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American Journal of Clinical and Experimental Urology

Peter A Raven, Ninadh M D'Costa, Igor Moskalev, Zheng Tan, Sebastian Frees, Claudia Chavez-Munoz, Alan I So
We have developed a murine intravesical orthotopic human bladder cancer (mio-hBC) model for the establishment of superficial urothelial cell carcinomas. In this model we catheterize female atyhmic nude mice and pre-treat the bladder with poly-L-lysine for 15 minutes, followed by intravesical instillation of luciferase-transfected human UM-UC-3 cells. Cancer cells are quantified by bioluminescent imaging which has been validated by small animal ultrasound. Poly-L-lysine pre-treatment increased engraftment rate (84...
2018: American Journal of Clinical and Experimental Urology
Mingming Zhong, Laura E Pascal, Erdong Cheng, Khalid Z Masoodi, Wei Chen, Anthony Green, Brian W Cross, Erica Parrinello, Lora H Rigatti, Zhou Wang
Elongation factor for RNA polymerase II 2 (ELL2) and ELL-associated factor 2 (EAF2) are two functionally related androgen responsive gene-encoded proteins with prostate tumor suppressor characteristics. EAF2 and ELL2 have both been shown to be down-regulated in advanced prostate cancer, and mice with either Eaf2 or Ell2 deficiency developed murine prostatic intraepithelial neoplasia (mPIN), increased cellular proliferation and increased vascularity. Functional studies have revealed that EAF2 and ELL2 can bind to each other and have similar roles in regulating cell proliferation, angiogenesis and prostate homeostasis...
2018: American Journal of Clinical and Experimental Urology
Ali Hashemi Gheinani, Ivonne Köck, Evalynn Vasquez, Ulrich Baumgartner, Alexander Bigger-Allen, Bryan S Sack, Fiona C Burkhard, Rosalyn M Adam, Katia Monastyrskaya
Bladder outlet obstruction (BOO) leads to lower urinary tract symptoms (LUTS) and urodynamic changes of the bladder function. Previously we identified microRNA (miRNA) and mRNA expression profiles associated with different states of BOO-induced LUTD in human patients. Bladder wall remodeling resulting from obstruction is widely studied in animal models of experimentally-induced partial BOO (pBOO). Here we determined the expression profiles of miRNAs and selected mRNAs in pBOO mice and compared the observed changes to human patients...
2018: American Journal of Clinical and Experimental Urology
Diya B Joseph, Douglas W Strand, Chad M Vezina
Epigenetic mechanisms including DNA methylation are critical regulators of organismal development and tissue homeostasis. DNA methylation is the transfer of methyl groups to cytosines, which adds an additional layer of complexity to the genome. DNA methylation marks are recognized by the cellular machinery to regulate transcription. Disruption of DNA methylation with aging or exposure to environmental toxins can change susceptibility to disease or trigger processes that lead to disease. In this review, we provide an overview of the DNA methylation machinery...
2018: American Journal of Clinical and Experimental Urology
Nicholas M Tassone, Belinda Li, Megan Y Devine, Paulette M Hausner, Mehul S Patel, Andrew D Gould, Kirsten S Kochan, Robert W Dettman, Edward M Gong
The partial bladder outlet obstruction animal model (pBOO) is commonly used as a model for obstructive uropathy. Unfortunately, pBOO demonstrates variable degrees of obstruction requiring bladder weight (BW) or urodynamic studies to determine true obstruction. Our objective is to identify extent of obstruction by correlating early post-operative Void Stains on Paper (VSOP) assays with ultimate BW in mice. pBOO was performed on 32 mice 1- and 4-week VSOPs were quantified for mean voided volume (mVV). At 4 weeks, bladders were harvested and weighed...
2018: American Journal of Clinical and Experimental Urology
Hongying Huang, Sergei R Guma, Jonathan Melamed, Ming Zhou, Peng Lee, Fang-Ming Deng
BACKGROUND: Prostate specific antigen (PSA), prostate specific membrane antigen (PSMA), and NKX3.1 are sensitive and prostate-specific markers frequently used for the diagnosis of metastatic prostate cancer (mPCa). International Society of Urological Pathology recommends use of PSA as the initial immunohistochemical (IHC) marker to identify PCa. If the tumor is equivocal/weak/negative for PSA, then P501S and NKX3.1 stains are suggested. However, no specific studies have attempted to compare the staining sensitivity of these markers post specimen decalcification of bone specimens...
2018: American Journal of Clinical and Experimental Urology
Zachary M Connelly, Shu Yang, Fenghua Chen, Yunshin Yeh, Nazih Khater, Renjie Jin, Robert Matusik, Xiuping Yu
Prostate cancer (PCa) is the leading cancer among men. Androgen Deprivation Therapy (ADT) is a common treatment for advanced PCa. However, ADT eventually fails and PCa relapses, developing into castration-resistant prostate cancer (CRPCa). Although alternative pathways such as cancer stem-cell pathway and neuroendocrine differentiation bypass androgen receptor (AR) signaling, AR remains the central player in mediating CRPCa. In this study, we identified a mechanism that retains AR signaling after androgen deprivation...
2018: American Journal of Clinical and Experimental Urology
Hironobu Yamashita, Lauren Shuman, Joshua I Warrick, Jay D Raman, David J Degraff
Opioid receptors are G protein-coupled receptors that bind opioid ligands including endorphins and enkephalins. The existence of a number of opioid receptors, including the mu-opioid receptor (OPRM1), delta-opioid receptor (OPRD1), kappa-opioid receptor (OPRK1) and zeta-opioid receptor (OGFR) have been reported. However, the potential expression and role of these receptors on human prostate carcinogenesis is unknown. In the present study, we examined opioid receptor expression in human prostate cancer cell lines and in prostate cancer tissue...
2018: American Journal of Clinical and Experimental Urology
Ikenna C Madueke, Wen-Yang Hu, Liwei Huang, Gail S Prins
Wnt proteins are highly conserved secreted morphogens that function in organ development across species. This study investigates the role(s) of Wnt2 during prostate gland development. Wnt2 mRNA ontogeny in the rat ventral prostate rapidly declines in expression from peak value at post-natal day (pnd) 1 to nadir levels sustained through adulthood. Wnt2 mRNA is expressed in prostate mesenchymal cells and Wnt2 protein localizes to both mesenchymal and epithelial cells. Sustained expression of Wnt2 by adenoviral expression during rat postnatal prostate gland development resulted in significant reduction in gland size confirming its necessary decline to permit normal development...
2018: American Journal of Clinical and Experimental Urology
Nicola Zampieri, Francesco Saverio Camoglio
Preserving the fertility potential of adolescent patients with varicocele is still the main outcome of pediatric and adolescent urologysts; the aim of this study is to assess the fertility potential of patients treated for varicocele with testicular hypotrophy in absence of post-operative complications, with complete ipsilateral testicular catch-up growth and normal hormonal values. METHODS: The Authors collected data from adolescents with varicocele aged between 10 and 16 years treated at their Institution between September 2010 and September 2015...
2018: American Journal of Clinical and Experimental Urology
Swathi Ramakrishnan, Wendy Huss, Barbara Foster, Joyce Ohm, Jianmin Wang, Gissou Azabdaftari, Kevin H Eng, Anna Woloszynska-Read
Cancer cells set in motion transcriptomic programs allowing for adaptation and growth in immunocompromised mice to form xenografts, a frequently used tool in cancer research. 2D cultures may not be representative of tumors growing in a complex host microenvironment. This can result in different responses to the same agent tested in vitro and in vivo which impedes the process of developing novel therapeutics. Understanding the transition cells undergo from 2D cell culture to a 3D host microenvironment will help in developing and choosing appropriate models for pre-clinical studies...
2018: American Journal of Clinical and Experimental Urology
Nicola Zampieri, Virginia Murri, Francesco Saverio Camoglio
OBJECTIVE: To report our experience with post-operative use of human chorionic gonadotrophin to achieve higher testicular volume and function, respect to untreated patients. MATERIALS AND METHODS: A prospective study was done using subjects who underwent orchidopexy between Sptember 2010 and September 2016 for unilateral intrabdominal undescended testes. All patients were treated by the same surgeon with laparoscopic one-stage Fowler-Stephens technique. After surgery (2 weeks) those patient parents who accepted to use hormonal therapy, had to follow a 6 weeks scheme...
2018: American Journal of Clinical and Experimental Urology
Tyler Etheridge, Jinning Liou, Tracy M Downs, E Jason Abel, Kyle A Richards, David F Jarrard
Recent work suggests the selective Cox-2 inhibitor celecoxib delays progression to androgen independence in hormone sensitive prostate cancer (HSPC) through inhibition of the androgen receptor (AR) and ErbB signaling. However, human studies examining its effect on delaying disease progression while on hormone therapy are limited. This study explores the effect of celecoxib use on PC survival in VA patients undergoing androgen deprivation therapy (ADT) for advanced PC. We retrospectively examined the association between celecoxib use (defined as duration of medication use ≥180 days) in men with PC being treated with ADT in national VA databases...
2018: American Journal of Clinical and Experimental Urology
David Cunningham, Qiuyang Zhang, Sen Liu, Keshab R Parajuli, Qiang Nie, Lin Ma, Allen Zhang, Zhenbang Chen, Zongbing You
Metastasis of prostate cancer causes substantial morbidity and mortality. The role of chronic inflammatory factors in promoting the development of prostate cancer metastasis remains unexamined due to a lack of immunocompetent animal models. Here we report an orthotopic mouse allograft model of prostate cancer that was used to assess interleukin-17's role in prostate cancer metastasis. A luciferase gene was stably introduced into a mouse prostate cancer cell line MPC3, named as MPC3-luc. MPC3-luc cells were mixed with Matrigel™ and inoculated into C57BL/6 mouse prostates, with recombinant mouse interleukin-17 (IL-17) (treatment group) or without IL-17 (control group)...
2018: American Journal of Clinical and Experimental Urology
William G Nelson, Michael C Haffner, Srinivasan Yegnasubramanian
Donald S. Coffey, a pioneer in the study of the structural basis of mammalian genome organization, was fascinated by DNA topoisomerases, chemo-mechanical enzymes that could catalyze changes in DNA structure. Work initiated in his laboratory and carried on with his influence and inspiration has led to the elucidation of specific roles for each of the two type 2 topoisomerases in DNA replication, RNA transcription, and androgen action in prostate cells. TOP2A principally acts in DNA synthesis elongation to prevent tangling of daughter DNA molecules during genome replication and mitotic segregation; TOP2B is required for androgen-stimulation of target gene transcription...
2018: American Journal of Clinical and Experimental Urology
James L Mohler
This mini-review describes the evolution of the concept of intracrine androgen metabolism by prostate cancer during androgen deprivation therapy. Persistence of androgen receptor protein in the face of castrate circulating levels of testosterone could not be explained fully by hypersensitization or mutation of the androgen receptor. The hypothesis that castration-recurrent prostate cancer produced its own testosterone was proven using radioimmunoassay and mass spectrometry methods adopted for use in prostate tissue...
2018: American Journal of Clinical and Experimental Urology
Alan K Meeker
This mini-review article discusses past and present prostate-focused research on telomere and telomerase biology conducted at Johns Hopkins, through the eyes of a Donald S Coffey trainee. Included are past discoveries of abnormalities in telomere biology in the context of prostate cancer and its pre-malignant precursor prostatic intraepithelial neoplasia (PIN); the finding that telomerase activity is androgen-regulated in the prostate, and the potential role of telomerase in prostate epithelial stem cells. Also reviewed are more recent results showing that in situ telomere length measurements in patient tissue specimens may have utility in risk assessment and as a prognostic biomarker...
2018: American Journal of Clinical and Experimental Urology
William Steven Ward
In early years, Dr. Donald S. Coffey fostered the development of a new model for the organization of DNA in the sperm nucleus that had many unexpected similarities to that of somatic cells. This was surprising because it was well known that mammalian sperm DNA is more compact than the DNA in mitotic chromosomes, and the fact that some of the major structural components of somatic cell DNA organization were retained in the sperm cell was not predicted. The highly compact sperm DNA is organized into loop domains that are attached at their bases to a proteinaceous nuclear matrix, at specific matrix attachment regions (MARs)...
2018: American Journal of Clinical and Experimental Urology
Shawn E Lupold
This mini-review article is part of a special issue dedicated to Donald S. Coffey, a pioneer translational research scientist, exemplary mentor, and leader in urologic and urologic oncology research. This article first briefly reflects on life and scientific lessons from Don Coffey. It then reviews the development of two prostate cancer targeting RNA aptamers, xPSM-A9 and xPSM-A10, through in vitro selection for aptamers that bind to the extracellular domain of the Prostate Specific Membrane Antigen (PSMA)...
2018: American Journal of Clinical and Experimental Urology
Partha P Banerjee, Subhadra Banerjee, Terry R Brown, Barry R Zirkin
Benign prostatic hyperplasia (BPH) is an enlargement of the prostate gland that is frequently found in aging men. Androgens are essential for the development and differentiated function of the prostate, as well as for proliferation and survival of prostatic cells. In man, dog and rodent, there are age-related decreases in serum testosterone. Despite the lower serum testosterone levels, benign prostatic hyperplasia increases with age in men and dogs, while age-dependent prostatic hyperplasia develops in the dorsal and lateral lobes of the rat prostate...
2018: American Journal of Clinical and Experimental Urology
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