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Histopathology 2019 Feb 28. Epub 2019 Feb 28.

Department of Pathology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.

Aims: Many glandular lesions can mimic prostate cancer microscopically, including atrophic glands, adenosis and prostatic intraepithelial neoplasia. While the characteristic histopathological and immunohistochemical features of these lesions have been well established, little is known about their three-dimensional architecture. Our objective was to evaluate the three-dimensional organisation of common prostate epithelial lesions. Read More

Invest Radiol 2019 Mar;54(3):146-152

From the Department of Radiology, University Hospital Jena, Jena, Germany.

Objectives: The aim of the study was to determine the quantitative T2 values in prostate tissue and evaluate them for detection and grading of prostate cancer.

Materials And Methods: After approval from the local ethics committee, morphological T2-weighted (T2w) images, apparent diffusion coefficient (ADC) maps from diffusion-weighted images, quantitative T2 maps, and calculated T2w images from 75 men (median age, 66.3 years; median PSA, 8. Read More

Exp Oncol 2017 Dec;39(4):269-275

School of Psychology, University of Ottawa, Ottawa K1N 6N5, ON, Canada.

Puberty can be a critical period for the long-term development of diseases, especially for stress-related disorders that depend on neuroendocrine and immune responses. Some organs like the prostate are prone to diseases that result from neuroendocrine or immune challenges, such as cancer.

Aim: In the present study, we assessed the long-term effects of an acute pubertal stressor (immune-challenge) on the development of precancerous lesions in adult rats, and compared them with testosterone-induced prostatic lesions. Read More

Arkh Patol 2017;79(2):10-14

Russian Medical Academy of Postgraduate Education, Ministry of Health of Russia, Moscow, Russia.

The differential diagnosis of benign and malignant changes in the prostate presents still definite difficulties; the antibody panel existing for these purposes is imperfect. Fatty acid synthase (FASN) is an androgen-regulated enzyme required for de novo lipogenesis. A number of studies have noted increased expression of the gene encoding this protein in tumors and precancerous lesions of different locations. Read More

Exp Oncol 2016 Jun;38(2):73-9

Center for Brain Research, University of Veracruz, Xalapa, Veracruz 91190, Mexico.

Unlabelled: The prostate is an exocrine reproductive gland that participates in ejaculation and it is prone to diseases, including cancer.

Aim: In the pre-sent study, we assessed the long-term effects of copulation on the development of precancerous lesions in rats, and compared them with testosterone-induced prostatic lesions.

Materials And Methods: One group of Wistar males was given 10 copulatory sessions to one ejaculation with ovariectomized, hormone-primed females. Read More

Hum Pathol 2016 09 14;55:117-25. Epub 2016 May 14.

Pathology, Johns Hopkins School of Medicine, Baltimore, MD 21231; Oncology, Johns Hopkins School of Medicine, Baltimore, MD 21231. Electronic address:

High-grade prostatic intraepithelial neoplasia (HGPIN) is widely believed to represent a precursor to invasive prostatic adenocarcinoma. However, recent molecular studies have suggested that retrograde spread of invasive adenocarcinoma into pre-existing prostatic ducts can morphologically mimic HGPIN. Thus, previous molecular studies characterizing morphologically identified HGPIN occurring in radical prostatectomies or needle biopsies with concurrent invasive carcinoma may be partially confounded by intraductal spread of invasive tumor. Read More

Mol Cell Endocrinol 2016 07 7;430:125-37. Epub 2016 Apr 7.

ETH Zurich, Animal Physiology, Institute of Agricultural Sciences, Zurich, Switzerland; Technische Universität München, Physiology Weihenstephan, Freising, Germany. Electronic address:

There is growing evidence that early life exposure to endocrine disrupting chemicals might increase the risk for certain adult onset diseases, in particular reproductive health problems and hormone dependent cancers. Studies in rodents suggest that perinatal exposure to even low doses of estrogenic substances can cause adverse effects, including epigenetic reprogramming of the prostate and increased formation of precancerous lesions. We analyzed the effects of an in utero exposure to the strongest natural estrogen, estradiol-17β, in a pig model. Read More

Cancer Prev Res (Phila) 2016 Jan 28;9(1):35-42. Epub 2015 Oct 28.

Hormel Institute, University of Minnesota, Austin, Minnesota.

Monomethylated selenium (MM-Se) forms that are precursors of methylselenol, such as methylseleninic acid (MSeA), differ in metabolism and anticancer activities in preclinical cell and animal models from seleno-methionine that had failed to exert preventive efficacy against prostate cancer in North American men. Given that human prostate cancer arises from precancerous lesions such as high-grade prostatic intraepithelial neoplasia (HG-PIN), which frequently have lost phosphatase and tensin homolog (PTEN) tumor suppressor permitting phosphatidylinositol-3-OH kinase (PI3K)-protein kinase B (AKT) oncogenic signaling, we tested the efficacy of MSeA to inhibit HG-PIN progression in Pten prostate-specific knockout (KO) mice and assessed the mechanistic involvement of p53-mediated cellular senescence and of the androgen receptor (AR). We observed that short-term (4 weeks) oral MSeA treatment significantly increased expression of P53 and P21Cip1 proteins and senescence-associated-β-galactosidase staining, and reduced Ki67 cell proliferation index in Pten KO prostate epithelium. Read More

Cancer Prev Res (Phila) 2015 Aug 19;8(8):683-92. Epub 2015 May 19.

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, Maryland. Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Dietary carcinogens, such as 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), and chronic inflammation have each been implicated as etiologic agents in prostate cancer. We hypothesized that bacterial prostatitis would accelerate PhIP-induced preinvasive lesions in the rat prostate. Male Fischer 344 rats were assigned into 4 groups: Control (untreated), PhIP (200 ppm in the diet for 20 weeks), Escherichia coli (E. Read More

Prostate 2015 Aug 20;75(11):1177-86. Epub 2015 Apr 20.

Department of Scienza e Tecnologia del Farmaco, University of Turin, Turin, Italy.

Background: Antioxidants effectiveness in prostate cancer (PCa) chemoprevention has been severely questioned, especially after the recent results of the Selenium and Vitamin E Cancer Prevention Trial. We present the results of a double-blind randomized controlled trial (dbRCT) on the pharmacokinetic, clinical, and molecular activity of dietary supplements containing lycopene, selenium, and green tea catechins (GTCs) in men with multifocal high grade prostatic intraepithelial neoplasia (mHGPIN) and/or atypical small acinar proliferation (ASAP).

Methods: From 2009 to 2014, we conducted a dbRCT including 60 patients with primary mHGPIN and/or ASAP receiving daily lycopene 35 mg, selenium 55 µg, and GTCs 600 mg, or placebo for 6 months. Read More

Exp Oncol 2015 Mar;37(1):13-8

Center for Brain Research, University of Veracruz, Xalapa, Ver. 91190, Mexico.

Unlabelled: Evidence indicates that prolactin plays a crucial role in the normal function and development of the prostate, but abnormal high levels of the hormone are associated with hyperplasia and cancer of the gland.

Aims: The present study was designed to describe the progressive specific histological abnormalities in the prostate of rats with chronic hyperprolactinemia.

Material And Methods: Prolactin was administered during 4; 12 or 24 weeks, and the resulting prostatic alterations were compared with control rats, and also with those treated with testosterone, or the combination of prolactin + testosterone. Read More

Lab Invest 2015 May 23;95(5):546-60. Epub 2015 Feb 23.

1] Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OH, USA [2] Center for Environmental Genetics, University of Cincinnati College of Medicine, Cincinnati, OH, USA [3] Cincinnati Cancer Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA [4] Cincinnati Veteran Affairs Hospital Medical Center, Cincinnati, OH, USA.

Disorders of the prostate and lower urinary tract are common in elderly men. We investigated the role of metallothionein-1 (MT1) in prostate carcinogenesis by generating a prostate-specific, MT1-expressing mouse. Unexpectedly, genomic analyses revealed that a 12. Read More

Prostate 2015 Feb 18;75(2):126-40. Epub 2014 Oct 18.

Division of Toxicology and Risk Assessment, National Food Institute, Technical University of Denmark, Søborg, Denmark.

Background: Elevated levels of endogenous or exogenous estrogens during fetal life can induce permanent disturbances in prostate growth and predispose to precancerous lesions. Recent studies have indicated that also early anti-androgen exposure may affect prostate cancer risk.

Methods: We examined the influence of perinatal exposure to mixtures of anti-androgenic and estrogenic chemicals on prostate development. Read More

Neoplasia 2014 May 14;16(5):377-89. Epub 2014 Jun 14.

Department of Hematology and Medical Oncology, Emory University School of Medicine, Winship Cancer Institute, Atlanta, GA 30322. Electronic address:

The ATBF1/ZFHX3 gene at 16q22 is the second most frequently mutated gene in human prostate cancer and has reduced expression or mislocalization in several types of human tumors. Nonetheless, the hypothesis that ATBF1 has a tumor suppressor function in prostate cancer has not been tested. In this study, we examined the role of ATBF1 in prostatic carcinogenesis by specifically deleting Atbf1 in mouse prostatic epithelial cells. Read More

Hum Pathol 2014 Aug 12;45(8):1572-81. Epub 2014 Apr 12.

Department of Pathology and Genomic Medicine, Houston, TX, USA; Weill Cornell Medical College of Cornell University, Houston, TX, USA. Electronic address:

Intraductal carcinoma of the prostate (IDC-P) and high-grade prostatic intraepithelial neoplasia (HGPIN) are two distinct intraductal lesions; the former is usually associated with invasive carcinoma and has an aggressive course while the latter is considered a precancerous lesion. In addition, there are morphologically lesions not well characterized that fall between IDC-P and HGPIN, consequently termed "atypical cribriform lesions (ACLs)." Using whole mount radical prostatectomy specimens, we evaluated the relationship between these intraductal proliferative lesions and clinicopathological parameters. Read More

Nutr Cancer 2014 28;66(5):825-34. Epub 2014 Apr 28.

a University of Illinois at Chicago, School of Medicine , Department of Pathology , Chicago , Illinois , USA.

Previous animal studies examining dietary selenium effects on prostatic carcinogenesis did not show preventive benefit, including 1 study in a rat model involving testosterone (T) and estradiol (E2)-induced prostatic oxidative stress. Here, we examined modulation of T + E2-induced prostatic oxidative stress, dysplasia, and inflammation by L-selenomethionine at 1.5 or 3. Read More

PLoS One 2013 4;8(9):e73100. Epub 2013 Sep 4.

German Cancer Research Center (DKFZ), Heidelberg, Germany.

SNPs in the Prostate Stem Cell Antigen (PSCA) gene have been found associated with gastric cancer (GC) risk in a genome-wide association study. This association has been replicated in several populations. In this study we assessed the impact of PSCA genotype on the risk of advanced gastric precancerous lesions and GC. Read More

Hum Pathol 2013 Sep 9;44(9):1895-901. Epub 2013 May 9.

Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD 21231, USA.

Adenosis (atypical adenomatous hyperplasia) is a benign lesion that morphologically mimics prostate adenocarcinoma, although the relationship between these 2 lesions is still debated. The TMPRSS2-ERG fusion is a common chromosomal rearrangement that occurs early in the development of invasive adenocarcinoma of the prostate and results in the expression of a truncated ERG protein. This fusion is present in 50% of adenocarcinomas and in 20% of high-grade prostate intraepithelial lesions. Read More

Pathology 2013 04;45(3):251-63

Division of Anatomical Pathology, Queen Elizabeth II Health Sciences Centre and Department of Pathology, Dalhousie University, Halifax, Nova Scotia.

There are a variety of morphological patterns and processes that have been implicated in the pathogenesis of prostate cancer. Prostatic intraepithelial neoplasia (PIN), inflammation with or without atrophy, and adenosis (atypical adenomatous hyperplasia) have all been given candidate status as precursor lesions of prostatic adenocarcinoma. Based on decades of research, high grade prostatic intraepithelial neoplasia (HPIN), a proliferative lesion of prostatic secretory cells, has emerged as the most likely morphological pre-invasive lesion involved in the evolution of many but not all prostatic adenocarcinomas. Read More

Urology 2013 Feb;81(2):370-5

Department of Urology and Pediatric Urology, University of Schleswig-Holstein, Campus Kiel, Kiel, Germany.

Objective: To define potential improvement in prostate cancer detection by application of a computer-aided, targeted, biopsy regimen using HistoScanning.

Materials And Methods: We analyzed 80 patients who underwent systematic transrectal, targeted transrectal, and targeted perineal biopsies. Each patient was diagnosed preoperatively by HistoScanning, defining a maximum of 3 suspicious areas. Read More

Pathobiology 2013 11;80(3):119-26. Epub 2013 Jan 11.

Department of Pathology, Nara Medical University School of Medicine, Nara, Japan.

Objective: Inflammation is an important cause of tumorigenesis in various types of malignancy. Mediators derived from inflammatory cells are associated with cancer proliferation, angiogenesis, and DNA damage. In the present study, we immunohistochemically examined the infiltration patterns of inflammatory cells in benign glands including glandular hyperplasia, and in prostatic intraepithelial neoplasia and adenocarcinoma. Read More

Cancer Prev Res (Phila) 2013 Mar 28;6(3):232-41. Epub 2012 Dec 28.

College of Pharmacy, 336 Parks Hall, The Ohio State University, 500 West 12th Avenue, Columbus, OH 43210, USA.

Cells undergoing malignant transformation often exhibit a shift in cellular metabolism from oxidative phosphorylation to glycolysis. This glycolytic shift, called the Warburg effect, provides a mechanistic basis for targeting glycolysis to suppress carcinogenesis through the use of dietary caloric restriction and energy restriction-mimetic agents (ERMA). We recently reported the development of a novel class of ERMAs that exhibits high potency in eliciting starvation-associated cellular responses and epigenetic changes in cancer cells though glucose uptake inhibition. Read More

Cancer Lett 2013 Jun 29;334(1):142-51. Epub 2012 Nov 29.

Department of Dermatology, University of Wisconsin, Madison, WI, USA. Electronic address:

There is a need for developing improved therapeutic options for the management of prostate cancer, able to inhibit proliferation of precancerous and malignant lesions and/or to improve the effectiveness of conventional chemopreventive and chemotherapeutic agents. In this perspective, application of nanotechnology based strategies for the delivery of natural compounds for effective management of the disease is being actively researched. Here, after highlighting the most promising natural compounds for chemoprevention and chemotherapy of prostate cancer, the state of the art nanotherapeutics and the recent proof-of-concept of "nanochemoprevention", as well as the clinical development of promising targeted nanoprototypes for use in the prostate cancer treatment are being discussed. Read More

Nanomedicine 2012 Sep 26;8 Suppl 1:S31-6. Epub 2012 May 26.

Porto Conte Ricerche, Località Tramariglio, 07041, Alghero, Sassari, Italy.

The application of nanotechnology in medicine is offering many exciting possibilities in healthcare. Engineered nanoparticles have the potential to revolutionize the diagnosis and the therapy of several diseases, particularly by targeted delivery of anticancer drugs and imaging contrast agents. Prostate cancer, the second most common cancer in men, represents one of the major epidemiological problems, especially for patients in the advanced age. Read More

Dis Model Mech 2012 Nov 12;5(6):914-20. Epub 2012 Apr 12.

Department of Pharmaceutical and Biomedical Sciences, California Northstate University College of Pharmacy, Rancho Cordova, CA, USA.

Tp53 mutations are common in human prostate cancer (CaP), occurring with a frequency of ∼30% and ∼70% in localized and metastatic disease, respectively. In vitro studies have determined several common mutations of Tp53 that have specific gain-of-function properties in addition to loss of function, including the ability to promote castration-resistant (CR) growth of CaP cells in some contexts. To date, a lack of suitable mouse models has prohibited investigation of the role played by Tp53 mutations in mediating CaP progression in vivo. Read More

Med Arh 2012 ;66(1):41-4

Department of Urology, Clinical Centre University of Sarajevo, Sarajevo, Bosnia and Herzegovina.

Aim: Establish the main differences in the prostate volume, prostate specific antigen density (PSAD), number of biopsy samples in patients with primarily or rebiopsy detected prostate cancer.

Materials And Methods: In the 2007-2009 period, at the KCUS Urology Clinic, there were 379 TRUS guided prostate biopsies in 323 patients with known prostate volume. The total of 56 patients (17. Read More

Maturitas 2012 Sep 17;73(1):27-32. Epub 2012 Feb 17.

Porto Conte Ricerche, Località Tramariglio, Alghero, Sassari, Italy.

The application of nanotechnology in medicine is offering many exciting possibilities in healthcare. Engineered nanoparticles have the potential to revolutionize the diagnosis and the therapy of several diseases, particularly by targeted delivery of anticancer drugs and imaging contrast agents. Prostate cancer, the second most common cancer in men, represents one of the major epidemiological problems, especially for patients in the advanced age. Read More

Vopr Onkol 2011 ;57(4):486-92

Influence of selenium on induced carcinogenesis of the prostate and other organs was studied in male Wistar rats. Carcinogenesis was induced (68) by using our modification of a combined double-stage model including surgical castration, single administration of N-methyl-N-nitrosourea (MNU) and long-term promotion by a mix of testosterone ethers (MTE). Seven days after MNU injection the rats were randomized to form 2 groups. Read More

Endocrinology 2012 Jan 22;153(1):42-55. Epub 2011 Nov 22.

Department of Environmental Health, College of Medicine, University of Cincinnati, Cincinnati, Ohio 45267, USA.

Evidence supporting an early origin of prostate cancer is growing. We demonstrated previously that brief exposure of neonatal rats to estradiol or bisphenol A elevated their risk of developing precancerous lesions in the prostate upon androgen-supported treatment with estradiol as adults. Epigenetic reprogramming may be a mechanism underlying this inductive event in early life, because we observed overexpression of phosphodiesterase 4D variant 4 (Pde4d4) through induction of hypomethylation of its promoter. Read More

Biochem Res Int 2012 19;2012:398697. Epub 2011 Oct 19.

Division of Cancer Development System, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.

Epidemiological studies have shown that serum triglyceride (TG) levels are linked with risk of development of cancer, including colorectal and pancreatic cancers, and their precancerous lesions. Thus, it is assumed that serum TG plays an important role in carcinogenesis, and the key enzyme lipoprotein lipase (LPL), which catalyzes the hydrolysis of plasma TG, may therefore be involved. Dysregulation of LPL has been reported to contribute to many human diseases, such as atherosclerosis, chylomicronaemia, obesity, and type 2 diabetes. Read More

Prostate 2012 Jun 24;72(9):1013-22. Epub 2011 Oct 24.

Women's Health Department, MSD, Oss, The Netherlands.

Background: Prostate cancer is a common malignancy in men and although hormone ablation therapy is effective, men develop hormone resistance. There is need for therapies applicable earlier, such as treatment of prostatic intraepithelial neoplasia (PIN). Estrogens besides androgens play a role in prostate cancer pathogenesis via two receptors ERα and ERβ and both receptors are thought to play different, opposing, roles with ERα having proliferative properties and ERβ having anti-proliferative properties. Read More

BJU Int 2011 Nov 26;108(9):1394-401. Epub 2011 Aug 26.

Institute of Pathological Anatomy, School of Medicine, Polytechnic University of the Marche Region (Ancona), United Hospitals, Ancona, Italy.

The aim of the present paper was to review the morphological spectrum of prostatic intraepithelial neoplasia (PIN), its relationship to carcinoma of the prostate (PCa) and its clinical significance. We reviewed the literature on premalignant lesions of the prostate, with an emphasis on high grade prostatic intraepithelial neoplasia (HGPIN). HGPIN is the most likely precursor of PCa, according to almost all available evidence. Read More

Med Arh 2011 ;65(2):109-12

Department of Urology, KCUS, Bolnicka 24, Sarajevo, Bosnia and Herzegovina.

Objective: Establish the prostate cancer (PCa) detection rate and the premalignant lesion incidence, as well as their importance in cancer detection at the first rebiopsy.

Materials And Methods: In the period 2006-2008, at the CCUS Urology Clinic, there were 585 prostate biopsies performed in 515 patients. 12% of the patients underwent the first biopsy due to premalignant lesion findings. Read More

Am J Surg Pathol 2011 Jun;35(6):816-26

Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.

PAX8 is a paired-box gene important in embryogenesis of the thyroid, Müllerian, and renal/upper urinary tracts, and expression of PAX8 has been previously described in carcinomas from each of these sites. However, a large study including a wide variety of epithelial neoplasms from multiple organ sites other than the thyroid, kidney, or Müllerian system has not been performed. The goal of this study was to evaluate the utility of PAX8 immunostaining based on the evaluation of a wide range of epithelial tumors. Read More

Prostate 2011 Dec 7;71(16):1746-51. Epub 2011 Apr 7.

Department of Pathology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.

Background: Alpha-methylacyl-CoA racemase (AMACR) is highly expressed in prostatic adenocarcinoma. The precursor nature of atypical adenomatous hyperplasia (AAH) is uncertain.

Methods: One hundred twenty-one AAH foci from 101 patients who underwent transurethral prostatic resection or prostatectomy were immunohistochemically analyzed for AMACR, high molecular weight cytokeratin 34βE12, and p63 expression by a triple antibody (PIN4) cocktail stain. Read More

PLoS One 2011 Mar 4;6(3):e17449. Epub 2011 Mar 4.

Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.

MYC and phosphoinositide 3-kinase (PI3K)-pathway deregulation are common in human prostate cancer. Through examination of 194 human prostate tumors, we observed statistically significant co-occurrence of MYC amplification and PI3K-pathway alteration, raising the possibility that these two lesions cooperate in prostate cancer progression. To investigate this, we generated bigenic mice in which both activated human AKT1 and human MYC are expressed in the prostate (MPAKT/Hi-MYC model). Read More

Rev Med Chir Soc Med Nat Iasi 2010 Jul-Sep;114(3):818-22

Doctorand al Universităţii de Medicină şi Farmacie Gr.T. Popa Iaşi.

Unlabelled: The morphologic information from usual hematoxiline-eosine staining are sometimes insufficient in certifying or excluding the adenocarcinoma of the prostate, cases who must be study by immunohistochemistry.

Aim: The investigation of staining for CK5/6 and P63 in cases diagnosed with prostate adenocarcinoma associated with high grade prostatic intraepithelial neoplasia.

Material And Methods: The study was realized on 56 cases analyzed in Pathology Laboratory of Focşani Emergency Hospital. Read More

Cell Cycle 2011 Jan 15;10(2):268-77. Epub 2011 Jan 15.

Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX, USA.

It is well established that protein kinase C (PKC) isozymes play distinctive roles in mitogenic and survival signaling as well as in cancer progression. PKCε, the product of the PRKCE gene, is up-regulated in various types of cancers including prostate, lung and breast cancer. To address a potential role for PKCs in prostate cancer progression we generated three mouse transgenic lines expressing PKCα, PKCδ, or PKCε in the prostate epithelium under the control of the rat probasin (PB) promoter. Read More

BMC Cancer 2010 Dec 13;10:680. Epub 2010 Dec 13.

Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, 10833 Le Conte Ave, Los Angeles, CA 90095, USA.

Background: The protein AGR2 is a putative member of the protein disulfide isomerase family and was first identified as a homolog of the Xenopus laevis gene XAG-2. AGR2 has been implicated in a number of human cancers. In particular, AGR2 has previously been found to be one of several genes that encode secreted proteins showing increased expression in prostate cancer cells compared to normal prostatic epithelium. Read More

Biochim Biophys Acta 2011 Feb 6;1809(2):119-27. Epub 2010 Sep 6.

Department of Biochemistry & Molecular Biology, Universityof Miami Miller School of Medicine, Miami, FL 33136, USA.

This study elucidates the role of E6-associated protein, E6-AP (a dual function steroid hormone receptor coactivator and ubiquitin-protein ligase) in the regulation of PI3K-Akt signaling pathway, prostate gland growth and proliferation. Here, we report the generation of transgenic mice and prostate cancer cell line, LNCaP cells that overexpress E6-AP protein. Using these models we show that the levels of total Akt and phosphorylated Akt (active Akt) are increased in E6-AP overexpressing prostate gland and LNCaP cells suggesting that E6-AP regulates the PI3K-Akt signaling pathway. Read More

Urol Oncol 2011 Nov-Dec;29(6):690-7. Epub 2010 May 7.

Division of Urology, Department of Surgery, Policlinico Tor Vergata, University of Tor Vergata, Rome, Italy.

Objectives: To evaluate the prevalence and short-term follow-up of focal proliferative atrophy lesions, either with or without the presence of inflammation (PIA/PA), and its correlation with the PSA levels, focusing on the prostate biopsy cores that test negative for prostate adenocarcinoma (PCa).

Methods: Five hundred fifty consecutive patients who had undergone a transrectal ultrasound-guided transperineal prostate biopsy were evaluated retrospectively for the presence and follow-up of focal proliferative atrophy lesions. PIA/PA were defined according to De Marzo. Read More

Endocr Relat Cancer 2010 Jun 18;17(2):505-12. Epub 2010 May 18.

Department of Urology of Minimally Invasive Surgery Center, the First Affiliated Hospital of Guangzhou Medical College, No. 1-3, Kangda Road, Guangzhou 510230, Guangdong Province, People's Republic of China.

Early prostate cancer antigen (EPCA) has been recently suggested as a novel biomarker in malignant and premalignant lesions of the prostate. This study was to examine serum expression of EPCA and to further clarify the relationship between initial serum EPCA levels and the presence of subsequent cancer in the individuals with isolated high-grade prostatic intraepithelial neoplasia (HGPIN). An indirect ELISA was used for initial serum EPCA measurement in 112 men with isolated HGPIN, who were enrolled and completed a follow-up of >or=5 years. Read More

Am J Pathol 2009 Sep 21;175(3):1187-99. Epub 2009 Aug 21.

Centre for Urological Research, Monash Institute of Medical Research, Monash University, 27-31 Wright Street, Clayton, Victoria 3168, Australia.

Prostatitis causes substantial morbidity to men, through associated urinary symptoms, sexual dysfunction, and pelvic pain; however, 90% to 95% of cases have an unknown etiology. Inflammation is associated with the development of carcinoma, and, therefore, it is imperative to identify and study the causes of prostatitis to improve our understanding of this disease and its role in prostate cancer. As estrogens cause prostatic inflammation, here we characterize the murine prostatic phenotype induced by elevated endogenous estrogens due to aromatase overexpression (AROM+). Read More

Prostate 2009 Sep;69(13):1378-86

Department of Urology, Lundberg Laboratory for Cancer Research, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.

Background: Inflammation has been implicated as a potential etiological agent in human prostate cancer (PCa). Proliferative inflammatory atrophy (PIA) in prostate consists of areas of glandular atrophy associated with chronic inflammation and epithelial cell proliferation. It has been suggested that PIA is a candidate precursor of prostate malignancy. Read More

PLoS One 2008 15;3(12):e3940. Epub 2008 Dec 15.

Department of Biochemistry and Molecular Biology, and The McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, Alberta, Canada.

Loss of the PTEN tumor suppressor is a common occurrence in human prostate cancer, particularly in advanced disease. In keeping with its role as a pivotal upstream regulator of the phosphatidylinositol 3-kinase signaling pathway, experimentally-induced deletion of Pten in the murine prostate invariably results in neoplasia. However, and unlike humans where prostate tumorigenesis likely evolves over decades, disease progression in the constitutively Pten deficient mouse prostate is relatively rapid, culminating in invasive cancer within several weeks post-puberty. Read More

Virchows Arch 2009 Jan 2;454(1):1-16. Epub 2008 Dec 2.

Departments of Pathology, Urology and Oncology, The Johns Hopkins Hospital, 401 N. Broadway St., Rm 2242, Baltimore, MD, 21231, USA.

High-grade prostatic intraepithelial neoplasia (PIN) is the one well-documented precursor to adenocarcinoma of the prostate. This review article defines both low- and high-grade PIN. Unusual variants of high-grade PIN are illustrated. Read More

Best Pract Res Clin Endocrinol Metab 2008 Apr;22(2):285-91

Bostwick Laboratories Inc, Glen Allen, VA 23060, USA.

Androgen deprivation therapy has become well-established in the treatment of prostate cancer. Luteinizing-hormone-releasing hormone (LHRH) agonists, anti-androgens, orchiectomy, and combination hormonal therapy are treatment options offered to select patients. The prospect of intervention prior to the development of adenocarcinoma is appealing, and high-grade prostate intra-epithelial neoplasia (PIN), the only known precursor, is the best possible target. Read More

Andrologia 2008 Apr;40(2):134-7

Institute of Pathology, University of Giessen and Marburg, Giessen, Germany.

Proliferative inflammatory atrophy (PIA) belongs to the atrophic lesions that frequently occur in the prostate. The location of PIA in the periphery of the gland near to prostate carcinoma or even showing direct transition to malignant or pre-malignant epithelia suggested a connection between PIA and prostate cancer. Further findings in PIA, such as imbalance between proliferation and apoptosis and detection of molecular-biological abnormalities specific for oxidative stress or malignancy, supported this hypothesis. Read More

Prostate 2008 May;68(7):728-39

Institute of Biomedicine, Department of Anatomy, University of Turku, Turku, Finland.

Background: Chronic inflammation may contribute to the development of prostate cancer. The goal of this study was to determine the possible association of prostatic inflammation, prostatic intraepithelial neoplasia (PIN)-like lesion, and prostate cancer, and to assess the androgen and estrogen dependency of the early steps of carcinogenesis.

Methods: Noble rats were treated with testosterone and estradiol implants for 13, 18, or 26 weeks. Read More

Basic Clin Pharmacol Toxicol 2008 Feb;102(2):134-8

Department of Urology, University of Illinois at Chicago, Chicago, IL, USA.

An important and controversial health concern is whether low-dose exposures to hormonally active environmental oestrogens such as bisphenol A can promote human diseases including prostate cancer. Our studies in rats have shown that pharmacological doses of oestradiol administered during the critical window of prostate development result in marked prostate pathology in adulthood that progress to neoplastic lesions with ageing. Our recent studies have also demonstrated that transient developmental exposure of rats to low, environmentally relevant doses of bisphenol A or oestradiol increases prostate gland susceptibility to adult-onset precancerous lesions and hormonal carcinogenesis. Read More