Search Our Scientific Publications & Authors

Cancer Prev Res (Phila) 2021 06 1;14(6):635-648. Epub 2021 Mar 1.

School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Texas.

We reported efficacy of Nakai (AGN) root ethanol extract and equimolar decursin (D)/decursinol angelate (DA) through daily gavage starting at 8 weeks of age (WOA) to male transgenic adenocarcinoma of mouse prostate (TRAMP) mice such that these modalities suppressed precancerous epithelial lesions in their dorsolateral prostate (DLP) to similar extent, but AGN extract was better than the D/DA mixture at promoting the survival of mice bearing prostate neuroendocrine carcinomas to 28 WOA. Here, we compared by microarray hybridization the mRNA levels in pooled DLP tissues and individual neuroendocrine carcinomas to characterize potential molecular targets of AGN extract and D/DA. Clustering and principal component analyses supported distinct gene expression profiles of TRAMP DLP versus neuroendocrine carcinomas. Read More

Life Sci 2020 Feb 9;242:117149. Epub 2019 Dec 9.

Department of Morphology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. Electronic address:

Aims: The purpose of this study was to describe a suitable experimental model for studying aging-related prostate disorders including cancer.

Materials And Methods: 12-month old Wistar rats were kept in control conditions (n = 12) or treated (n = 16) for 6 months with Silastic implants filled with testosterone (T) and estradiol (E). After the experiment period (at 18 months of age), animals were euthanized and the prostate and other organs were harvested, dissected, weighed, and processed for morphological, ultrastructural and molecular analyses. Read More

Exp Oncol 2019 06;41(2):130-137

Centro de Investigaciones Cerebrales, Universidad Veracruzana, Xalapa 91193, Veracruz, México.

Stress during puberty and obesity can represent conditions that facilitate the long-term development of diseases, especially for stress-related disorders that depend on neuroendocrine and immune responses. The prostate is 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) or obesity on the development of precancerous lesions in rats. Read More

Histopathology 2019 Jun 21;74(7):1036-1044. Epub 2019 Apr 21.

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

Prostate 2019 04 25;79(5):515-535. Epub 2018 Dec 25.

Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.

Background: Chronic inflammation has been implicated in cancer etiology and angiogenesis is stimulated in this disease. In prostate, the crosstalk between malignant epithelial cells and their microenvironment is an essential step of tumorigenesis during which glandular stroma undergo changes designated as reactive stroma. Thus, the aim herewith was to evaluate the effects of associating anti-inflammatory and antiangiogenic therapies on cancer progression, correlating them with steroid hormone receptor (AR and ERα), reactive stroma (vimentin, αSMA, and TGF-β), and cell proliferation (PCNA) markers expression in the Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) model. Read More

Invest Radiol 2019 03;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