renal-capsule-xenografting-subcutaneous-pellet-implantation-for

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

New therapies for two common prostate diseases,  prostate cancer (PrCa) and benign prostatic hyperplasia (BPH), depend  critically on experiments ...

ultrasonography-adult-male-urinary-tract-for-urinary-functional

Ultrasonography of the Adult Male Urinary Tract for Urinary Functional Testing

The incidence of clinical benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS) is increasing due to the aging population, resulting ...

University of Wisconsin-Madison

University of Rochester School of Medicine & Dentistry

University of Washington

Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms (LUTS) are common clinical problems in urology. While the precise molecular etiology remains unclear, sex steroids have been implicated in the development and maintenance of BPH. Sufficient data exists linking androgens and androgen receptor pathways to BPH and use of androgen reducing compounds, such as 5Î±-reductase inhibitors which block the conversion of testosterone into dihydrotestosterone, are a component of the standard of care for men with LUTS attributed to an enlarged prostate. However, BPH is a multifactorial disease and not all men respond well to currently available treatments, suggesting factors other than androgens are involved. Testosterone, the primary circulating androgen in men, can also be metabolized via CYP19/aromatase into the potent estrogen, estradiol-17Î². The prostate is an estrogen target tissue and estrogens directly and indirectly affect growth and differentiation of prostate. The precise role of endogenous and exogenous estrogens in directly affecting prostate growth and differentiation in the context of BPH is an understudied area. Estrogens and selective estrogen receptor modulators (SERMs) have been shown to promote or inhibit prostate proliferation signifying potential roles in BPH. Recent research has demonstrated that estrogen receptor signaling pathways may be important in the development and maintenance of BPH and LUTS; however, new models are needed to genetically dissect estrogen regulated molecular mechanisms involved in BPH. More work is needed to identify estrogens and associated signaling pathways in BPH in order to target BPH with dietary and therapeutic SERMs.

Androgens and estrogens in benign prostatic hyperplasia: past, present and future.

L&#39;hyperplasie b&eacute;nigne de la prostate (HBP) et sympt&ocirc;mes associ&eacute;s &agrave; des voies urinaires inf&eacute;rieurs (LUTS) sont des probl&egrave;mes communs de cliniques en urologie. Alors qu&#39;on ne sait pas l&#39;&eacute;tiologie mol&eacute;culaire pr&eacute;cis, les st&eacute;ro&iuml;des sexuels ont &eacute;t&eacute; impliqu&eacute;s dans le d&eacute;veloppement et la maintenance de l&#39;HBP. Donn&eacute;es suffisantes existent reliant androg&egrave;nes et voies du r&eacute;cepteur aux androg&egrave;nes BPH et l&#39;utilisation des androg&egrave;nes, r&eacute;duction des compos&eacute;s, tels que les inhibiteurs de la 5&alpha;-r&eacute;ductase qui bloquent la conversion de la testost&eacute;rone en dihydrotestost&eacute;rone, sont un composant de la norme de soins pour hommes avec LUTS attribu&eacute;e &agrave; une hypertrophie de la prostate. Toutefois, l&#39;HBP est une maladie multifactorielle, et pas tous les hommes r&eacute;pondent bien aux traitements actuellement disponibles, ce qui sugg&egrave;re des facteurs autres que les androg&egrave;nes jouent un r&ocirc;le. Testost&eacute;rone, le principal androg&egrave;ne circulant chez les hommes, peut aussi &ecirc;tre m&eacute;tabolis&eacute;e par CYP19/aromatase dans le &oelig;strog&egrave;ne puissant, estradiol-17&beta;. La prostate est un tissu de cible d&#39;oestrog&egrave;ne et oestrog&egrave;nes touchent directement et indirectement la croissance et la diff&eacute;renciation de la prostate. Le r&ocirc;le pr&eacute;cis des estrog&egrave;nes endog&egrave;nes et exog&egrave;nes en affectant directement la croissance de la prostate et de la diff&eacute;renciation dans le contexte de l&#39;HBP est une zone peu &eacute;tudi&eacute;e. Oestrog&egrave;nes et modulateurs de r&eacute;cepteurs de &oelig;strog&egrave;nes (SERMs) montrent &agrave; promouvoir ou &agrave; inhiber la prolif&eacute;ration de la prostate qui signifie les r&ocirc;les possibles dans l&#39;HBP. Recherches r&eacute;centes ont d&eacute;montr&eacute; que r&eacute;cepteur des oestrog&egrave;nes signalisation de voies peuvent &ecirc;tre importants dans le d&eacute;veloppement et la maintenance de BPH et LUTS ; Cependant, les nouveaux mod&egrave;les sont n&eacute;cessaires pour diss&eacute;quer g&eacute;n&eacute;tiquement oestrog&egrave;ne r&eacute;glement&eacute; les m&eacute;canismes mol&eacute;culaires impliqu&eacute;s dans l&#39;HBP. Plus de travail est n&eacute;cessaire pour identifier des oestrog&egrave;nes et associ&eacute;s des voies de signalisation en HBP afin de cibler les BPH avec SERMs di&eacute;t&eacute;tiques et th&eacute;rapeutiques.

Les androg&egrave;nes et les oestrog&egrave;nes en hyperplasie b&eacute;nigne de la prostate : pass&eacute;, pr&eacute;sent et futur.

Iperplasia prostatica benigna (BPH) e sintomi associati inferiori del tratto urinario (LUTS) sono comuni problemi clinici in urologia. Mentre la precisa eziologia molecolare rimane poco chiaro, steroidi del sesso sono stati implicati nello sviluppo e nella manutenzione di BPH. Esistono sufficienti dati che collega gli androgeni e percorsi del recettore androgeno di BPH e uso di androgeni, riduzione di composti, come gli inibitori della 5 &alpha;-reduttasi che bloccano la conversione del testosterone in diidrotestosterone, sono una componente dello standard di cura per gli uomini con LUTS attribuita ad un ingrossamento della prostata. Tuttavia, BPH &egrave; una malattia multifattoriale e non tutti gli uomini rispondono bene ai trattamenti attualmente disponibili, suggerendo che fattori di androgeni sono implicati. Testosterone, il principale androgeno circolante negli uomini, pu&ograve; essere metabolizzato via CYP19/aromatasi in potente estrogeno, estradiolo-17 &beta;. La prostata &egrave; un tessuto bersaglio degli estrogeni ed estrogeni direttamente e indirettamente influenzano la crescita e la differenziazione della prostata. Il ruolo preciso di estrogeni endogeni ed esogeni che colpiscono direttamente la crescita della prostata e differenziazione nel contesto della BPH &egrave; un&#39;area understudied. Estrogeni e selective estrogen receptor modulatori (SERMs) hanno dimostrati di promuovere o inibire la proliferazione della prostata significare ruoli potenziali nella BPH. Recenti ricerche hanno dimostrato che estrogeno recettore signaling pathways pu&ograve; essere importante nello sviluppo e nella manutenzione di BPH e LUT; Tuttavia, nuovi modelli sono necessari per sezionare geneticamente estrogeni regolato meccanismi molecolari coinvolti nella BPH. Pi&ugrave; lavoro &egrave; necessario per identificare gli estrogeni e associati signaling pathways in BPH per BPH con SERMs dietetico e terapeutico di destinazione.

Androgeni ed estrogeni nella iperplasia prostatica benigna: passato, presente e futuro.

Angiomyolipoma is a rare benign tumor most commonly found in the kidney and, infrequently, extrarenally. We report a case of pelvic angiomyolipoma in a male patient without stigmata of tuberous sclerosis. The patient presented with right retroperitoneal bleeding and was found to have bilateral renal angiomyolipomas as well as a pelvic mass with similar appearance as the other lesions. He underwent urgent embolization of the large right angiomyolipoma and subsequent robot-assisted left laparoscopic partial nephrectomy with simultaneous resection of the pelvic mass, which was well-tolerated. Pathology confirmed what is, to our knowledge, the only reported case of pelvic angiomyolipoma.

Pelvic angiomyolipoma.

Angiomyolipome est une tumeur b&eacute;nigne rare, le plus souvent trouv&eacute;e dans les reins et, rarement, extrarenally. Nous rapportons le cas d&#39;un Angiomyolipome pelvien chez un patient m&acirc;le sans les stigmates de la scl&eacute;rose tub&eacute;reuse de Bourneville. Le patient a pr&eacute;sent&eacute; une h&eacute;morragie r&eacute;trop&eacute;riton&eacute;ale droite et s&#39;est av&eacute;r&eacute; pour avoir Angiomyolipome r&eacute;nal bilat&eacute;ral ainsi qu&#39;une masse pelvienne avec une apparence similaire comme les autres l&eacute;sions. Il a subi une embolisation urgente des gros angiomyolipomes droite et ult&eacute;rieure assist&eacute;e par robot gauche laparoscopique n&eacute;phrectomie partielle avec r&eacute;section simultan&eacute;e de la masse pelvienne, qui a &eacute;t&eacute; bien tol&eacute;r&eacute;e. Pathologie a confirm&eacute; ce qui est, &agrave; notre connaissance, le seul cas signal&eacute; d&#39;Angiomyolipome pelvienne.

Angiomyolipome pelvienne.

Angiomyolipoma &egrave; un tumore benigno raro che pi&ugrave; comunemente si trovano nel rene e, meno frequentemente, extrarenally. Riportiamo un caso di angiomyolipoma pelvica in un paziente maschio senza Stigmate di sclerosi tuberosa. Il paziente ha presentato con l&#39;emorragia retroperitoneale destra ed &egrave; stato trovato per avere angiomiolipomi renali bilaterali, nonch&eacute; una massa pelvica con aspetto simile come le altre lesioni. Egli sub&igrave; embolizzazione urgente della grande destra angiomyolipoma e successivo robot-assistita sinistra laparoscopica parziale nefrectomia con resezione simultanea della massa pelvica, che &egrave; stato ben tollerata. Patologia ha confermato ci&ograve; che &egrave;, a nostra conoscenza, l&#39;unico caso segnalato di angiomyolipoma pelvica.

Angiomyolipoma pelvica.

The majority of blunt renal trauma is a consequence of motor vehicle collisions and falls. Prior publications based on urban series have shown that significant renal injuries are almost always accompanied by gross hematuria alone or microscopic hematuria with concomitant hypotension. We present a series of blunt renal trauma sustained during recreational pursuits, and describe the mechanisms, injury patterns and management.

Renal trauma from recreational accidents manifests different injury patterns than urban renal trauma.

La majorit&eacute; de contusion r&eacute;nale est une cons&eacute;quence des collisions de v&eacute;hicules motoris&eacute;s et tombe. Les publications ant&eacute;rieures bas&eacute;es sur la s&eacute;rie urbaine ont montr&eacute; qu&#39;importantes l&eacute;sions r&eacute;nales sont presque toujours accompagn&eacute;es d&#39;h&eacute;maturie seul ou microscopiques de H&eacute;maturie franche avec hypotension concomitante. Nous pr&eacute;sentons une s&eacute;rie de contusion r&eacute;nale subie au cours d&#39;activit&eacute;s r&eacute;cr&eacute;atives et d&eacute;crire les m&eacute;canismes, de patrons de blessures et de gestion.

Traumatisme r&eacute;nal d&#39;accidents de loisirs manifeste injury diff&eacute;rents patterns qu&#39;urbain traumatisme r&eacute;nal.

La maggior parte del trauma contusivo renale &egrave; una conseguenza della collisione di veicoli a motore e cade. Pubblicazioni precedenti basate sulla serie urban hanno dimostrato che lesioni renali significative sono quasi sempre accompagnati da ematuria microscopica o solo di ematuria lordo con ipotensione concomitante. Noi presentiamo una serie di trauma contusivo renale subito durante gli inseguimenti di ricreazione e descrivere i meccanismi, modelli di infortunio e gestione.

Renali traumi da incidenti ricreativi si manifesta modelli differenti lesioni pi&ugrave; urbano trauma renale.

Benign prostatic hyperplasia (BPH) and bladder outlet obstruction (BOO) are common in older men and can contribute to lower urinary tract symptoms that significantly impact quality of life. Few existing models of BOO and BPH use physiological levels of hormones associated with disease progression in humans in a genetically manipulable organism. We present a model of BPH and BOO induced in mice with testosterone (T) and 17Î²-estradiol (E(2)). Male mice were surgically implanted with slow-releasing sc pellets containing 25 mg T and 2.5 mg E(2) (T+E(2)). After 2 and 4 months of hormone treatment, we evaluated voiding patterns and examined the gross morphology and histology of the bladder, urethra, and prostate. Mice treated with T+E(2) developed significantly larger bladders than untreated mice, consistent with BOO. Some mice treated with T+E(2) had complications in the form of bladder hypertrophy, diverticula, calculi, and eventual decompensation with hydronephrosis. Hormone treatment caused a significant decrease in the size of the urethral lumen, increased prostate mass, and increased number of prostatic ducts associated with the prostatic urethra, compared with untreated mice. Voiding dysfunction was observed in mice treated with T+E(2), who exhibited droplet voiding pattern with significantly decreased void mass, shorter void duration, and fewer sustained voids. The constellation of lower urinary tract abnormalities, including BOO, enlarged prostates, and voiding dysfunction seen in male mice treated with T+E(2) is consistent with BPH in men. This model is suitable for better understanding molecular mechanisms and for developing novel strategies to address BPH and BOO.

Testosterone and 17Î²-estradiol induce glandular prostatic growth, bladder outlet obstruction, and voiding dysfunction in male mice.

L&#39;hyperplasie b&eacute;nigne de la prostate (HBP) et obstruction de la vessie prise (BOO) sont fr&eacute;quents chez les hommes &acirc;g&eacute;s et peuvent contribuer &agrave; des sympt&ocirc;mes du bas appareil urinaire influant sensiblement la qualit&eacute; de vie. Quelques mod&egrave;les de BOO et HBP existants utilisent des niveaux physiologiques des hormones associ&eacute;s &agrave; la progression de la maladie chez l&#39;homme en un organisme g&eacute;n&eacute;tiquement manipulable. Nous pr&eacute;sentons un mod&egrave;le de BPH et BOO chez des souris avec la testost&eacute;rone (T) et de 17&beta;-estradiol (E(2)). Les souris m&acirc;les ont &eacute;t&eacute; implant&eacute;s chirurgicalement avec lib&eacute;ration lente sc granul&eacute;s contenant 25 T et 2,5 mg e (T+E(2)). Apr&egrave;s 2 et 4 mois de traitement hormonal, nous avons &eacute;valu&eacute; les patrons mictions et examin&eacute; la morphologie et l&#39;histologie de la vessie, ur&egrave;tre et de la prostate. Les souris trait&eacute;es avec T+E(2) d&eacute;velopp&eacute; des vessies significativement plus gros que les souris non trait&eacute;es, compatibles avec BOO. Des souris trait&eacute;es avec T+E(2) eu des complications sous forme d&#39;hypertrophie de la vessie, diverticules, calculs et &eacute;ventuelle d&eacute;compensation avec hydron&eacute;phrose. Traitement hormonal a entra&icirc;n&eacute; une diminution significative de la taille de la lumi&egrave;re ur&eacute;trale, a augment&eacute; la masse la prostate et a augment&eacute; le nombre de canaux prostatiques associ&eacute;e &agrave; l&#39;ur&egrave;tre prostatique, par rapport aux souris non trait&eacute;es. Invalidation d&#39;un dysfonctionnement a &eacute;t&eacute; observ&eacute;e chez les souris trait&eacute;es avec T+E(2), qui exposa gouttelette invalidation jacquard significativement diminu&eacute; masse Sub Sub br&egrave;ves et moins vides soutenues. La constellation d&#39;anomalies de voies urinaires inf&eacute;rieurs, y compris BOO, &eacute;largie de la prostate, et annulation de dysfonction observ&eacute;e chez les souris m&acirc;les trait&eacute;s avec T+E(2) est compatible avec HBP chez les hommes. Ce mod&egrave;le est adapt&eacute; pour une meilleures compr&eacute;hension des m&eacute;canismes mol&eacute;culaires et de l&#39;&eacute;laboration de nouvelles strat&eacute;gies pour traiter l&#39;HBP et BOO.

Testost&eacute;rone et estradiol-17&beta; induisent la croissance prostatique glandulaire, obstruction de la vessie prise et mictions dysfonctionnement chez les souris m&acirc;les.

Iperplasia prostatica benigna (BPH) e ostruzione del collo vescicale (BOO) sono comuni negli uomini anziani e possono contribuire ai sintomi del tratto urinario inferiori che hanno un impatto significativamente la qualit&agrave; della vita. Alcuni modelli esistenti di BOO e BPH utilizzano livelli fisiologici di ormoni associati con la progressione della malattia negli esseri umani in un organismo geneticamente manipolabile. Vi presentiamo un modello di BPH e BOO indotta nei topi con testosterone (T) e 17 &beta;-estradiolo (E(2)). Topi maschi sono stati impiantati chirurgicamente con rilascio lento sc pellet contenente 25 T e 2,5 mg E(2) (T+E(2)). Dopo 2 e 4 mesi di trattamento ormonale, abbiamo valutato pattern minzionale ed esaminato il lordo morfologia e istologia della vescica, uretra e della prostata. Topi trattati con T+E(2) sviluppato vesciche significativamente maggiore rispetto ai topi non trattati, coerenti con BOO. Alcuni topi trattati con T+E(2) avevano complicazioni in forma di ipertrofia della vescica, diverticoli, calcoli ed eventuale scompenso con idronefrosi. Trattamento ormonale causato una significativa riduzione delle dimensioni del lume uretra, aumentata la massa della prostata e aumentato numero di dotti prostatiche associata con l&#39;uretra prostatica, rispetto ai topi non trattati. La disfunzione minzionale &egrave; stata osservata nei topi trattati con T+E(2), che hanno esposto gocciolina minzionale pattern con significativamente diminuita massa Sub, durata Sub pi&ugrave; breve e meno sostenute vuoti. La costellazione di bassa anomalie delle vie urinarie, tra cui BOO, allargata prostates, e vista in topi maschi trattati con T+E(2) la disfunzione minzionale &egrave; coerenza con BPH negli uomini. Questo modello &egrave; adatto per meccanismi molecolari di migliore comprensione e per lo sviluppo di nuove strategie per affrontare BPH e BOO.

Testosterone e 17 &beta;-estradiolo induce la crescita ghiandolare prostatica, ostruzione del collo vescicale e disfunzione minzionale nei topi maschi.

Androgens and estrogens, acting via their respective receptors, are important in benign prostatic hyperplasia (BPH). The goals of this study were to quantitatively characterize the tissue distribution and staining intensity of androgen receptor (AR) and estrogen receptor-alpha (ERÎ±), and assess cells expressing both AR and ERÎ±, in human BPH compared to normal prostate. A tissue microarray composed of normal prostate and BPH tissue was used and multiplexed immunohistochemistry was performed to detect AR and ERÎ±. We used a multispectral imaging platform for automated scanning, tissue and cell segmentation and marker quantification. BPH specimens had an increased number of epithelial and stromal cells and increased percentage of epithelium. In both stroma and epithelium, the mean nuclear area was decreased in BPH relative to normal prostate. AR expression and staining intensity in epithelial and stromal cells was significantly increased in BPH compared to normal prostate. ERÎ± expression was increased in BPH epithelium. However, stromal ERÎ± expression and staining intensity was decreased in BPH compared to normal prostate. Double positive (AR and ERÎ±) epithelial cells were more prevalent in BPH, and fewer double negative (AR and ERÎ±) stromal and epithelial negative cells were observed in BPH. These data underscore the importance of tissue layer localization and expression of steroid hormone receptors in the prostate. Understanding the tissue-specific hormone action of androgens and estrogens will lead to a better understanding of mechanisms of pathogenesis in the prostate and may lead to better treatment for BPH.

ArticleTotal : 2	Year
Publication title Cited by 13	2013
Publication title Cited by 2	2019

Article	Year
Androgens and estrogens in benign prostatic hyperplasia: past, present and future. Differentiation; research in biological diversity\| PubMed ID: 21620560	2011
Pelvic angiomyolipoma. Urology\| PubMed ID: 21722945	2012
Renal trauma from recreational accidents manifests different injury patterns than urban renal trauma. The Journal of urology\| PubMed ID: 22591969	2012
Testosterone and 17Î²-estradiol induce glandular prostatic growth, bladder outlet obstruction, and voiding dysfunction in male mice. Endocrinology\| PubMed ID: 22948219	2012
Sex steroid receptor expression and localization in benign prostatic hyperplasia varies with tissue compartment. Differentiation; research in biological diversity\| PubMed ID: 23792768	2013

Tristan M. Nicholson

Biography

JoVE Journal Publications

Other Publications