowledgeable about the anatomical location of the prostate as compared to females. More notably, across the sample participants had limited knowledge of comprehensive prostate cancer screening but were generally aware of the prostate specific antigen blood test, as well as age and diet as risk factors for prostate cancer. Emerging associations between sexual health history and prostate cancer risk were not widely known by the sample as a whole and perceived availability of prostate health education in college was low. Finally, gender differences in family communication about cancer and racial differences in the number of family members with cancer were observed, which could have implications for perpetuating existing gender and racial gaps in health literacy and cancer awareness. A lifespan approach to cancer education research is suggested to identify ways to promote lifelong learning about cancer, promote prevention behaviors and informed screening in young adulthood, and beyond and better prepare adults to face a family or personal cancer diagnosis should that occur in the future.

Cabazitaxel for the treatment of prostate cancer.

PubMed

Michielsen, Dirk P J; Braeckman, Johan G; Denis, Louis

2011-04-01

Prostate cancer is a frequently diagnosed male cancer. In men presenting locally advanced or metastatic disease, the mainstay of treatment is hormonal suppression. Despite the castrate levels of testosterone, with time, prostate cancer gradually evolves into a castration-refractory state. Chemotherapeutic agents are able to influence the natural history of metastatic castration-resistant prostate cancer. Docetaxel is a clinically relevant, FDA-approved taxane. Today, it is the first-line chemotherapeutic agent in castration-refractory prostate cancer (CRPC). There is no standard second-line chemotherapeutic regimen. This review provides information on the efficacy of cabazitaxel as a second-line treatment for CRPC. The medline database was searched for clinical trials on chemotherapeutical treatment options of castration-resistant prostate cancer. All available data on the efficacy of cabazitaxel are summarized. New treatment strategies for castration-resistant prostate cancer should primarily focus on quality of life. In this view, vaccination therapy seems promising because of the acceptable level of toxicity. However, more research is needed to prove their efficacy in the treatment of castration-resistant prostate cancer. Cabazitaxel seems to be a promising second-line therapy in CRPC.

Vasectomy and prostate cancer risk: a historical synopsis of undulating false causality.

PubMed

Nutt, Max; Reed, Zachary; Köhler, Tobias S

2016-01-01

The potential influence of vasectomy being a risk factor for the development of prostate cancer is not a new concept, with more than 30 publications addressing the topic. Given the global frequency of vasectomy and the prevalence of prostate cancer, this subject justifiably deserves scrutiny. Several articles have claimed that vasectomy puts men at risk for future development of prostate cancer. We explore articles that have shown the contrary (no link), explore the studies' strengths and weaknesses, describe possible prostate cancer pathophysiologic mechanisms, and apply Bradford Hill criteria to help discern correlation with causation. The risk and interest of association of prostate cancer with vasectomy has waxed and waned over the last three decades. Based on our review, vasectomy remains a safe form of sterilization and does not increase prostate cancer risk.

Molecular Characterization of Indolent Prostate Cancer

DTIC Science & Technology

2016-12-01

prostate - specific antigen (PSA) test, and treated aggressively following diagnosis, leading to the contemporary problem of prostate cancer over-diagnosis... specific purpose of comparing low- risk and high-risk prostate cancer. Figure 3 shows the mapping rates for exon, intron, and inter-genic sequences. The...FFPE specimens, for the specific comparison of low-risk and high-risk prostate cancer. 5. Identified sufficient number of biopsy cases and sections

Combination therapy for biochemically recurrent prostate cancer tested in new trial | Center for Cancer Research

Cancer.gov

Prostate-specific antigen (PSA) is an enzyme released by the prostate gland and is found in abnormally high concentrations in the blood of men with prostate cancer. “Biochemical recurrence” is when PSA levels continue to rise after initial treatment for prostate cancer, such as surgery or radiation. Marijo Bilusic, M.D., of the Genitourinary Malignancies Branch is leading the

Intraductal Carcinoma of the Prostate on Diagnostic Needle Biopsy Predicts Prostate Cancer Mortality: A Population-Based Study.

PubMed

Saeter, Thorstein; Vlatkovic, Ljiljana; Waaler, Gudmund; Servoll, Einar; Nesland, Jahn M; Axcrona, Karol; Axcrona, Ulrika

2017-06-01

Intraductal carcinoma of the prostate (IDC-P) is a distinct histopathologic feature associated with high-grade, advanced prostate cancer. Although studies have shown that IDC-P is a predictor of progression following surgical or radiation treatment for prostate cancer, there are sparse data regarding IDC-P on diagnostic needle biopsy as a prognosticator of prostate cancer mortality. This was a population-based study of all prostate cancer patients diagnosed using needle biopsy and without evidence of systemic disease between 1991 and 1999 within a defined geographic region of Norway. Patients were identified by cross-referencing the Norwegian Cancer Registry. Of 318 eligible patients, 283 had biopsy specimens available for central pathology review. Clinical data were obtained from medical charts. We examined whether IDC-P on diagnostic needle biopsy was associated with adverse clinicopathological features and prostate cancer mortality. Patients with IDC-P on diagnostic needle biopsy had a more advanced stage and a higher Gleason score compared to patients without IDC-P. IDC-P was also associated with an intensively reactive stroma. The 10-year prostate cancer-specific survival was 69% for patients with IDC-P on diagnostic needle biopsy and 89% for patients without IDC-P (Log rank P-value < 0.005). The presence of IDC-P on diagnostic needle biopsy remained an independent predictor of prostate cancer mortality after adjustments for clinical prognostic factors and treatment. After adjustment for the newly implemented Grade Group system of prostate cancer, IDC-P showed a strong tendency toward statistical significance. However, IDC-P did not remain a statistically significant predictor in the multivariable analysis. IDC-P on diagnostic needle biopsy is an indicator of prostate cancer with a high risk of mortality. Accordingly, a diagnosis of IDC-P on needle biopsy should be reported and considered a feature of high-risk prostate cancer. Moreover, the association between IDC-P and reactive stroma provides evidence in support of the idea that stromal factors facilitate carcinoma invasion to the prostatic acini and ducts. Prostate 77:859-865, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

miR-128 modulates chemosensitivity and invasion of prostate cancer cells through targeting ZEB1.

PubMed

Sun, Xianglun; Li, Youkong; Yu, Jie; Pei, Hong; Luo, Pengcheng; Zhang, Jie

2015-05-01

Recent reports strongly suggest the profound role of miRNAs in cancer therapeutic response and progression, including invasion and metastasis. The sensitivity to therapy and invasion is the major obstacle for successful treatment in prostate cancer. We aimed to investigate the regulative effect of miR-128/zinc-finger E-box-binding homeobox 1 axis on prostate cancer cell chemosensitivity and invasion. The miR-128 expression pattern of prostate cancer cell lines and tissues was detected by real-time reverse transcriptase-polymerase chain reaction, while the mRNA and protein expression levels of zinc-finger E-box-binding homeobox 1 were measured by real-time reverse transcriptase-polymerase chain reaction and western blot assay, respectively. Dual-luciferase reporter gene assay was used to find the direct target of miR-128. Furthermore, prostate cancer cells were treated with miR-128 mimic or zinc-finger E-box-binding homeobox 1-siRNA, and then the cells' chemosensitivity and invasion were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and transwell assay, respectively. We found miR-128 expression obviously decreased in prostate cancer tissues compared with paired normal tissues. Restored miR-128 expression sensitized prostate cancer cells to cisplatin and inhibited the invasion. Furthermore, there was an inverse expression pattern between miR-128 and zinc-finger E-box-binding homeobox 1 in prostate cancer cells and tissues, and zinc-finger E-box-binding homeobox 1 was identified as a direct target of miR-128 in prostate cancer. Knockdown of zinc-finger E-box-binding homeobox 1 expression efficiently sensitized prostate cancer cells to cisplatin and inhibited the invasion. However, ectopic zinc-finger E-box-binding homeobox 1 expression impaired the effects of miR-128 on chemosensitivity and invasion in prostate cancer cells. miR-128 functions as a potential cancer suppressor in prostate cancer progression and rational therapeutic strategies for prostate cancer would be developed based on miR-128/zinc-finger E-box-binding homeobox 1 axis. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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.

Alzheimer's disease is associated with prostate cancer: a population-based study.

PubMed

Lin, Herng-Ching; Kao, Li-Ting; Chung, Shiu-Dong; Huang, Chung-Chien; Shia, Ben-Chang; Huang, Chao-Yuan

2018-01-26

Alzheimer's disease and cancer are increasingly prevalent with advancing age. However, the association between Alzheimer's disease and prostate cancer remains unclear. The aim of this study was to examine the relationship between prior Alzheimer's disease and subsequent prostate cancer using a population-based dataset in Taiwan. Data for this study were sourced from the Taiwan Longitudinal Health Insurance Database 2005. This case-control study included 2101 prostate cancer patients as cases and 6303 matched controls. We used conditional logistic regression analyses to calculate the odds ratio (OR) and corresponding 95% confidence interval (CI) for Alzheimer's disease between prostate cancer patients and controls. We found that of the 8404 sampled patients, 128 (1.5%) had been diagnosed with Alzheimer's disease prior to the index date. A Chi-squared test showed that there was a significant difference in the prevalences of prior Alzheimer's disease between prostate cancer patients and controls (2.1% vs. 1.3%, p < 0.001). The conditional logistic regression analysis showed that the OR of prior Alzheimer's disease for prostate cancer patients was 1.53 (95% CI: 1.06∼2.21) compared to controls. Furthermore, the OR of prior Alzheimer's disease for prostate cancer patients was 1.52 (95% CI: 1.04∼2.22) compared to controls after adjusting for hypertension, diabetes, coronary heart disease, hyperlipidemia, obesity, prostatitis, gonorrhea or chlamydia infection, testitis or epididymitis, and alcohol abuse/alcohol dependency syndrome. This study revealed an association between prior Alzheimer's disease and prostate cancer. We suggest that clinicians be alert to the increased risk of prostate cancer when caring for elderly individuals with Alzheimer's disease.

Genome scan study of prostate cancer in Arabs: identification of three genomic regions with multiple prostate cancer susceptibility loci in Tunisians.

PubMed

Shan, Jingxuan; Al-Rumaihi, Khalid; Rabah, Danny; Al-Bozom, Issam; Kizhakayil, Dhanya; Farhat, Karim; Al-Said, Sami; Kfoury, Hala; Dsouza, Shoba P; Rowe, Jillian; Khalak, Hanif G; Jafri, Shahzad; Aigha, Idil I; Chouchane, Lotfi

2013-05-13

Large databases focused on genetic susceptibility to prostate cancer have been accumulated from population studies of different ancestries, including Europeans and African-Americans. Arab populations, however, have been only rarely studied. Using Affymetrix Genome-Wide Human SNP Array 6, we conducted a genome-wide association study (GWAS) in which 534,781 single nucleotide polymorphisms (SNPs) were genotyped in 221 Tunisians (90 prostate cancer patients and 131 age-matched healthy controls). TaqMan SNP Genotyping Assays on 11 prostate cancer associated SNPs were performed in a distinct cohort of 337 individuals from Arab ancestry living in Qatar and Saudi Arabia (155 prostate cancer patients and 182 age-matched controls). In-silico expression quantitative trait locus (eQTL) analysis along with mRNA quantification of nearby genes was performed to identify loci potentially cis-regulated by the identified SNPs. Three chromosomal regions, encompassing 14 SNPs, are significantly associated with prostate cancer risk in the Tunisian population (P = 1 × 10-4 to P = 1 × 10-5). In addition to SNPs located on chromosome 17q21, previously found associated with prostate cancer in Western populations, two novel chromosomal regions are revealed on chromosome 9p24 and 22q13. eQTL analysis and mRNA quantification indicate that the prostate cancer associated SNPs of chromosome 17 could enhance the expression of STAT5B gene. Our findings, identifying novel GWAS prostate cancer susceptibility loci, indicate that prostate cancer genetic risk factors could be ethnic specific.

A genetic study and meta-analysis of the genetic predisposition of prostate cancer in a Chinese population.

PubMed

Marzec, Jacek; Mao, Xueying; Li, Meiling; Wang, Meilin; Feng, Ninghan; Gou, Xin; Wang, Guomin; Sun, Zan; Xu, Jianfeng; Xu, Hua; Zhang, Xiaoping; Zhao, Shan-Chao; Ren, Guoping; Yu, Yongwei; Wu, Yudong; Wu, Ji; Xue, Yao; Zhou, Bo; Zhang, Yanling; Xu, Xingxing; Li, Jie; He, Weiyang; Benlloch, Sara; Ross-Adams, Helen; Chen, Li; Li, Jucong; Hong, Yingqia; Kote-Jarai, Zsofia; Cui, Xingang; Hou, Jianguo; Guo, Jianming; Xu, Lei; Yin, Changjun; Zhou, Yuanping; Neal, David E; Oliver, Tim; Cao, Guangwen; Zhang, Zhengdong; Easton, Douglas F; Chelala, Claude; Al Olama, Ali Amin; Eeles, Rosalind A; Zhang, Hongwei; Lu, Yong-Jie

2016-04-19

Prostate cancer predisposition has been extensively investigated in European populations, but there have been few studies of other ethnic groups. To investigate prostate cancer susceptibility in the under-investigated Chinese population, we performed single-nucleotide polymorphism (SNP) array analysis on a cohort of Chinese cases and controls and then meta-analysis with data from the existing Chinese prostate cancer genome-wide association study (GWAS). Genotyping 211,155 SNPs in 495 cases and 640 controls of Chinese ancestry identified several new suggestive Chinese prostate cancer predisposition loci. However, none of them reached genome-wide significance level either by meta-analysis or replication study. The meta-analysis with the Chinese GWAS data revealed that four 8q24 loci are the main contributors to Chinese prostate cancer risk and the risk alleles from three of them exist at much higher frequencies in Chinese than European populations. We also found that several predisposition loci reported in Western populations have different effect on Chinese men. Therefore, this first extensive single-nucleotide polymorphism study of Chinese prostate cancer in comparison with European population indicates that four loci on 8q24 contribute to a great risk of prostate cancer in a considerable large proportion of Chinese men. Based on those four loci, the top 10% of the population have six- or two-fold prostate cancer risk compared with men of the bottom 10% or median risk respectively, which may facilitate the design of prostate cancer genetic risk screening and prevention in Chinese men. These findings also provide additional insights into the etiology and pathogenesis of prostate cancer.

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.

East meets West: ethnic differences in prostate cancer epidemiology between East Asians and Caucasians

PubMed Central

Kimura, Tomomi

2012-01-01

Prostate cancer is the most prevalent cancer in males in Western countries. The reported incidence in Asia is much lower than that in African Americans and European Caucasians. Although the lack of systematic prostate cancer screening system in Asian countries explains part of the difference, this alone cannot fully explain the lower incidence in Asian immigrants in the United States and west-European countries compared to the black and non-Hispanic white in those countries, nor the somewhat better prognosis in Asian immigrants with prostate cancer in the United States. Soy food consumption, more popular in Asian populations, is associated with a 25% to 30% reduced risk of prostate cancer. Prostate-specific antigen (PSA) is the only established and routinely implemented clinical biomarker for prostate cancer detection and disease status. Other biomarkers, such as urinary prostate cancer antigen 3 RNA, may increase accuracy of prostate cancer screening compared to PSA alone. Several susceptible loci have been identified in genetic linkage analyses in populations of countries in the West, and approximately 30 genetic polymorphisms have been reported to modestly increase the prostate cancer risk in genome-wide association studies. Most of the identified polymorphisms are reproducible regardless of ethnicity. Somatic mutations in the genomes of prostate tumors have been repeatedly reported to include deletion and gain of the 8p and 8q chromosomal regions, respectively; epigenetic gene silencing of glutathione S-transferase Pi (GSTP1); as well as mutations in androgen receptor gene. However, the molecular mechanisms underlying carcinogenesis, aggressiveness, and prognosis of prostate cancer remain largely unknown. Gene-gene and/or gene-environment interactions still need to be learned. In this review, the differences in PSA screening practice, reported incidence and prognosis of prostate cancer, and genetic factors between the populations in East and West factors are discussed. PMID:22085526

Sequence variants of Toll-like receptor 4 and susceptibility to prostate cancer.

PubMed

Chen, Yen-Ching; Giovannucci, Edward; Lazarus, Ross; Kraft, Peter; Ketkar, Shamika; Hunter, David J

2005-12-15

Chronic inflammation has been hypothesized to be a risk factor for prostate cancer. The Toll-like receptor 4 (TLR4) presents the bacterial lipopolysaccharide (LPS), which interacts with ligand-binding protein and CD14 (LPS receptor) and activates expression of inflammatory genes through nuclear factor-kappaB and mitogen-activated protein kinase signaling. A previous case-control study found a modest association of a polymorphism in the TLR4 gene [11381G/C, GG versus GC/CC: odds ratio (OR), 1.26] with risk of prostate cancer. We assessed if sequence variants of TLR4 were associated with the risk of prostate cancer. In a nested case-control design within the Health Professionals Follow-up Study, we identified 700 participants with prostate cancer diagnosed after they had provided a blood specimen in 1993 and before January 2000. Controls were 700 age-matched men without prostate cancer who had had a prostate-specific antigen test after providing a blood specimen. We genotyped 16 common (>5%) single nucleotide polymorphisms (SNP) discovered in a resequencing study spanning TLR4 to test for association between sequence variation in TLR4 and prostate cancer. Homozygosity for the variant alleles of eight SNPs was associated with a statistically significantly lower risk of prostate cancer (TLR4_1893, TLR4_2032, TLR4_2437, TLR4_7764, TLR4_11912, TLR4_16649, TLR4_17050, and TLR4_17923), but the TLR4_15844 polymorphism corresponding to 11381G/C was not associated with prostate cancer (GG versus CG/CC: OR, 1.01; 95% confidence interval, 0.79-1.29). Six common haplotypes (cumulative frequency, 81%) were observed; the global test for association between haplotypes and prostate cancer was statistically significant (chi(2) = 14.8 on 6 degrees of freedom; P = 0.02). Two common haplotypes were statistically significantly associated with altered risk of prostate cancer. Inherited polymorphisms of the innate immune gene TLR4 are associated with risk of prostate cancer.

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.

What do prostate cancer patients die of?

PubMed

Riihimäki, Matias; Thomsen, Hauke; Brandt, Andreas; Sundquist, Jan; Hemminki, Kari

2011-01-01

A recent rise in the incidence of prostate cancer and a more favorable outcome have increased the proportions of other causes of death in affected men. Extending the survival of prostate cancer patients thus requires knowledge of all causes of death. Data on the population, cancers, and causes of death were gathered from the nationwide Swedish Family-Cancer Database. A Cox regression model, comparing prostate cancer patients with all other men, was applied. Hazard ratios (HR) were calculated both for the underlying cause and for dying with a specific cause listed among multiple causes of death. Among 686,500 observed deaths, 62,500 were prostate cancer patients. For underlying causes other than prostate cancer, the highest cause-specific HRs were found for external causes (HR, 1.24; 95% confidence interval [CI], 1.16-1.31), diseases of the pulmonary circulation (HR, 1.22; 95% CI, 1.09-1.37), and heart failure (HR, 1.18; 95% CI, 1.11-1.24). For specific multiple causes, the highest HRs were found for anemia (HR, 2.28; 95% CI, 2.14-2.42), diseases of the pulmonary circulation (HR, 1.61; 95% CI, 1.55-1.68), and urinary system disease (HR, 1.90; 95% CI, 1.84-1.96). Prostate cancer patients have a higher risk for dying from various causes other than prostate cancer, including external causes and heart failure. Mechanisms have been proposed linking these elevated risks to both cancer and treatment. More attention should be paid to comorbidities in men with prostate cancer. The present study fulfills a gap in the knowledge of death causes in prostate cancer patients.

Abiraterone acetate in the treatment of prostate cancer.

PubMed

Thakur, Abhimanyu; Roy, Aishwarya; Ghosh, Arijit; Chhabra, Mohit; Banerjee, Sugato

2018-05-01

Among all cancer-related death, prostate cancer accounts for the second prominent reason for cancer-associated death in men. Despite the castration mediated reduction in testosterone synthesis, adrenal glands, as well as tissues of prostate cancer, continue to produce androgens, which ultimately lead to the growth of prostate cancer. This phase is referred as metastatic castration-resistant prostate cancer, which throws an obstacle to treatment. Androgen antagonists, in addition to deprivation of hormone, is being used for reducing the level of prostate-specific antigen but has not successfully come in front as a choice for prolonging the life of patients suffering from prostate cancer. In this prevailing scenario, abiraterone acetate (AA) has proved to be a boon for patients suffering from prostate cancer. AA selectively inhibits the actions of enzymes C17, 20-lyase and 17α-hydroxylase on cytochrome P450 (CYP) 17 when administered orally. The signaling of androgen receptor, being important for primary to metastatic phases of prostate cancer, CYP17 is essential for the synthesis of androgen. Herein, the in-detail pharmacological profile of AA, including androgen signaling, mechanism of action of AA, mechanism of AA resistance, pharmacokinetics, latest clinical findings, predictive markers, optimal treatment sequence, toxicity, and food interaction profiles have been reviewed. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Patient educational technologies and their use by patients diagnosed with localized prostate cancer.

PubMed

Baverstock, Richard J; Crump, R Trafford; Carlson, Kevin V

2015-09-29

Two urology practices in Calgary, Canada use patient educational technology (PET) as a core component of their clinical practice. The purpose of this study was to determine how patients interact with PET designed to inform them about their treatment options for clinically localized prostate cancer. A PET library was developed with 15 unique prostate-related educational modules relating to diagnosis, treatment options, and potential side effects. The PET collected data regarding its use, and those data were used to conduct a retrospective analysis. Descriptive analyses were conducted and comparisons made between patients' utilization of the PET library during first and subsequent access; Pearson's Chi-Square was used to test for statistical significance, where appropriate. Every patient (n = 394) diagnosed with localized prostate cancer was given access to the PET library using a unique identifier. Of those, 123 logged into the library and viewed at least one module and 94 patients logged into the library more than once. The average patient initially viewed modules pertaining to their diagnosis. Viewing behavior significantly changed in subsequent logins, moving towards modules pertaining to treatment options, decision making, and post-surgical information. As observed through the longitudinal utilization of the PET library, information technology offers clinicians an opportunity to provide an interactive platform to meet patients' dynamic educational needs. Understanding these needs will help inform the development of more useful PETs. The informational needs of patients diagnosed with clinically localized prostate cancer changed throughout the course of their diagnosis and treatment.

Wnt Signaling in Prostate Cancer Bone Metastases

DTIC Science & Technology

2015-09-01

Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Ace-1-Dkk-1, a canine prostate cancer overexpressing Dkk-1 is used in this study to investigate how...Dkk-1 expression in prostate cancer could change the metastatic phenotype and tumor growth in vivo. Ace-1-Dkk-1, a canine prostate cancer

Cross-cultural adaptation and validation of the French version of the Expanded Prostate cancer Index Composite questionnaire for health-related quality of life in prostate cancer patients.

PubMed

Anota, Amélie; Mariet, Anne-Sophie; Maingon, Philippe; Joly, Florence; Bosset, Jean-François; Guizard, Anne-Valérie; Bittard, Hugues; Velten, Michel; Mercier, Mariette

2016-12-06

Health-related quality of life (HRQoL) has been positioned as one of the major endpoints in oncology. Thus, there is a need to validate cancer-site specific survey instruments. This study aimed to perform a transcultural adaptation of the 50-item Expanded Prostate cancer Index Composite (EPIC) questionnaire for HRQoL in prostate cancer patients and to validate the psychometric properties of the French-language version. The EPIC questionnaire measures urinary, bowel, sexual and hormonal domains. The first step, corresponding to transcultural adaptation of the original English version of the EPIC was performed according to the back translation technique. The second step, comprising the validation of the psychometric properties of the EPIC questionnaire, was performed in patients under treatment for localized prostate cancer (treatment group) and in patients cured of prostate cancer (cured group). The EORTC QLQ-C30 and QLQ-PR25 prostate cancer module were also completed by patients to assess criterion validity. Two assessments were performed, i.e., before and at the end of treatment for the Treatment group, to assess sensitivity to change; and at 2 weeks' interval in the Cured group to assess test-retest reliability. Psychometric properties were explored according to classical test theory. The first step showed overall good acceptability and understanding of the questionnaire. In the second step, 215 patients were included from January 2012 to June 2014: 125 in the Treatment group, and 90 in the Cured group. All domains exhibited good internal consistency, except the bowel domain (Cronbach's α = 0.61). No floor effect was observed. Test-retest reliability assessed in the cured group was acceptable, expect for bowel function (intraclass coefficient = 0.68). Criterion validity was good for each domain and subscale. Construct validity was not demonstrated for the hormonal and bowel domains. Sensitivity to change was exhibited for 5/8 subscales and 2/4 summary scores for patients who experienced toxicities during treatment. The French EPIC questionnaire seems to have adequate psychometric properties, comparable to those exhibited by the original English-language version, except for the construct validity, which was not available in original version.

An Analytical Study of Prostate-Specific Antigen Dynamics.

PubMed

Esteban, Ernesto P; Deliz, Giovanni; Rivera-Rodriguez, Jaileen; Laureano, Stephanie M

2016-01-01

The purpose of this research is to carry out a quantitative study of prostate-specific antigen dynamics for patients with prostatic diseases, such as benign prostatic hyperplasia (BPH) and localized prostate cancer (LPC). The proposed PSA mathematical model was implemented using clinical data of 218 Japanese patients with histological proven BPH and 147 Japanese patients with LPC (stages T2a and T2b). For prostatic diseases (BPH and LPC) a nonlinear equation was obtained and solved in a close form to predict PSA progression with patients' age. The general solution describes PSA dynamics for patients with both diseases LPC and BPH. Particular solutions allow studying PSA dynamics for patients with BPH or LPC. Analytical solutions have been obtained and solved in a close form to develop nomograms for a better understanding of PSA dynamics in patients with BPH and LPC. This study may be useful to improve the diagnostic and prognosis of prostatic diseases.

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

Does Core Length Taken per cc of Prostate Volume in Prostate Biopsy Affect the Diagnosis of Prostate Cancer?

PubMed

Deliktas, Hasan; Sahin, Hayrettin; Cetinkaya, Mehmet; Dere, Yelda; Erdogan, Omer; Baldemir, Ercan

2016-08-01

The aim of this study was to determine the minimal core length to be taken per cc of prostate volume for an effective prostate biopsy. A retrospective analysis was performed on the records of 379 patients who underwent a first prostate biopsy with 12 to 16 cores under transrectal ultrasound guidance between September 2012 and April 2015. For each patient, the core length per cc of the prostate and the percentage of sampled prostate volume were calculated, and these values were compared between the patients with and without prostate cancer. A total of 348 patients were included in the study. Cancer was determined in 26.4% of patients. The mean core length taken per cc of prostate and the percentage of sampled prostate volume were determined to be 3.40 ± 0.15 mm/cc (0.26%; range, 0.08-0.63 cc) in patients with cancer and 2.75 ± 0.08 mm/cc (0.20%; range, 0.04-0.66 cc) in patients without cancer (P = .000 and P = .000), respectively. Core length taken per cc of prostate of > 3.31 mm/cc was found to be related to an increase in the rates of prostate cancer diagnosis (odds ratio, 2.84; 95% confidence interval, 1.68-4.78). The rate of cancer determination for core length taken per cc of prostate of < 3.31 mm/cc was 19.9% and of > 3.31 mm/cc, 41.1%. Core length taken per cc of prostate and the percentage of sampled prostate volume are important morphometric parameters in the determination of prostate cancer. The results of study suggest a core length per cc of the prostate of > 3.31 mm/cc as a cutoff value for quality assurance. Copyright © 2016 Elsevier Inc. All rights reserved.

Prostate cancer: The main risk and protective factors-Epigenetic modifications.

PubMed

Adjakly, Mawussi; Ngollo, Marjolaine; Dagdemir, Aslihan; Judes, Gaëlle; Pajon, Amaury; Karsli-Ceppioglu, Seher; Penault-Llorca, Frédérique; Boiteux, Jean-Paul; Bignon, Yves-Jean; Guy, Laurent; Bernard-Gallon, Dominique

2015-02-01

With 13 million new cases worldwide every year, prostate cancer is as a very real public health concern. Prostate cancer is common in over-50s men and the sixth-leading cause of cancer-related death in men worldwide. Like all cancers, prostate cancer is multifactorial - there are non-modifiable risk factors like heredity, ethnicity and geographic location, but also modifiable risk factors such as diet. Diet-cancer linkages have risen to prominence in the last few years, with accruing epidemiological data pointing to between-population incidence differentials in numerous cancers. Indeed, there are correlations between fat-rich diet and risk of hormone-dependent cancers like prostate cancer and breast cancer. Diet is a risk factor for prostate cancer, but certain micronutrients in specific diets are considered protective factors against prostate cancer. Examples include tomato lycopene, green tea epigallocatechin gallate, and soy phytoestrogens. These micronutrients are thought to exert cancer-protective effects via anti-oxidant pathways and inhibition of cell proliferation. Here, we focus in on the effects of phytoestrogens, and chiefly genistein and daidzein, which are the best-researched to date. Soy phytoestrogens are nonsteroid molecules whose structural similarity lends them the ability to mimic the effects of 17ß-estradiol. On top of anti-oxidant effects, there is evidence that soy phytoestrogens can modulate the epigenetic modifications found in prostate cancer. We also studied the impact of phytoestrogens on epigenetic modifications in prostate cancer, with special focus on DNA methylation, miRNA-mediated regulation and histone modifications. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

MD-miniRNA could be a more accurate biomarker for prostate cancer screening compared with serum prostate-specific antigen level.

PubMed

Xue, Dong; Zhou, Cui-Xing; Shi, Yun-Bo; Lu, Hao; He, Xiao-Zhou

2015-05-01

Prostate cancer and prostatic hyperplasia detection remains a great challenge, lacking of effective non-invasive and specific diagnostic biomarkers. In the current study, we aimed to identify the relative expression of plasma MD-miniRNA and its diagnostic performance in differentiating prostate cancer and prostatic hyperplasia patients from healthy controls, compared with serum prostate-specific antigen (PSA) level. All of the clinical participants (63 prostate cancer patients, 32 prostatic hyperplasia patients, and 50 healthy controls) were obtained from the Third Affiliated Hospital of Suzhou University in China between January 2013 and April 2014. Clinical characteristics were well matched. Plasma samples were extracted to test the relative expression of MD-miniRNA using the method of qRT-PCR. SPSS 22.0 statistical software package was used to analyze the data and GraphPad Prism 6.0 was used to generate the graphs. Relativity expression of plasma MD-miniRNA was significantly upregulated in prostate cancer, compared with prostatic hyperplasia patients and healthy controls. Serum PSA level revealed similar differences among these groups. MD-miniRNA presented a relatively high diagnostic accuracy with AUC of 0.86 (95 % CI 0.80-0.93) in differentiating prostate cancer patients from healthy controls. Simultaneously, MD-miniRNA was able to discriminate prostate cancer patients from prostatic hyperplasia controls with AUC of 0.79 (95 % CI 0.70-0.88). In addition, MD-miniRNA displayed a better diagnostic performance than PSA level. However, the panel of these two biomarkers revealed the best diagnostic performance, compared with either single biomarker. Results of this study showed that plasma MD-miniRNA could serve as a promising and noninvasive biomarker for diagnosing prostate cancer. Further large-scale studies are needed to confirm its clinical diagnosis accuracy.

Risk Analysis of Prostate Cancer in PRACTICAL, a Multinational Consortium, Using 25 Known Prostate Cancer Susceptibility Loci.

PubMed

Amin Al Olama, Ali; Benlloch, Sara; Antoniou, Antonis C; Giles, Graham G; Severi, Gianluca; Neal, David E; Hamdy, Freddie C; Donovan, Jenny L; Muir, Kenneth; Schleutker, Johanna; Henderson, Brian E; Haiman, Christopher A; Schumacher, Fredrick R; Pashayan, Nora; Pharoah, Paul D P; Ostrander, Elaine A; Stanford, Janet L; Batra, Jyotsna; Clements, Judith A; Chambers, Suzanne K; Weischer, Maren; Nordestgaard, Børge G; Ingles, Sue A; Sorensen, Karina D; Orntoft, Torben F; Park, Jong Y; Cybulski, Cezary; Maier, Christiane; Doerk, Thilo; Dickinson, Joanne L; Cannon-Albright, Lisa; Brenner, Hermann; Rebbeck, Timothy R; Zeigler-Johnson, Charnita; Habuchi, Tomonori; Thibodeau, Stephen N; Cooney, Kathleen A; Chappuis, Pierre O; Hutter, Pierre; Kaneva, Radka P; Foulkes, William D; Zeegers, Maurice P; Lu, Yong-Jie; Zhang, Hong-Wei; Stephenson, Robert; Cox, Angela; Southey, Melissa C; Spurdle, Amanda B; FitzGerald, Liesel; Leongamornlert, Daniel; Saunders, Edward; Tymrakiewicz, Malgorzata; Guy, Michelle; Dadaev, Tokhir; Little, Sarah J; Govindasami, Koveela; Sawyer, Emma; Wilkinson, Rosemary; Herkommer, Kathleen; Hopper, John L; Lophatonanon, Aritaya; Rinckleb, Antje E; Kote-Jarai, Zsofia; Eeles, Rosalind A; Easton, Douglas F

2015-07-01

Genome-wide association studies have identified multiple genetic variants associated with prostate cancer risk which explain a substantial proportion of familial relative risk. These variants can be used to stratify individuals by their risk of prostate cancer. We genotyped 25 prostate cancer susceptibility loci in 40,414 individuals and derived a polygenic risk score (PRS). We estimated empirical odds ratios (OR) for prostate cancer associated with different risk strata defined by PRS and derived age-specific absolute risks of developing prostate cancer by PRS stratum and family history. The prostate cancer risk for men in the top 1% of the PRS distribution was 30.6 (95% CI, 16.4-57.3) fold compared with men in the bottom 1%, and 4.2 (95% CI, 3.2-5.5) fold compared with the median risk. The absolute risk of prostate cancer by age of 85 years was 65.8% for a man with family history in the top 1% of the PRS distribution, compared with 3.7% for a man in the bottom 1%. The PRS was only weakly correlated with serum PSA level (correlation = 0.09). Risk profiling can identify men at substantially increased or reduced risk of prostate cancer. The effect size, measured by OR per unit PRS, was higher in men at younger ages and in men with family history of prostate cancer. Incorporating additional newly identified loci into a PRS should improve the predictive value of risk profiles. We demonstrate that the risk profiling based on SNPs can identify men at substantially increased or reduced risk that could have useful implications for targeted prevention and screening programs. ©2015 American Association for Cancer Research.

Pilot Comparison of ⁶⁸Ga-RM2 PET and ⁶⁸Ga-PSMA-11 PET in Patients with Biochemically Recurrent Prostate Cancer.

PubMed

Minamimoto, Ryogo; Hancock, Steven; Schneider, Bernadette; Chin, Frederick T; Jamali, Mehran; Loening, Andreas; Vasanawala, Shreyas; Gambhir, Sanjiv Sam; Iagaru, Andrei

2016-04-01

Glu-NH-CO-NH-Lys-(Ahx)-[(68)Ga(HBED-CC)] ((68)Ga-PSMA-11) is a PET tracer that can detect prostate cancer relapses and metastases by binding to the extracellular domain of PSMA. (68)Ga-labeled DOTA-4-amino-1-carboxymethyl-piperidine-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 ((68)Ga-RM2) is a synthetic bombesin receptor antagonist that targets gastrin-releasing peptide receptors. We present pilot data on the biodistribution of these PET tracers in a small cohort of patients with biochemically recurrent prostate cancer. Seven men (mean age ± SD, 74.3 ± 5.9 y) with biochemically recurrent prostate cancer underwent both (68)Ga-PSMA-11 PET/CT and (68)Ga-RM2 PET/MRI scans. SUVmax and SUVmean were recorded for normal tissues and areas of uptake outside the expected physiologic biodistribution. All patients had a rising level of prostate-specific antigen (mean ± SD, 13.5 ± 11.5) and noncontributory results on conventional imaging. (68)Ga-PSMA-11 had the highest physiologic uptake in the salivary glands and small bowel, with hepatobiliary and renal clearance noted, whereas (68)Ga-RM2 had the highest physiologic uptake in the pancreas, with renal clearance noted. Uptake outside the expected physiologic biodistribution did not significantly differ between (68)Ga-PSMA-11 and (68)Ga-RM2; however, (68)Ga-PSMA-11 localized in a lymph node and seminal vesicle in a patient with no abnormal (68)Ga-RM2 uptake. Abdominal periaortic lymph nodes were more easily visualized by(68)Ga-RM2 in two patients because of lack of interference by radioactivity in the small intestine. (68)Ga-PSMA-11 and (68)Ga-RM2 had distinct biodistributions in this small cohort of patients with biochemically recurrent prostate cancer. Additional work is needed to understand the expression of PSMA and gastrin-releasing peptide receptors in different types of prostate cancer. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Differential Splicing of Oncogenes and Tumor Suppressor Genes in African- and Caucasian-American Populations: Contributing Factor in Prostate Cancer Disparities

DTIC Science & Technology

2015-10-01

Populations: Contributing Factor in Prostate Cancer Disparities? PRINCIPAL INVESTIGATOR: Norman H Lee, Ph.D. CONTRACTING ORGANIZATION: George Washington...Prostate Cancer Disparities? 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Norman H Lee, PhD; Bi-Dar Wang, PhD; Jacqueline Olender (PhD graduate...suppressor genes in prostate cancer disparities between African American (AA) and Caucasian American (CA) prostate cancer (PCa). In year 1 of this award

Using T2-Exchange from Ln3+DOTA-Based Chelates for Contrast-Enhanced Molecular Imaging of Prostate Cancer with MRI

DTIC Science & Technology

2015-04-01

antigen ( PSMA ) of prostate cancer cells would then be synthesized and tested with both in vitro and in vivo experiments. Major Findings: We found that the...simplified chemistry. 15. SUBJECT TERMS MRI Contrast Agent, T2 contrast, Prostate Cancer, PSMA Targeted Agent, Early Detection and Diagnosis, Dysprosium... PSMA ), which is significantly over-expressed by prostate cancer cells, has proven to be an excellent target for imaging prostate cancer in mouse

SSeCKS/AKAP12 induces repulsion between human prostate cancer and microvessel endothelial cells through the activation of Semaphorin 3F.

PubMed

Xie, Wen; Su, Wei; Zhang, Lijuan; Shang, Qingkun; Su, Bing

2017-09-02

Metastasis remains the primary cause of prostate cancer related death. Cancer cells need to contact endothelial cells and disrupt endothelial junctions to cross the endothelium for invasion and metastasis. The suppression of heterotypic repulsion between cancer and endothelial cells allows cancer cells to invade into the surrounding tissue. Here, we demonstrate that SSeCKS/AKAP12 induced repulsion between human prostate cancer and microvessel endothelial cells, which was mediated by an angiogenesis inhibitor Semaphorin 3F. Moreover, we examined AKAP12 and Semaphorin 3F mRNA expression in 42 prostate cancer and 30 benign prostatic hyperplasia tissue samples, and found that the expression of AKAP12 and Semaphorin 3F mRNA was inversely associated with the degree of aggressiveness of prostate cancer cells and tissues. An ordinal logistic regression analysis indicates that there is a positive association between the expression of AKAP12 and Semaphorin 3F in prostate cancer, suggesting that the activation of Semaphorin 3F by SSeCKS/AKAP12 may be involved in prostate cancer progression and metastasis. Copyright © 2017 Elsevier Inc. All rights reserved.

Patterns of care in palliative radiotherapy: a population-based study.

PubMed

Murphy, James D; Nelson, Lorene M; Chang, Daniel T; Mell, Loren K; Le, Quynh-Thu

2013-09-01

Approximately one half of the radiotherapy (RT) prescribed in the United States is delivered with palliative intent. The purpose of this study was to investigate the patterns of delivery of palliative RT across the United States. Using the Surveillance, Epidemiology, and End Results-Medicare linked database, 51,610 patients were identified with incident stage IV breast, prostate, lung, or colorectal cancer diagnosed between 2000 and 2007 and observed through 2009. Multivariate logistic regression determined predictors of palliative RT. Forty-one percent of the study population received palliative RT, including 53% of patients with lung cancer, followed by those with breast (42%), prostate (40%), and colorectal cancers (12%). Multivariate analysis revealed that older patients (P<.001) and those with higher Charlson comorbidity scores (P<.001) were less likely to receive palliative RT. Black patients with prostate cancer were 20% less likely (P<.001), and black patients with colorectal cancer were 28% less likely (P<.001), than white patients to receive palliative RT. Among those treated with RT, 23% of patients with lung cancer died within 2 weeks of completing treatment, followed by those with colorectal (12%), breast (11%), and prostate cancers (8%). In addition to tumor site, significant predictors (P<.05) of death within 2 weeks of receiving RT included increased age, increased comorbidity, and male sex. Inequality in the receipt of palliative RT exists among the elderly and patients with comorbid conditions and varies with race. In addition, a significant number of patients die shortly after receiving RT. Understanding these patterns of care, along with further research into the underlying causes, will improve access and quality of palliative RT.

Characterizing the Hypermutated Subtype of Advanced Prostate Cancer as a Predictive Biomarker for Precision Medicine

DTIC Science & Technology

2017-10-01

goal of this research is to characterize the mechanisms leading to hypermutated prostate cancer and to integrate tumor hypermutation status with... integrate tumor hypermutation status with clinical decision making and therapy to improve the care of men with advanced prostate cancer. Using Next-Gen...preparation of presentations that integrate prostate cancer patient clinical histories with genomic findings 1-36 Yes, see Prostate Precision Tumor

Thioredoxin 1 in Prostate Tissue Is Associated with Gleason Score, Erythrocyte Antioxidant Enzyme Activity, and Dietary Antioxidants.

PubMed

Vance, Terrence M; Azabdaftari, Gissou; Pop, Elena A; Lee, Sang Gil; Su, L Joseph; Fontham, Elizabeth T H; Bensen, Jeannette T; Steck, Susan E; Arab, Lenore; Mohler, James L; Chen, Ming-Hui; Koo, Sung I; Chun, Ock K

2015-01-01

Background. Prostate cancer is the most common noncutaneous cancer and second leading cause of cancer-related mortality in men in the US. Growing evidence suggests that oxidative stress is involved in prostate cancer. Methods. In this study, thioredoxin 1 (Trx 1), an enzyme and subcellular indicator of redox status, was measured in prostate biopsy tissue from 55 men from the North Carolina-Louisiana Prostate Cancer Project. A pathologist blindly scored levels of Trx 1. The association between Trx 1 and the Gleason score, erythrocyte antioxidant enzyme activity, and dietary antioxidant intake was determined using Fisher's exact test. Results. Trx 1 levels in benign prostate tissue in men with incident prostate cancer were positively associated with the Gleason score (P = 0.01) and inversely associated with dietary antioxidant intake (P = 0.03). In prostate cancer tissue, Trx 1 levels were associated with erythrocyte glutathione peroxidase activity (P = 0.01). No association was found for other erythrocyte enzymes. Greater Gleason score of malignant tissue corresponds to a greater difference in Trx 1 levels between malignant and benign tissue (P = 0.04). Conclusion. These results suggest that the redox status of prostate tissue is associated with prostate cancer grade and both endogenous and exogenous antioxidants.

The role of positron emission tomography/computed tomography imaging with radiolabeled choline analogues in prostate cancer.

PubMed

Navarro-Pelayo Láinez, M M; Rodríguez-Fernández, A; Gómez-Río, M; Vázquez-Alonso, F; Cózar-Olmo, J M; Llamas-Elvira, J M

2014-11-01

prostate cancer is the most frequent solid malignant tumor in Western Countries. Positron emission tomography/x-ray computed tomography imaging with radiolabeled choline analogues is a useful tool for restaging prostate cancer in patients with rising prostate-specific antigen after radical treatment (in whom conventional imaging techniques have important limitations) as well as in the initial assessment of a selected group of prostate cancer patients. For this reason a literature review is necessary in order to evaluate the usefulness of this imaging test for the diagnosis and treatment of prostate cancer. a MEDLINE (PubMed way) literature search was performed using the search parameters: «Prostate cancer» and «Choline-PET/CT». Other search terms were «Biochemical failure» and/or «Staging» and/or «PSA kinetics». English and Spanish papers were selected; original articles, reviews, systematic reviews and clinical guidelines were included. according to available data, radiolabeled choline analogues plays an important role in the management of prostate cancer, especially in biochemical relapse because technique accuracy is properly correlated with prostate-specific antigen values and kinetics. Although is an emerging diagnostic technique useful in treatment planning of prostate cancer, final recommendations have not been submitted. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

Identification and Validation of Potential New Biomarkers for Prostate Cancer Diagnosis and Prognosis Using 2D-DIGE and MS

PubMed Central

Geisler, Cordelia; Gaisa, Nadine T.; Pfister, David; Fuessel, Susanne; Kristiansen, Glen; Braunschweig, Till; Gostek, Sonja; Beine, Birte; Diehl, Hanna C.; Jackson, Angela M.; Borchers, Christoph H.; Heidenreich, Axel; Meyer, Helmut E.; Knüchel, Ruth; Henkel, Corinna

2015-01-01

This study was designed to identify and validate potential new biomarkers for prostate cancer and to distinguish patients with and without biochemical relapse. Prostate tissue samples analyzed by 2D-DIGE (two-dimensional difference in gel electrophoresis) and mass spectrometry (MS) revealed downregulation of secernin-1 (P < 0.044) in prostate cancer, while vinculin showed significant upregulation (P < 0.001). Secernin-1 overexpression in prostate tissue was validated using Western blot and immunohistochemistry while vinculin expression was validated using immunohistochemistry. These findings indicate that secernin-1 and vinculin are potential new tissue biomarkers for prostate cancer diagnosis and prognosis, respectively. For validation, protein levels in urine were also examined by Western blot analysis. Urinary vinculin levels in prostate cancer patients were significantly higher than in urine from nontumor patients (P = 0.006). Using multiple reaction monitoring-MS (MRM-MS) analysis, prostatic acid phosphatase (PAP) showed significant higher levels in the urine of prostate cancer patients compared to controls (P = 0.012), while galectin-3 showed significant lower levels in the urine of prostate cancer patients with biochemical relapse, compared to those without relapse (P = 0.017). Three proteins were successfully differentiated between patients with and without prostate cancer and patients with and without relapse by using MRM. Thus, this technique shows promise for implementation as a noninvasive clinical diagnostic technique. PMID:25667921

Prostate cancer diagnosis in a resource-poor setting: the changing role of digital rectal examination.

PubMed

Ahmed, Muhammed

2011-07-01

We undertook this study in order to determine the current role of digital rectal examination (DRE) in the diagnosis of prostate cancer in a resource-poor setting. The diagnosis of prostate cancer has been revolutionized by the introduction of prostate-specific antigen (PSA), transrectal ultrasound (TRUS) for biopsy guidance and more efficient biopsy equipment, but they are not readily available in most developing countries. This is a prospective study of 131 patients with suspected prostate cancer based on clinical presentation, DRE and elevated PSA. The presence or absence of cancer was confirmed by biopsy and histologic examination. Patients with screen- or incidentally-detected prostate cancer were excluded. The most common symptom was the development of lower urinary tract symptoms (LUTS). All patients had abnormal DRE and indurated prostate was the most frequent finding (50%). The mean PSA was 33.9 ng/mL: of the 131 patients, 80 (61.1%) had a malignant histology following biopsy, 47 (35.9%) were benign and four (3.0%) were prostate intraepithelial neoplasia (PIN). The low specificity of DRE in the diagnosis of prostate cancer requires that it should be combined with other diagnostic modalities such as PSA and TRUS-guided prostate biopsy. Thus government and health-care providers in resource-poor countries must strive to make these facilities available in order to improve prostate cancer diagnosis.

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.).

Biomarkers in localized prostate cancer

PubMed Central

Ferro, Matteo; Buonerba, Carlo; Terracciano, Daniela; Lucarelli, Giuseppe; Cosimato, Vincenzo; Bottero, Danilo; Deliu, Victor M; Ditonno, Pasquale; Perdonà, Sisto; Autorino, Riccardo; Coman, Ioman; De Placido, Sabino; Di Lorenzo, Giuseppe; De Cobelli, Ottavio

2016-01-01

Biomarkers can improve prostate cancer diagnosis and treatment. Accuracy of prostate-specific antigen (PSA) for early diagnosis of prostate cancer is not satisfactory, as it is an organ- but not cancer-specific biomarker, and it can be improved by using models that incorporate PSA along with other test results, such as prostate cancer antigen 3, the molecular forms of PSA (proPSA, benign PSA and intact PSA), as well as kallikreins. Recent reports suggest that new tools may be provided by metabolomic studies as shown by preliminary data on sarcosine. Additional molecular biomarkers have been identified by the use of genomics, proteomics and metabolomics. We review the most relevant biomarkers for early diagnosis and management of localized prostate cancer. PMID:26768791

Prostate Cancer Probability Prediction By Machine Learning Technique.

PubMed

Jović, Srđan; Miljković, Milica; Ivanović, Miljan; Šaranović, Milena; Arsić, Milena

2017-11-26

The main goal of the study was to explore possibility of prostate cancer prediction by machine learning techniques. In order to improve the survival probability of the prostate cancer patients it is essential to make suitable prediction models of the prostate cancer. If one make relevant prediction of the prostate cancer it is easy to create suitable treatment based on the prediction results. Machine learning techniques are the most common techniques for the creation of the predictive models. Therefore in this study several machine techniques were applied and compared. The obtained results were analyzed and discussed. It was concluded that the machine learning techniques could be used for the relevant prediction of prostate cancer.

Androgen deprivation and stem cell markers in prostate cancers

PubMed Central

Tang, Yao; Hamburger, Anne W; Wang, Linbo; Khan, Mohammad Afnan; Hussain, Arif

2010-01-01

In our previous studies using human LNCaP xenografts and TRAMP (transgenic adenocarcinoma of mouse prostate) mice, androgen deprivation therapy (ADT) resulted in a temporary cessation of prostate cancer (PCa) growth, but then tumors grew faster with more malignant behaviour. To understand whether cancer stem cells might play a role in PCa progression in these animal models, we investigated the expressions of stem cell-related markers in tumors at different time points after ADT. In both animal models, enhanced expressions of stem cell markers were observed in tumors of castrated mice, as compared to non-castrated controls. This increased cell population that expressed stem cell markers is designated as stem-like cells (SLC) in this article. We also observed that the SLC peaked at relatively early time points after ADT, before tumors resumed their growth. These results suggest that the SLC population may play a role in tumor re-growth and disease progression, and that targeting the SLC at their peak-expression time point may prevent tumor recurrence following ADT. PMID:20126580

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.

The HDL receptor SR-BI is associated with human prostate cancer progression and plays a possible role in establishing androgen independence.

PubMed

Schörghofer, David; Kinslechner, Katharina; Preitschopf, Andrea; Schütz, Birgit; Röhrl, Clemens; Hengstschläger, Markus; Stangl, Herbert; Mikula, Mario

2015-08-07

Human prostate cancer represents one of the most frequently diagnosed cancers in men worldwide. Currently, diagnostic methods are insufficient to identify patients at risk for aggressive prostate cancer, which is essential for early treatment. Recent data indicate that elevated cholesterol levels in the plasma are a prerequisite for the progression of prostate cancer. Here, we analyzed clinical prostate cancer samples for the expression of receptors involved in cellular cholesterol uptake. We screened mRNA microarray files of prostate cancer samples for alterations in the expression levels of cholesterol transporters. Furthermore, we performed immunohistochemistry analysis on human primary prostate cancer tissue sections derived from patients to investigate the correlation of SR-BI with clinicopathological parameters and the mTOR target pS6. In contrast to LDLR, we identified SR-BI mRNA and protein expression to be induced in high Gleason grade primary prostate cancers. Histologic analysis of prostate biopsies revealed that 53.6 % of all cancer samples and none of the non-cancer samples showed high SR-BI staining intensity. The disease-free survival time was reduced (P = 0.02) in patients expressing high intra-tumor levels of SR-BI. SR-BI mRNA correlated with HSD17B1 and HSD3B1 and SR-BI protein staining showed correlation with active ribosomal protein S6 (RS = 0.828, P < 0.00001). We identified SR-BI to indicate human prostate cancer formation, suggesting that increased levels of SR-BI may be involved in the generation of a castration-resistant phenotype.

Prostate stromal cells express the progesterone receptor to control cancer cell mobility.

PubMed

Yu, Yue; Lee, Jennifer Suehyun; Xie, Ning; Li, Estelle; Hurtado-Coll, Antonio; Fazli, Ladan; Cox, Michael; Plymate, Stephen; Gleave, Martin; Dong, Xuesen

2014-01-01

Reciprocal interactions between epithelium and stroma play vital roles for prostate cancer development and progression. Enhanced secretions of cytokines and growth factors by cancer associated fibroblasts in prostate tumors create a favorable microenvironment for cancer cells to grow and metastasize. Our previous work showed that the progesterone receptor (PR) was expressed specifically in prostate stromal fibroblasts and smooth muscle cells. However, the expression levels of PR and its impact to tumor microenvironment in prostate tumors are poorly understood. Immunohistochemistry assays are applied to human prostate tissue biopsies. Cell migration, invasion and proliferation assays are performed using human prostate cells. Real-time PCR and ELISA are applied to measure gene expression at molecular levels. Immunohistochemistry assays showed that PR protein levels were decreased in cancer associated stroma when compared with paired normal prostate stroma. Using in vitro prostate stromal cell models, we showed that conditioned media collected from PR positive stromal cells inhibited prostate cancer cell migration and invasion, but had minor suppressive impacts on cancer cell proliferation. PR suppressed the secretion of stromal derived factor-1 (SDF-1) and interlukin-6 (IL-6) by stromal cells independent to PR ligands. Blocking PR expression by siRNA or supplementation of exogenous SDF-1 or IL-6 to conditioned media from PR positive stromal cells counteracted the inhibitory effects of PR to cancer cell migration and invasion. Decreased expression of the PR in cancer associated stroma may contribute to the elevated SDF-1 and IL-6 levels in prostate tumors and enhance prostate tumor progression.

Combining immunotherapies for the treatment of prostate cancer.

PubMed

Redman, Jason M; Gulley, James L; Madan, Ravi A

2017-12-01

Sipuleucel-T, a therapeutic dendritic-cell vaccine, was Food and Drug Administration-approved for prostate cancer in 2010. No new immunotherapies for prostate cancer have been approved since. However, novel agents and combination approaches offer great promise for improving outcomes for prostate cancer patients. Here we review the latest developments in immunotherapy for prostate cancer. Sipuleucel-T has demonstrated a survival advantage of 4.1 months in metastatic castration-resistant prostate cancer. PSA-TRICOM (PROSTVAC), a prostate-specific antigen-targeted vaccine platform, showed evidence of clinical and immunologic efficacy in early-phase clinical trials, and results from a phase III trial in advanced disease are pending. While immune checkpoint inhibitors appear to have modest activity as monotherapy, preclinical and clinical data suggest that they may synergize with vaccines, poly [ADP-ribose] polymerase inhibitors, and other agents. Several clinical studies that combine these therapies are underway. Combining prostate cancer vaccines with immune checkpoint inhibitors has great potential for improving clinical outcomes in prostate cancer. Such combination approaches may create and then recruit tumor-specific T cells to tumor while also increasing their effector function. Other emerging agents may also enhance immune-mediated tumor destruction. Copyright © 2017. Published by Elsevier Inc.

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.

Identification of CD166 as a Surface Marker for Enriching Prostate Stem/Progenitor and Cancer Initiating Cells

PubMed Central

Wang, Shunyou; Tran, Linh M.; Goldstein, Andrew S.; Lawson, Devon; Chen, Donghui; Li, Yunfeng; Guo, Changyong; Zhang, Baohui; Fazli, Ladan; Gleave, Martin; Witte, Owen N.; Garraway, Isla P.; Wu, Hong

2012-01-01

New therapies for late stage and castration resistant prostate cancer (CRPC) depend on defining unique properties and pathways of cell sub-populations capable of sustaining the net growth of the cancer. One of the best enrichment schemes for isolating the putative stem/progenitor cell from the murine prostate gland is Lin-;Sca1+;CD49fhi (LSChi), which results in a more than 10-fold enrichment for in vitro sphere-forming activity. We have shown previously that the LSChi subpopulation is both necessary and sufficient for cancer initiation in the Pten-null prostate cancer model. To further improve this enrichment scheme, we searched for cell surface molecules upregulated upon castration of murine prostate and identified CD166 as a candidate gene. CD166 encodes a cell surface molecule that can further enrich sphere-forming activity of WT LSChi and Pten null LSChi. Importantly, CD166 could enrich sphere-forming ability of benign primary human prostate cells in vitro and induce the formation of tubule-like structures in vivo. CD166 expression is upregulated in human prostate cancers, especially CRPC samples. Although genetic deletion of murine CD166 in the Pten null prostate cancer model does not interfere with sphere formation or block prostate cancer progression and CRPC development, the presence of CD166 on prostate stem/progenitors and castration resistant sub-populations suggest that it is a cell surface molecule with the potential for targeted delivery of human prostate cancer therapeutics. PMID:22880034

Genetic Alterations in Prostate Cancers among African American Men and Comparisons with Cancers from European and Asian Patients

DTIC Science & Technology

2016-10-01

AWARD NUMBER: W81XWH-14-1-0303 TITLE: Genetic Alterations in Prostate Cancers among African-American Men and Comparisons with Cancers from...COVERED 29 Sep 2015 – 28 Sep 2016 4. TITLE AND SUBTITLE Genetic Alterations in Prostate Cancers among African- American Men and Comparisons with Cancers...identification of patients with aggressive PCa in African Americans. 15. SUBJECT TERMS Prostate cancer; genetics 16. SECURITY CLASSIFICATION OF

Genome-wide DNA methylation measurements in prostate tissues uncovers novel prostate cancer diagnostic biomarkers and transcription factor binding patterns.

PubMed

Kirby, Marie K; Ramaker, Ryne C; Roberts, Brian S; Lasseigne, Brittany N; Gunther, David S; Burwell, Todd C; Davis, Nicholas S; Gulzar, Zulfiqar G; Absher, Devin M; Cooper, Sara J; Brooks, James D; Myers, Richard M

2017-04-17

Current diagnostic tools for prostate cancer lack specificity and sensitivity for detecting very early lesions. DNA methylation is a stable genomic modification that is detectable in peripheral patient fluids such as urine and blood plasma that could serve as a non-invasive diagnostic biomarker for prostate cancer. We measured genome-wide DNA methylation patterns in 73 clinically annotated fresh-frozen prostate cancers and 63 benign-adjacent prostate tissues using the Illumina Infinium HumanMethylation450 BeadChip array. We overlaid the most significantly differentially methylated sites in the genome with transcription factor binding sites measured by the Encyclopedia of DNA Elements consortium. We used logistic regression and receiver operating characteristic curves to assess the performance of candidate diagnostic models. We identified methylation patterns that have a high predictive power for distinguishing malignant prostate tissue from benign-adjacent prostate tissue, and these methylation signatures were validated using data from The Cancer Genome Atlas Project. Furthermore, by overlaying ENCODE transcription factor binding data, we observed an enrichment of enhancer of zeste homolog 2 binding in gene regulatory regions with higher DNA methylation in malignant prostate tissues. DNA methylation patterns are greatly altered in prostate cancer tissue in comparison to benign-adjacent tissue. We have discovered patterns of DNA methylation marks that can distinguish prostate cancers with high specificity and sensitivity in multiple patient tissue cohorts, and we have identified transcription factors binding in these differentially methylated regions that may play important roles in prostate cancer development.

miR-888 is an expressed prostatic secretions-derived microRNA that promotes prostate cell growth and migration

PubMed Central

Lewis, Holly; Lance, Raymond; Troyer, Dean; Beydoun, Hind; Hadley, Melissa; Orians, Joseph; Benzine, Tiffany; Madric, Kenya; Semmes, O John; Drake, Richard; Esquela-Kerscher, Aurora

2014-01-01

microRNAs (miRNAs) are a growing class of small non-coding RNAs that exhibit widespread dysregulation in prostate cancer. We profiled miRNA expression in syngeneic human prostate cancer cell lines that differed in their metastatic potential in order to determine their role in aggressive prostate cancer. miR-888 was the most differentially expressed miRNA observed in human metastatic PC3-ML cells relative to non-invasive PC3-N cells, and its levels were higher in primary prostate tumors from cancer patients, particularly those with seminal vesicle invasion. We also examined a novel miRNA-based biomarker source called expressed prostatic secretions in urine (EPS urine) for miR-888 expression and found that its levels were preferentially elevated in prostate cancer patients with high-grade disease. These expression studies indicated a correlation for miR-888 in disease progression. We next tested how miR-888 regulated cancer-related pathways in vitro using human prostate cancer cell lines. Overexpression of miR-888 increased proliferation and migration, and conversely inhibition of miR-888 activity blocked these processes. miR-888 also increased colony formation in PC3-N and LNCaP cells, supporting an oncogenic role for this miRNA in the prostate. Our data indicates that miR-888 functions to promote prostate cancer progression and can suppress protein levels of the tumor suppressor genes RBL1 and SMAD4. This miRNA holds promise as a diagnostic tool using an innovative prostatic fluid source as well as a therapeutic target for aggressive prostate cancer. PMID:24200968

CCL11 (eotaxin-1): a new diagnostic serum marker for prostate cancer.

PubMed

Agarwal, Manisha; He, Chang; Siddiqui, Javed; Wei, John T; Macoska, Jill A

2013-05-01

The recent recommendation of the U.S. Preventive Services Task Force against PSA-based screening for prostate cancer was based, in part, on the lack of demonstrated diagnostic utility of serum PSA values in the low, but detectable range to successfully predict prostate cancer. Though controversial, this recommendation reinforced the critical need to develop, validate, and determine the utility of other serum and/or urine transcript and protein markers as diagnostic markers for PCa. The studies described here were intended to determine whether inflammatory cytokines might augment serum PSA as a diagnostic marker for prostate cancer. Multiplex ELISA assays were performed to quantify CCL1, CCL2, CCL5, CCL8, CCL11, CCL17, CXCL1, CXCL5, CXCL8, CXCL10, CXCL12, and IL-6 protein levels in the serum of 272 men demonstrating serum PSA values of <10 ng/ml and undergoing a 12 core diagnostic needle biopsy for detection of prostate cancer. Logistic regression was used to identify the associations between specific chemokines and prostate cancer status adjusted for prostate volume, and baseline PSA. Serum levels for CCL1 (I-309) were significantly elevated among all men with enlarged prostates (P < 0.04). Serum levels for CCL11 (Eotaxin-1) were significantly elevated among men with prostate cancer regardless of prostate size (P < 0.01). The remaining 10 cytokines examined in this study did not exhibit significant correlations with either prostate volume or cancer status. Serum CCL11 values may provide a useful diagnostic tool to help distinguish between prostatic enlargement and prostate cancer among men demonstrating low, but detectable, serum PSA values. Copyright © 2012 Wiley Periodicals, Inc.

Intracellular Propionibacterium acnes Infection in Glandular Epithelium and Stromal Macrophages of the Prostate with or without Cancer

PubMed Central

Bae, Yuan; Ito, Takashi; Iida, Tadatsune; Uchida, Keisuke; Sekine, Masaki; Nakajima, Yutaka; Kumagai, Jiro; Yokoyama, Tetsuji; Kawachi, Hiroshi; Akashi, Takumi; Eishi, Yoshinobu

2014-01-01

Background Recent reports on Propionibacterium acnes (P. acnes) suggest that this bacterium is prevalent in the prostate, is associated with acute and chronic prostatic inflammation, and might have a role in prostate carcinogenesis. Methods To evaluate the pathogenic role of this indigenous bacterium, we screened for the bacterium in radical prostatectomy specimens using enzyme immunohistochemistry with a novel P. acnes-specific monoclonal antibody (PAL antibody), together with an anti-nuclear factor-kappa B (NF-κB) antibody. We examined formalin-fixed and paraffin-embedded tissue sections of radical prostatectomy specimens from 28 patients with prostate cancer and 18 age-matched control patients with bladder cancer, but without prostate cancer. Results Immunohistochemistry with the PAL antibody revealed small round bodies within some non-cancerous glandular epithelium and stromal macrophages in most prostate samples. Prostate cancer samples had higher frequencies of either cytoplasmic P. acnes or nuclear NF-κB expression of glandular epithelium and higher numbers of stromal macrophages with P. acnes than control samples. These parameters were also higher in the peripheral zone than in the transitional zone of the prostate, especially in prostate cancer samples. Nuclear NF-κB expression was more frequent in glands with P. acnes than in glands without P. acnes. The number of stromal macrophages with the bacterium correlated with the grade of chronic inflammation in both the PZ and TZ areas and with the grade of acute inflammation in the TZ area. Conclusions Immunohistochemical analysis with a novel monoclonal antibody for detecting P. acnes in the prostate suggested that intraepithelial P. acnes infection in non-cancerous prostate glands and inflammation caused by the bacterium may contribute to the development of prostate cancer. PMID:24587325

Comparison of clinical and survival characteristics between prostate cancer patients of PSA-based screening and clinical diagnosis in China.

PubMed

Xu, Libo; Wang, Jinguo; Guo, Baofeng; Zhang, Haixia; Wang, Kaichen; Wang, Ding; Dai, Chang; Zhang, Ling; Zhao, Xuejian

2018-01-02

Prostate-specific antigen (PSA)-based mass screening remains the most controversial topic in prostate cancer. PSA-based mass screening has not been widely used in China yet. The aim of our study was to evaluate the effect of the PSA-based screening in China. The cohort consisted of 1,012 prostate cancer patients. Data were retrospectively collected and clinical characteristics of the cohorts were investigated. Survival was analyzed for prostatic carcinoma of both PSA screened and clinically diagnosed patients according to clinical characteristics and the National Comprehensive Cancer Network (NCCN) risk classification. Cox Proportional Hazards Model analysis was done for risk predictor identification. The median age was 71 years old. Five-year overall and prostate-cancer-specific survival in prostatic adenocarcinoma patients were 77.52% and 79.65%; 10-year survivals were 62.57% and 68.60%, respectively. Survival was significantly poorer in patients with metastases and non-curative management. T staging and Gleason score by NCCN classification effectively stratified prostatic adenocarcinoma patients into different risk groups. T staging was a significant predictor of survival by COX Proportional Hazard Model. PSA screened patients had a significantly higher percentage diagnosed in early stage. PSA screened prostatic adenocarcinoma patients had a better prognosis in both overall and prostate cancer-specific survivals. This Chinese cohort had a lower overall and prostate cancer survival rate than it is reported in western countries. The incidence of early-stage prostate cancer found in PSA-based mass screening was high and there were significant differences in both overall and prostate cancer-specific survival between the PSA-screened and clinically diagnosed patients.

Comparison of clinical and survival characteristics between prostate cancer patients of PSA-based screening and clinical diagnosis in China

PubMed Central

Xu, Libo; Wang, Jinguo; Guo, Baofeng; Zhang, Haixia; Wang, Kaichen; Wang, Ding; Dai, Chang; Zhang, Ling; Zhao, Xuejian

2018-01-01

Prostate-specific antigen (PSA)-based mass screening remains the most controversial topic in prostate cancer. PSA-based mass screening has not been widely used in China yet. The aim of our study was to evaluate the effect of the PSA-based screening in China. The cohort consisted of 1,012 prostate cancer patients. Data were retrospectively collected and clinical characteristics of the cohorts were investigated. Survival was analyzed for prostatic carcinoma of both PSA screened and clinically diagnosed patients according to clinical characteristics and the National Comprehensive Cancer Network (NCCN) risk classification. Cox Proportional Hazards Model analysis was done for risk predictor identification. The median age was 71 years old. Five-year overall and prostate-cancer-specific survival in prostatic adenocarcinoma patients were 77.52% and 79.65%; 10-year survivals were 62.57% and 68.60%, respectively. Survival was significantly poorer in patients with metastases and non-curative management. T staging and Gleason score by NCCN classification effectively stratified prostatic adenocarcinoma patients into different risk groups. T staging was a significant predictor of survival by COX Proportional Hazard Model. PSA screened patients had a significantly higher percentage diagnosed in early stage. PSA screened prostatic adenocarcinoma patients had a better prognosis in both overall and prostate cancer-specific survivals. This Chinese cohort had a lower overall and prostate cancer survival rate than it is reported in western countries. The incidence of early-stage prostate cancer found in PSA-based mass screening was high and there were significant differences in both overall and prostate cancer-specific survival between the PSA-screened and clinically diagnosed patients. PMID:29416625

CCL11 (Eotaxin-1): A New Diagnostic Serum Marker for Prostate Cancer

PubMed Central

Agarwal, Manisha; He, Chang; Siddiqui, Javed; Wei, John; Macoska, Jill A.

2012-01-01

Background The recent recommendation of the U.S. Preventive Services Task Force against PSA-based screening for prostate cancer was based, in part, on the lack of demonstrated diagnostic utility of serum PSA values in the low, but detectable range to successfully predict prostate cancer. Though controversial, this recommendation reinforced the critical need to develop, validate, and determine the utility of other serum and/or urine transcript and protein markers as diagnostic markers for PCa. The studies described here were intended to determine whether inflammatory cytokines might augment serum PSA as a diagnostic marker for prostate cancer. Methods Multiplex ELISA assays were performed to quantify CCL1, CCL2, CCL5, CCL8, CCL11, CCL17, CXCL1, CXCL5, CXCL8, CXCL10, CXCL12, and IL-6 protein levels in the serum of 272 men demonstrating serum PSA values of < 10 ng/ml and undergoing a 12 core diagnostic needle biopsy for detection of prostate cancer. Logistic regression was used to identify the associations between specific chemokines and prostate cancer status adjusted for prostate volume, and baseline PSA. Results Serum levels for CCL1 (I-309) were significantly elevated among all men with enlarged prostates (p<.04). Serum levels for CCL11 (Eotaxin-1) were significantly elevated among men with prostate cancer regardless of prostate size (p<.01). The remaining 10 cytokines examined in this study did not exhibit significant correlations with either prostate volume or cancer status. Conclusions Serum CCL11 values may provide a useful diagnostic tool to help distinguish between prostatic enlargement and prostate cancer among men demonstrating low, but detectable, serum PSA values. PMID:23059958

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.

AZD1152-HQPA induces growth arrest and apoptosis in androgen-dependent prostate cancer cell line (LNCaP) via producing aneugenic micronuclei and polyploidy.

PubMed

Zekri, Ali; Ghaffari, Seyed H; Ghanizadeh-Vesali, Samad; Yaghmaie, Marjan; Salmaninejad, Arash; Alimoghaddam, Kamran; Modarressi, Mohammad H; Ghavamzadeh, Ardeshir

2015-02-01

Prostate cancer is the frequent non-cutaneous tumor with high mortality in men. Prostate tumors contain cells with different status of androgen receptor. Androgen receptor plays important roles in progression and treatment of prostate cancer. Aurora B kinase, with oncogenic potential, is involved in chromosome segregation and cytokinesis, and its inhibition is a promising anti-cancer therapy. In the present study, we aimed to investigate the effects of Aurora B inhibitor, AZD1152-HQPA, on survival and proliferation of androgen receptor (AR)-positive prostate cancer cells. LNCaP was used as androgen-dependent prostate cancer cell line. We explored the effects of AZD1152-HQPA on cell viability, DNA content, micronuclei formation, and expression of genes involved in apoptosis and cell cycle. Moreover, the expression of Aurora B and AR were investigated in 23 benign prostatic hyperplasia and 38 prostate cancer specimens. AZD1152-HQPA treatment induced defective cell survival, polyploidy, and cell death in LNCaP cell line. Centromeric labeling with fluorescence in situ hybridization (FISH) showed that the loss of whole chromosomes is the origin of micronuclei, indicating on aneugenic action of AZD1152-HQPA. Treatment of AZD1152-HQPA decreased expression of AR. Moreover, we found weak positive correlations between the expression of Aurora B and AR in both benign prostatic hyperplasia and prostate cancer specimens (r = 0.25, r = 0.41). This is the first time to show that AZD1152-HQPA can be a useful therapeutic strategy for the treatment of androgen-dependent prostate cancer cell line. AZD1152-HQPA induces aneugenic mechanism of micronuclei production. Taken together, this study provides new insight into the direction to overcome the therapeutic impediments against prostate cancer.

Characterization of SV-40 Tag rats as a model to study prostate cancer

PubMed Central

2009-01-01

Background Prostate cancer is the second most frequently diagnosed cancer in men. Animal models that closely mimic clinical disease in humans are invaluable tools in the fight against prostate cancer. Recently, a Simian Virus-40 T-antigen (SV-40 Tag) targeted probasin promoter rat model was developed. This model, however, has not been extensively characterized; hence we have investigated the ontogeny of prostate cancer and determined the role of sex steroid receptor and insulin-like growth factor-1 (IGF-1) signaling proteins in the novel SV-40 Tag rat. Methods The SV-40 Tag rat was histopathologically characterized for time to tumor development, incidence and multiplicity and in the ventral, dorsal, lateral and anterior lobes of the prostate. Immunoassay techniques were employed to measure cell proliferation, apoptosis, and sex steroid receptor and growth factor signaling-related proteins. Steroid hormone concentrations were measured via coated well enzyme linked immunosorbent assay (ELISA) kits. Results Prostatic intraepithelial neoplasia (PIN) and well-differentiated prostate cancer developed as early as 2 and 10 weeks of age, respectively in the ventral prostate (VP) followed by in the dorsolateral (DLP). At 8 weeks of age, testosterone and dihydrotestosterone (DHT) concentrations in SV-40 Tag rats were increased when compared to non-transgenic rats. High cell proliferation and apoptotic indices were found in VP and DLP of transgenic rats. Furthermore, we observed increased protein expression of androgen receptor, IGF-1, IGF-1 receptor, and extracellular signal-regulated kinases in the prostates of SV-40 Tag rats. Conclusion The rapid development of PIN and prostate cancer in conjunction with the large prostate size makes the SV-40 Tag rat a useful model for studying prostate cancer. This study provides evidence of the role of sex steroid and growth factor proteins in prostate cancer development and defines appropriate windows of opportunity for preclinical trials and aids in the rational design of chemoprevention, intervention, regression, and therapeutic studies using prostate cancer rodent models. PMID:19171036

FOXP3+ regulatory T cells in normal prostate tissue, postatrophic hyperplasia, prostatic intraepithelial neoplasia, and tumor histological lesions in men with and without prostate cancer.

PubMed

Davidsson, Sabina; Andren, Ove; Ohlson, Anna-Lena; Carlsson, Jessica; Andersson, Swen-Olof; Giunchi, Francesca; Rider, Jennifer R; Fiorentino, Michelangelo

2018-01-01

The tumor promoting or counteracting effects of the immune response to cancer development are thought to be mediated to some extent by the infiltration of regulatory T cells (T regs ). In the present study we evaluated the prevalence of T reg populations in stromal and epithelial compartments of normal, post atrophic hyperplasia (PAH), prostatic intraepithelial neoplasia (PIN), and tumor lesions in men with and without prostate cancer. Study subjects were 102 men consecutively diagnosed with localized prostate cancer undergoing radical prostatectomy and 38 men diagnosed with bladder cancer undergoing cystoprostatectomy without prostate cancer at the pathological examination. Whole mount sections from all patients were evaluated for the epithelial and stromal expression of CD4 + T regs and CD8 + T regs in normal, PAH, PIN, and tumor lesions. A Friedmańs test was used to investigate differences in the mean number of T regs across histological lesions. Logistic regression was used to estimate crude and adjusted odds ratios (OR) for prostate cancer for each histological area. In men with prostate cancer, similarly high numbers of stromal CD4 + T regs were identified in PAH and tumor, but CD4 + T regs were less common in PIN. Greater numbers of epithelial CD4+ T regs in normal prostatic tissue were positively associated with both Gleason score and pT-stage. We observed a fourfold increased risk of prostate cancer in men with epithelial CD4 + T regs in the normal prostatic tissue counterpart. Our results may suggest a possible pathway through which PAH develops directly into prostate cancer in the presence of CD4 + T regs and indicate that transformation of the anti-tumor immune response may be initiated even before the primary tumor is established. © 2017 The Authors. The Prostate Published by Wiley Periodicals Inc.

Worldwide Prevalence of Human Papillomavirus and Relative Risk of Prostate Cancer: A Meta-analysis

PubMed Central

Yang, Lin; Xie, Shuanghua; Feng, Xiaoshuang; Chen, Yuheng; Zheng, Tongzhang; Dai, Min; Ke Zhou, Cindy; Hu, Zhibin; Li, Ni; Hang, Dong

2015-01-01

Despite the increasing number of studies conducted recently to evaluate the association between HPV infections and the risk of prostate cancer, the results remain inconclusive. Furthermore, the prevalence and distribution of overall and individual HPV types worldwide in prostate cancer has not been reported until now. Therefore, we estimated the prevalence of HPV in prostate cancer by pooling data of 46 studies with 4919 prostate cancer cases, taking into account the heterogeneity of major related parameters, including study region, specimen type, HPV DNA source, detection method, publication calendar period and Gleason score. Moreover, we tested the association of HPV infections with prostate cancer risks by a meta-analysis of 26 tissue-based case-control studies. We found that the prevalence of HPV infection was 18.93% (95% CI = 17.84–20.05%) in prostate cancer cases, and most of which were high-risk HPV types (17.73%, 95% CI = 16.52–18.99%). The prevalence varied by region, PCR primers used, publication calendar period and Gleason score. Our study also showed a significantly increased risk of prostate cancer with the positivity of overall HPV detected in prostate tissues (OR = 1.79, 95% CI = 1.29–2.49) and revealed the geographic variation of association strength (P < 0.001). In conclusion, HPV infections may contribute to the risk of prostate cancer. PMID:26441160

Raman spectroscopy for prostate cancer detection and characterization (Conference Presentation)

NASA Astrophysics Data System (ADS)

Aubertin, Kelly; Trinh, Quoc-Huy; Jermyn, Michael; St-Pierre, Catherine; Vladoiu, Maria-Claudia; Grosset, Andrée.-Anne; Saad, Fred; Trudel, Dominique; Leblond, Frédéric

2017-02-01

Prostate cancer is the most frequent diagnosed cancers among men. When prostate cancer occurs, the cancer does not result in only one or few localized malignant tumor, but is generally spread within the whole prostate. In order to counteract the very high level of heterogeneities exhibited by prostate tissues, we developed a method for high-resolution co-registration of Raman spectroscopy with prostate cancer diagnosis. Raman spectra were acquired on fresh ex vivo prostate within 2 hours after radical prostatectomy using a multi-wavelength hand-held contact probe. After the measurements, the prostate was reintegrated to the usual pathological workflow: formalin fixated and paraffin embedded (FFPE), and prepared for microscope histopathological analyses. The precise reconstruction of the prostate slice with hematoxylin and eosin (H and E) tissue allows the spatial correlation of the measured area (0.2 mm2) with the correspondent histopathological information, for point-by-point diagnosis determination. The tissue was classified into groups (normal/cancer) and subgroups according to the percentage of benign glands, stroma or cancer. Different machine learning algorithms were tested to classify the spectra with increasing levels of categorization. Preliminary results showed that Raman spectroscopy is capable of detecting prostate cancer with an accuracy >90%. In addition, high percentages of stroma (vs. glands) have been correlated with spectral signature of collagen, which is the main constituent of extracellular matrix.

Use of shear waves for diagnosis and ablation monitoring of prostate cancer: a feasibility study

NASA Astrophysics Data System (ADS)

Gomez, A.; Rus, G.; Saffari, N.

2016-01-01

Prostate cancer remains as a major healthcare issue. Limitations in current diagnosis and treatment monitoring techniques imply that there is still a need for improvements. The efficacy of prostate cancer diagnosis is still low, generating under and over diagnoses. High intensity focused ultrasound ablation is an emerging treatment modality, which enables the noninvasive ablation of pathogenic tissue. Clinical trials are being carried out to evaluate its longterm efficacy as a focal treatment for prostate cancer. Successful treatment of prostate cancer using non-invasive modalities is critically dependent on accurate diagnostic means and is greatly benefited by a real-time monitoring system. While magnetic resonance imaging remains the gold standard for prostate imaging, its wider implementation for prostate cancer diagnosis remains prohibitively expensive. Conventional ultrasound is currently limited to guiding biopsy. Elastography techniques are emerging as a promising real-time imaging method, as cancer nodules are usually stiffer than adjacent healthy prostatic tissue. In this paper, a new transurethral approach is proposed, using shear waves for diagnosis and ablation monitoring of prostate cancer. A finite-difference time domain model is developed for studying the feasibility of the method, and an inverse problem technique based on genetic algorithms is proposed for reconstructing the location, size and stiffness parameters of the tumour. Preliminary results indicate that the use of shear waves for diagnosis and monitoring ablation of prostate cancer is feasible.

Ultrasound elastography of the prostate: state of the art.

PubMed

Correas, J-M; Tissier, A-M; Khairoune, A; Khoury, G; Eiss, D; Hélénon, O

2013-05-01

Prostate cancer is the cancer exhibiting the highest incidence rate and it appears as the second cause of cancer death in men, after lung cancer. Prostate cancer is difficult to detect, and the treatment efficacy remains limited despite the increase use of biological tests (prostate-specific antigen [PSA] dosage), the development of new imaging modalities, and the use of invasive procedures such as biopsy. Ultrasound elastography is a novel imaging technique capable of mapping tissue stiffness of the prostate. It is known that prostatic cancer tissue is often harder than healthy tissue (information used by digital rectal examination [DRE]). Two elastography techniques have been developed based on different principles: first, quasi-static (or strain) technique, and second, shear wave technique. The tissue stiffness information provided by US elastography should improve the detection of prostate cancer and provide guidance for biopsy. Prostate elastography provides high sensitivity for detecting prostate cancer and shows high negative predictive values, ensuring that few cancers will be missed. US elastography should become an additional method of imaging the prostate, complementing the conventional transrectal ultrasound and MRI. This technique requires significant training (especially for quasi-static elastography) to become familiar with acquisition process, acquisition technique, characteristics and limitations, and to achieve correct diagnoses. Copyright © 2013 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.

[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.

Prostate ultrasound--for urologists only?

PubMed

Frauscher, Ferdinand; Gradl, Johann; Pallwein, Leo

2005-11-23

The value of ultrasound (US) in the diagnosis of prostate cancer has dramatically increased in the past decade. This is mainly related to the increasing incidence of prostate cancer, the most common cancer in men and one of the most important causes of death from cancer in men. The value of conventional gray-scale US for prostate cancer detection has been extensively investigated, and has shown a low sensitivity and specificity. Therefore conventional gray-scale US is mainly used by urologists for guiding systematic prostate biopsies. With the development of new US techniques, such as color and power Doppler US, and the introduction of US contrast agents, the role of US for prostate cancer detection has dramatically changed. Advances in US techniques were introduced to further increase the value of US contrast agents. Although most of these developments in US techniques, which use the interaction of the contrast agent with the transmitted US waves, are very sensitive for the detection of microbubbles, they are mostly unexplored, in particular for prostate applications. Early reports of contrast-enhanced US investigations of blood flow of the prostate have shown that contrast-enhanced US adds important information to the conventional gray-scale US technique. Furthermore, elastography or 'strain imaging' seems to have great potential in prostate cancer detection. Since these new advances in US are very sophisticated and need a long learning curve, radiologists, who are overall better trained with these new US techniques, will play a more important role in prostate cancer diagnosis. Current trends show that these new US techniques may allow for targeted biopsies and therefore replace the current 'gold standard' for prostate cancer detection--the systematic biopsy. Consequently the use of these new US techniques for the detection and clinical staging of prostate cancer is promising. However, future clinical trials will be needed to determine if the promise of these new US advances of the prostate evolves into clinical application. International Cancer Imaging Society.

A Model for Understanding the Genetic Basis for Disparity in Prostate Cancer Risk

DTIC Science & Technology

2016-10-01

patterns were observed for association with dietary factors or life style factors such as physical activity, occupational history, sexual behavior...The resultant differentiated cells are cultured in prostate epithelial cell growth medium (PrEGM) and stromal basal medium supplemented with R...Sponding1, Noggin, EGF, 1X B27 supplement , retinoic acid and dihydrotestosterone. BOTTOM: Preliminary iPSC differentiation into definitive endoderm over

Prostate Cancer Ambassadors: Process and Outcomes of a Prostate Cancer Informed Decision-Making Training Program.

PubMed

Vines, Anissa I; Hunter, Jaimie C; Carlisle, Veronica A; Richmond, Alan N

2016-04-19

African American men bear a higher burden of prostate cancer than Caucasian men, but knowledge about how to make an informed decision about prostate cancer screening is limited. A lay health advisor model was used to train "Prostate Cancer Ambassadors" on prostate cancer risk and symptoms, how to make an informed decision for prostate-specific antigen screening, and how to deliver the information to members of their community. Training consisted of two, 6-hour interactive sessions and was implemented in three predominantly African American communities over an 8-month period between 2013 and 2014. Following training, Ambassadors committed to contacting at least 10 people within 3 months using a toolkit composed of wallet-sized informational cards for distribution, a slide presentation, and a flip chart. Thirty-two Ambassadors were trained, with more than half being females (59%) and half reporting a family history of prostate cancer. Prostate cancer knowledge improved significantly among Ambassadors (p≤ .0001). Self-efficacy improved significantly for performing outreach tasks (p< .0001), and among women in helping a loved one with making an informed decision (p= .005). There was also an improvement in collective efficacy in team members (p= .0003). Twenty-nine of the Ambassadors fulfilled their commitment to reach at least 10 people (average number of contacts per Ambassador was 11). In total, 355 individuals were reached with the prostate cancer information. The Ambassador training program proved successful in training Ambassadors to reach communities about prostate cancer and how to make an informed decision about screening. © The Author(s) 2016.

Relative value of race, family history and prostate specific antigen as indications for early initiation of prostate cancer screening.

PubMed

Vertosick, Emily A; Poon, Bing Ying; Vickers, Andrew J

2014-09-01

Many guidelines suggest earlier screening for prostate cancer in men at high risk, with risk defined in terms of race and family history. Recent evidence suggests that baseline prostate specific antigen is strongly predictive of the long-term risk of aggressive prostate cancer. We compared the usefulness of risk stratifying early screening by race, family history and prostate specific antigen at age 45 years. Using estimates from the literature we calculated the proportion of men targeted for early screening using family history, black race or prostate specific antigen as the criterion for high risk. We calculated the proportion of prostate cancer deaths that would occur in those men by age 75 years. Screening based on family history involved 10% of men, accounting for 14% of prostate cancer deaths. Using black race as a risk criterion involved 13% of men, accounting for 28% of deaths. In contrast, 44% of prostate cancer deaths occurred in the 10% of men with the highest prostate specific antigen at age 45 years. In no sensitivity analysis for race and family history did the ratio of risk group size to number of prostate cancer deaths in that risk group approach that of prostate specific antigen. Basing decisions for early screening on prostate specific antigen at age 45 years provided the best ratio between men screened and potential cancer deaths avoided. Given the lack of evidence that race or family history affects the relationship between prostate specific antigen and risk, prostate specific antigen based risk stratification would likely include any black men or men with a family history who are destined to experience aggressive disease. Differential screening based on risk should be informed by baseline prostate specific antigen. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Prostate cancer involving bilateral seminal vesicles along with bone and testicular metastases: a case report.

PubMed

Gao, Qingqiang; Chen, Jianhuai; Dai, Yutian

2018-03-09

In the past 20 years, the incidence of prostate cancer has risen rapidly. It has been ranked as the third most common malignant tumor of the male genitourinary system. Testicular metastasis is uncommon in prostate cancer. Most cases are incidentally found in the treatment of prostate cancer with orchiectomy. Therefore, we believed it was necessary to report the case of our patient with this disease. We present a case of a 69-year-old Han Chinese man with a high total prostate-specific antigen level. A transrectal ultrasound-guided prostate biopsy was performed. A pathology report showed prostate cancer tissue with a Gleason score of 4 + 4 = 8/10. Imaging findings suggested that the prostate cancer tissue involved bilateral seminal vesicles and multiple bones. Next, radioactive seed implantation was carried out, and endocrine therapy was continued after the operation. Then enlargement of the left scrotum was found along with a total prostate-specific antigen level of 19.21 ng/ml. Computed tomography of the middle abdomen and pelvic cavity revealed 2.0 × 1.3-cm lesions of the left testis. The patient underwent a left testicular high resection and right orchiectomy. The postoperative pathology report showed metastatic prostate cancer cells in the left testis. Testicular metastasis of prostate cancer is rare. Therefore, a testicular physical examination is necessary for patients without relapse to avoid a missed diagnosis. Testicular metastasis should be treated according to the principle of treatment for advanced prostate adenocarcinoma if testicular metastasis of prostate adenocarcinoma is detected.

Expression of the cancer-testis antigen BORIS correlates with prostate cancer.

PubMed

Cheema, Zubair; Hari-Gupta, Yukti; Kita, Georgia-Xanthi; Farrar, Dawn; Seddon, Ian; Corr, John; Klenova, Elena

2014-02-01

BORIS, a paralogue of the transcription factor CTCF, is a member of the cancer-testis antigen (CT) family. BORIS is normally present at high levels in the testis; however it is aberrantly expressed in various tumors and cancer cell lines. The main objectives of this study were to investigate BORIS expression together with sub-cellular localization in both prostate cell lines and tumor tissues, and assess correlations between BORIS and clinical/pathological characteristics. We examined BORIS mRNA expression, protein levels and cellular localization in a panel of human prostate tissues, cancer and benign, together with a panel prostate cell lines. We also compared BORIS levels and localization with clinical/pathological characteristics in prostate tumors. BORIS was detected in all inspected prostate cancer cell lines and tumors, but was absent in benign prostatic hyperplasia. Increased levels of BORIS protein positively correlated with Gleason score, T-stage and androgen receptor (AR) protein levels in prostate tumors. The relationship between BORIS and AR was further highlighted in prostate cell lines by the ability of ectopically expressed BORIS to activate the endogenous AR mRNA and protein. BORIS localization in the nucleus plus cytoplasm was also associated with higher BORIS levels and Gleason score. Detection of BORIS in prostate tumors suggests potential applications of BORIS as a biomarker for prostate cancer diagnosis, as an immunotherapy target and, potentially, a prognostic marker of more aggressive prostate cancer. The ability of BORIS to activate the AR gene indicates BORIS involvement in the growth and development of prostate tumors. © 2013 Wiley Periodicals, Inc.

San Antonio Center of Biomarkers of Risk for Prostate Cancer (SABOR) — EDRN Public Portal

Cancer.gov

To determine if there are ways to predict which men will get prostate cancer, if there are ways to predict how a prostate cancer will develop (for example, slow or rapid growth) and why there are differences in prostate cancer among men from different ethnic backgrounds.

3 CFR 9010 - Proclamation 9010 of August 30, 2013. National Prostate Cancer Awareness Month, 2013

Code of Federal Regulations, 2014 CFR

2014-01-01

... Prostate Cancer Awareness Month, 2013 9010 Proclamation 9010 Presidential Documents Proclamations Proclamation 9010 of August 30, 2013 Proc. 9010 National Prostate Cancer Awareness Month, 2013By the President of the United States of America A Proclamation Among American men, prostate cancer is both the second...

Counseling the Client with Prostate Cancer.

ERIC Educational Resources Information Center

Curtis, Russell C.; Juhnke, Gerald A.

2003-01-01

Prostate cancer is prevalent in the United States and has a far-reaching effect on men and their relationships. Being diagnosed with and treated for prostate cancer often causes men to experience side effects that induce physical, emotional, and social change. Counselors need to be aware of prostate cancer's impact on men and their families.…

CHEK2 (∗) 1100delC Mutation and Risk of Prostate Cancer.

PubMed

Hale, Victoria; Weischer, Maren; Park, Jong Y

2014-01-01

Although the causes of prostate cancer are largely unknown, previous studies support the role of genetic factors in the development of prostate cancer. CHEK2 plays a critical role in DNA replication by responding to double-stranded breaks. In this review, we provide an overview of the current knowledge of the role of a genetic variant, 1100delC, of CHEK2 on prostate cancer risk and discuss the implication for potential translation of this knowledge into clinical practice. Currently, twelve articles that discussed CHEK2 (∗)1100delC and its association with prostate cancer were identified. Of the twelve prostate cancer studies, five studies had independent data to draw conclusive evidence from. The pooled results of OR and 95% CI were 1.98 (1.23-3.18) for unselected cases and 3.39 (1.78-6.47) for familial cases, indicating that CHEK2 (∗)1100delC mutation is associated with increased risk of prostate cancer. Screening for CHEK2(∗)1100delC should be considered in men with a familial history of prostate cancer.

CHEK2 ∗1100delC Mutation and Risk of Prostate Cancer

PubMed Central

Park, Jong Y.

2014-01-01

Although the causes of prostate cancer are largely unknown, previous studies support the role of genetic factors in the development of prostate cancer. CHEK2 plays a critical role in DNA replication by responding to double-stranded breaks. In this review, we provide an overview of the current knowledge of the role of a genetic variant, 1100delC, of CHEK2 on prostate cancer risk and discuss the implication for potential translation of this knowledge into clinical practice. Currently, twelve articles that discussed CHEK2 ∗1100delC and its association with prostate cancer were identified. Of the twelve prostate cancer studies, five studies had independent data to draw conclusive evidence from. The pooled results of OR and 95% CI were 1.98 (1.23–3.18) for unselected cases and 3.39 (1.78–6.47) for familial cases, indicating that CHEK2 ∗1100delC mutation is associated with increased risk of prostate cancer. Screening for CHEK2∗1100delC should be considered in men with a familial history of prostate cancer. PMID:25431674

Plasma cell-free DNA and its DNA integrity as biomarker to distinguish prostate cancer from benign prostatic hyperplasia in patients with increased serum prostate-specific antigen.

PubMed

Feng, Jiang; Gang, Feng; Li, Xiao; Jin, Tang; Houbao, Huang; Yu, Cao; Guorong, Li

2013-08-01

To investigate whether plasma cell-free DNA (cfDNA) or its integrity could differentiate prostate cancer from benign prostate hyperplasia (BPH) in patients with serum prostate-specific antigen (PSA) ≥ 4 ng/ml. Ninety-six patients with prostate cancer and 112 patients with BPH were enrolled. cfDNA levels in plasma before prostate biopsy were quantified by real-time PCR amplification of ALU gene (product size of 115 bp), and quantitative ratio of ALU (247 bp) to ALU (115 bp) reflected the integrity of cfDNA. In patients with serum PSA ≥ 4 ng/ml, there were significant differences in plasma cfDNA or its integrity between the patients with prostate cancer (19.74 ± 4.43, 0.34 ± 0.05) and patients with BPH (7.36 ± 1.58, 0.19 ± 0.03; P < 0.001, P < 0.001). Prostate cancer could be differentiated with a sensitivity of 73.2 % and a specificity of 72.7 % by cfDNA (AUC = 0.864). The integrity of cfDNA had a sensitivity of 81.7 % and a specificity of 78.8 % for the distinguishing prostate cancer from BPH (AUC = 0.910). cfDNA and its integrity could be applied to differentiate prostate cancer from BPH in patients with serum PSA ≥ 4 ng/ml.

Behavioral stress accelerates prostate cancer development in mice

PubMed Central

Hassan, Sazzad; Karpova, Yelena; Baiz, Daniele; Yancey, Dana; Pullikuth, Ashok; Flores, Anabel; Register, Thomas; Cline, J. Mark; D’Agostino, Ralph; Danial, Nika; Datta, Sandeep Robert; Kulik, George

2013-01-01

Prostate cancer patients have increased levels of stress and anxiety. Conversely, men who take beta blockers, which interfere with signaling from the stress hormones adrenaline and noradrenaline, have a lower incidence of prostate cancer; however, the mechanisms underlying stress–prostate cancer interactions are unknown. Here, we report that stress promotes prostate carcinogenesis in mice in an adrenaline-dependent manner. Behavioral stress inhibited apoptosis and delayed prostate tumor involution both in phosphatase and tensin homolog–deficient (PTEN-deficient) prostate cancer xenografts treated with PI3K inhibitor and in prostate tumors of mice with prostate-restricted expression of c-MYC (Hi-Myc mice) subjected to androgen ablation therapy with bicalutamide. Additionally, stress accelerated prostate cancer development in Hi-Myc mice. The effects of stress were prevented by treatment with the selective β2-adrenergic receptor (ADRB2) antagonist ICI118,551 or by inducible expression of PKA inhibitor (PKI) or of BCL2-associated death promoter (BAD) with a mutated PKA phosphorylation site (BADS112A) in xenograft tumors. Effects of stress were also blocked in Hi-Myc mice expressing phosphorylation-deficient BAD (BAD3SA). These results demonstrate interactions between prostate tumors and the psychosocial environment mediated by activation of an adrenaline/ADRB2/PKA/BAD antiapoptotic signaling pathway. Our findings could be used to identify prostate cancer patients who could benefit from stress reduction or from pharmacological inhibition of stress-induced signaling. PMID:23348742

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.

EphA2 enhances the proliferation and invasion ability of LNCaP prostate cancer cells

PubMed Central

CHEN, PEIJIE; HUANG, YAN; ZHANG, BO; WANG, QIUQUAN; BAI, PEIMING

2014-01-01

EphA2 is persistently overexpressed and functionally changed in numerous human cancers. However, to the best of our knowledge, the role that EphA2 plays in prostate cancer is not entirely clear. To investigate the roles of EphA2 in the development and progression of prostate cancer, the present study initially evaluated the roles of the EphA2 protein in LNCaP prostate cancer cells using recombinant plasmid, western blot analysis, flow cytometry, Matrigel invasion chamber and the cell counting kit-8 assay. An immunohistochemistry assay was also conducted to observe the effects of EphA2 in prostate cancer tissues. The results demonstrated that the LNCaP human prostate cancer cells that were transfected with pcDNA3.1(+) plasmid-mediated pcDNA3.1(+)-EphA2, markedly enhanced the cell growth and invasion in vitro. Additionally, EphA2 was overexpressed in prostate cancer specimens and the expression of EphA2 was significantly associated with Gleason grade, total prostate-specific antigen, advanced clinical stage and lymph node metastasis. Collectively, these results demonstrate that EphA2 is involved in malignant cell behavior and is a potential therapeutic target in human prostate cancer. PMID:24959216

Huntingtin-interacting protein 1 is overexpressed in prostate and colon cancer and is critical for cellular survival.

PubMed

Rao, Dinesh S; Hyun, Teresa S; Kumar, Priti D; Mizukami, Ikuko F; Rubin, Mark A; Lucas, Peter C; Sanda, Martin G; Ross, Theodora S

2002-08-01

Huntingtin-interacting protein 1 (HIP1) is a cofactor in clathrin-mediated vesicle trafficking. It was first implicated in cancer biology as part of a chromosomal translocation in leukemia. Here we report that HIP1 is expressed in prostate and colon tumor cells, but not in corresponding benign epithelia. The relationship between HIP1 expression in primary prostate cancer and clinical outcomes was evaluated with tissue microarrays. HIP1 expression was significantly associated with prostate cancer progression and metastasis. Conversely, primary prostate cancers lacking HIP1 expression consistently showed no progression after radical prostatectomy. In addition, the expression of HIP1 was elevated in prostate tumors from the transgenic mouse model of prostate cancer (TRAMP). At the molecular level, expression of a dominant negative mutant of HIP1 led to caspase-9-dependent apoptosis, suggesting that HIP1 is a cellular survival factor. Thus, HIP1 may play a role in tumorigenesis by allowing the survival of precancerous or cancerous cells. HIP1 might accomplish this via regulation of clathrin-mediated trafficking, a fundamental cellular pathway that has not previously been associated with tumorigenesis. HIP1 represents a putative prognostic factor for prostate cancer and a potential therapy target in prostate as well as colon cancers.

Huntingtin-interacting protein 1 is overexpressed in prostate and colon cancer and is critical for cellular survival

PubMed Central

Rao, Dinesh S.; Hyun, Teresa S.; Kumar, Priti D.; Mizukami, Ikuko F.; Rubin, Mark A.; Lucas, Peter C.; Sanda, Martin G.; Ross, Theodora S.

2002-01-01

Huntingtin-interacting protein 1 (HIP1) is a cofactor in clathrin-mediated vesicle trafficking. It was first implicated in cancer biology as part of a chromosomal translocation in leukemia. Here we report that HIP1 is expressed in prostate and colon tumor cells, but not in corresponding benign epithelia. The relationship between HIP1 expression in primary prostate cancer and clinical outcomes was evaluated with tissue microarrays. HIP1 expression was significantly associated with prostate cancer progression and metastasis. Conversely, primary prostate cancers lacking HIP1 expression consistently showed no progression after radical prostatectomy. In addition, the expression of HIP1 was elevated in prostate tumors from the transgenic mouse model of prostate cancer (TRAMP). At the molecular level, expression of a dominant negative mutant of HIP1 led to caspase-9–dependent apoptosis, suggesting that HIP1 is a cellular survival factor. Thus, HIP1 may play a role in tumorigenesis by allowing the survival of precancerous or cancerous cells. HIP1 might accomplish this via regulation of clathrin-mediated trafficking, a fundamental cellular pathway that has not previously been associated with tumorigenesis. HIP1 represents a putative prognostic factor for prostate cancer and a potential therapy target in prostate as well as colon cancers. PMID:12163454

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.

Integrative analysis identifies targetable CREB1/FoxA1 transcriptional co-regulation as a predictor of prostate cancer recurrence.

PubMed

Sunkel, Benjamin; Wu, Dayong; Chen, Zhong; Wang, Chiou-Miin; Liu, Xiangtao; Ye, Zhenqing; Horning, Aaron M; Liu, Joseph; Mahalingam, Devalingam; Lopez-Nicora, Horacio; Lin, Chun-Lin; Goodfellow, Paul J; Clinton, Steven K; Jin, Victor X; Chen, Chun-Liang; Huang, Tim H-M; Wang, Qianben

2016-05-19

Identifying prostate cancer-driving transcription factors (TFs) in addition to the androgen receptor promises to improve our ability to effectively diagnose and treat this disease. We employed an integrative genomics analysis of master TFs CREB1 and FoxA1 in androgen-dependent prostate cancer (ADPC) and castration-resistant prostate cancer (CRPC) cell lines, primary prostate cancer tissues and circulating tumor cells (CTCs) to investigate their role in defining prostate cancer gene expression profiles. Combining genome-wide binding site and gene expression profiles we define CREB1 as a critical driver of pro-survival, cell cycle and metabolic transcription programs. We show that CREB1 and FoxA1 co-localize and mutually influence each other's binding to define disease-driving transcription profiles associated with advanced prostate cancer. Gene expression analysis in human prostate cancer samples found that CREB1/FoxA1 target gene panels predict prostate cancer recurrence. Finally, we showed that this signaling pathway is sensitive to compounds that inhibit the transcription co-regulatory factor MED1. These findings not only reveal a novel, global transcriptional co-regulatory function of CREB1 and FoxA1, but also suggest CREB1/FoxA1 signaling is a targetable driver of prostate cancer progression and serves as a biomarker of poor clinical outcomes. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Concurrent Hepsin overexpression and adenomatous polyposis coli deletion causes invasive prostate carcinoma in mice.

PubMed

Valkenburg, Kenneth C; Hostetter, Galen; Williams, Bart O

2015-10-01

A clinical need to better categorize patients with prostate cancer exists. The Wnt/β-catenin signaling pathway plays important roles in human prostate cancer progression. Deletion of the endogenous Wnt antagonist adenomatous polyposis coli (Apc) in mice causes high grade prostate intraepithelial neoplasia, widely thought to be the precursor to prostate cancer. However, no metastasis occurrs in this model. New mouse models are needed to determine molecular causes of tumorigenesis, progression, and metastasis. To determine whether the overexpression of the prostate oncogene Hepsin could cause prostate cancer progression, we crossed a prostate-specific Hepsin overexpression model to a prostate-specific Apc-deletion model and classified the observed phenotype. When Apc was deleted and Hepsin overexpressed concurrently, mice displayed invasive carcinoma, with loss of membrane characteristics and increase of fibrosis. These tumors had both luminal and basaloid characteristics. Though no metastasis was observed, there was evidence of adenomas and lung necrosis, inflammation, and chronic hemorrhage. This work indicates that the Wnt/β-catenin pathway and the Hepsin pathway act in concert to promote prostate cancer progression. Both of these pathways are up-regulated in human prostate cancer and could represent chemotherapeutic targets. © 2015 Wiley Periodicals, Inc.