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Prostate Gland (prostate + gland)
Selected AbstractsSpontaneous mutation in mice provides new insight into the genetic mechanisms that pattern the seminal vesicles and prostate glandDEVELOPMENTAL DYNAMICS, Issue 4 2003Paul C. Marker Abstract The seminal vesicles and prostate gland are anatomically adjacent male sex-accessory glands. Although they arise from different embryonic precursor structures and express distinct sets of secretory proteins, these organs share common features in their developmental biology. A key shared developmental feature is the elaboration of complex secretory epithelia with tremendous surface area from simple precursor structures with juxtaposed epithelial and mesenchymal cells. In this study, new insight into the nature of the biological processes that underlie glandular morphogenesis is achieved by analyzing the phenotypes present in mice that harbor a spontaneous mutation, seminal vesicle shape (svs), previously identified for causing altered seminal vesicle morphology in adults. An examination of seminal vesicle development in svs mice provides the first evidence that the concurrent processes of epithelial branching and epithelial infolding are distinct processes under separate genetic control. It also provides the first direct evidence that the thickness and topology of the smooth muscle layer in the seminal vesicles are determined by interaction with the glandular epithelium during the branching process. In addition, the seminal vesicle phenotype in svs mice is shown to phenocopy the morphologic form present in certain other mammals such as the guinea pig, raising the possibility that the svs mutation is the sort of variant that arises during evolution. By also including an investigation of the prostate gland, this study also identifies previously unrecognized phenotypes in svs prostates, including increased gland size and dramatically reduced levels of branching morphogenesis. Finally, this study advances the goal of identifying the svs gene by mapping the svs mutation relative to known molecular markers and testing Fgfr2 as a candidate gene. The finding that the svs mutation maps to a genomic region syntenic to a region frequently deleted in human prostate tumors, together with the prostatic phenotype present in svs mice, further raises the interesting possibility that the svs mutation will identify a candidate prostate tumor suppressor gene. Developmental Dynamics 226:643,653, 2003. © 2003 Wiley-Liss, Inc. [source] Multiple sites of L-histidine decarboxylase expression in mouse suggest novel developmental functions for histamineDEVELOPMENTAL DYNAMICS, Issue 1 2001Kaj Karlstedt Abstract Histamine mediates many types of physiologic signals in multicellular organisms. To clarify the developmental role of histamine, we have examined the developmental expression of L-histidine decarboxylase (HDC) mRNA and the production of histamine during mouse development. The predominant expression of HDC in mouse development was seen in mast cells. The HDC expression was evident from embryonal day 13 (Ed13) until birth, and the mast cells were seen in most peripheral tissues. Several novel sites with a prominent HDC mRNA expression were revealed. In the brain, the choroid plexus showed HDC expression at Ed14 and the raphe neurons at Ed15. Close to the parturition, at Ed19, the neurons in the tuberomammillary (TM) area and the ventricular neuroepithelia also displayed a clear HDC mRNA expression and histamine immunoreactivity (HA-ir). From Ed14 until birth, the olfactory and nasopharyngeal epithelia showed an intense HDC mRNA expression and HA-ir. In the olfactory epithelia, the olfactory receptor neurons (ORN) were shown to have very prominent histamine immunoreactivity. The bipolar nerve cells in the epithelium extended both to the epithelial surface and into the subepithelial layers to be collected into thick nerve bundles extending caudally toward the olfactory bulbs. Also, in the nasopharynx, an extensive subepithelial network of histamine-immunoreactive nerve fibers were seen. Furthermore, in the peripheral tissues, the degenerating mesonephros (Ed14) and the convoluted tubules in the developing kidneys (Ed15) showed HDC expression, as did the prostate gland (Ed15). In adult mouse brain, the HDC expression resembled the neuronal pattern observed in rat brain. The expression was restricted to the TM area in the ventral hypothalamus, with the main expression in the five TM subgroups called E1,E5. A distinct mouse HDC mRNA expression was also seen in the ependymal wall of the third ventricle, which has not been reported in the rat. The tissue- and cell-specific expression patterns of HDC and histamine presented in this work indicate that histamine could have cell guidance or regulatory roles in development. © 2001 Wiley-Liss, Inc. [source] Vitamin D and calcium deficits predispose for multiple chronic diseasesEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 5 2005M. Peterlik Abstract There is evidence from both observational studies and clinical trials that calcium malnutrition and hypovitaminosis D are predisposing conditions for various common chronic diseases. In addition to skeletal disorders, calcium and vitamin D deficits increase the risk of malignancies, particularly of colon, breast and prostate gland, of chronic inflammatory and autoimmune diseases (e.g. insulin-dependent diabetes mellitus, inflammatory bowel disease, multiple sclerosis), as well as of metabolic disorders (metabolic syndrome, hypertension). The aim of the present review was to provide improved understanding of the molecular and cellular processes by which deficits in calcium and vitamin D cause specific changes in cell and organ functions and thereby increase the risk for chronic diseases of different aetiology. 1,25-dihydroxyvitamin D3 and extracellular Ca++ are both key regulators of proliferation, differentiation and function at the cellular level. However, the efficiency of vitamin D receptor-mediated intracellular signalling is limited by the negative effects of hypovitaminosis D on extrarenal 25-hydroxyvitamin D-1,-hydroxylase activity and thus on the production of 1,25-dihydroxyvitamin D3. Calcium malnutrition eventually causes a decrease in calcium concentration in extracellular fluid compartments, resulting in organ-specific modulation of calcium-sensing receptor activity. Hence, attenuation of signal transduction from the ligand-activated vitamin D receptor and calcium-sensing receptor seems to be the prime mechanism by which calcium and vitamin D insufficiencies cause perturbation of cellular functions in bone, kidney, intestine, mammary and prostate glands, endocrine pancreas, vascular endothelium, and, importantly, in the immune system. The wide range of diseases associated with deficits in calcium and vitamin D in combination with the high prevalence of these conditions represents a special challenge for preventive medicine. [source] The expression of glutathione reductase in the male reproductive system of rats supports the enzymatic basis of glutathione function in spermatogenesisFEBS JOURNAL, Issue 5 2002Tomoko Kaneko Glutathione reductase (GR) recycles oxidized glutathione (GSSG) by converting it to the reduced form (GSH) using an NADPH as the electron source. The function of GR in the male genital tract of the rat was examined by measuring its enzymatic activity and examining the gene expression and localization of the protein. Levels of GR activity, the protein, and the corresponding mRNA were the highest in epididymis among testes, vas deferens, seminal vesicle, and prostate gland. The localization of GR, as evidenced by immunohistochemical techniques, reveals that it exists at high levels in the epithelia of the genital tract. In testis, GR is mainly localized in Sertoli cells. The enzymatic activity and protein expression of GR in primary cultured testicular cells confirmed its predominant expression in Sertoli cells. Intracellular GSH levels, expressed as mol per mg protein, was higher in spermatogenic cells than in Sertoli cells. As a result of these findings, the effects of buthionine sulfoximine (BSO), an inhibitor for GSH synthesis, and 1,3-bis(2-chlorethyl)-1-nitrosourea (BCNU), an inhibitor for GR, on cultured testicular cells were examined. Sertoli cells were prone to die as the result of BCNU, but not BSO treatment, although intracellular levels of GSH declined more severely with BSO treatment. Spermatogenic cells were less sensitive to these agents than Sertoli cells, which indicates that the contribution of these enzymes is less significant in spermatogenic cells. The results herein suggest that the GR system in Sertoli cells is involved in the supplementation of GSH to spermatogenic cells in which high levels of cysteine are required for protamine synthesis. In turn, the genital tract, the epithelia of which are rich in GR, functions in an antioxidative manner to protect sulfhydryl groups and unsaturated fatty acids in spermatozoa from oxidation during the maturation process and storage. [source] Biofilms in chronic bacterial prostatitis (NIH-II) and in prostatic calcificationsFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 3 2010Sandra Mazzoli Abstract The prevalence of inflammatory conditions of the prostate gland is increasing. In Italy, there is a high incidence of prostatitis (13.3%), also accompanied by prostatic calcifications. Cat NIH-II chronic bacterial prostatitis (CBPs) are the most frequent. Their aetiology theoretically involves the whole range of bacterial species that are able to form biofilms and infect prostate cells. The aim of our study was to isolate potential biofilm-producing bacteria from CBP patients, to evaluate their ability to produce in vitro biofilms, and to characterize intraprostatic bacteria and prostatic calcifications using scanning electron microscopy. The 150 clinical bacterial strains isolated from chronic prostatitis NIH-II patients were: 50 Enterococcus faecalis; 50 Staphylococcus spp.; 30 Escherichia coli; 20 gram-negative miscellanea. Quantitative assay of biofilm production and adhesion was performed according to the classic Christensen microwell assay. Isolates were classified as nonproducers, weak, moderate or strong producers. The majority of E. coli, gram-negative bacteria, Staphylococci and Enterococci strains were strong or medium producers: 63,30%, 75,15%, 46,36%, and 58,14%, respectively. Prostatic calcifications consisted of bacteria-like forms similar to the species isolated from biological materials and calcifications of patients. Our study proves, for the first time, that bacterial strains able to produce biofilms consistently are present in CBP. Additionally, prostatic calcifications are biofilm-related. [source] Amplification and overexpression of prosaposin in prostate cancerGENES, CHROMOSOMES AND CANCER, Issue 4 2005Shahriar Koochekpour We identified prosaposin (PSAP) as a secreted protein expressed in androgen-independent (AI) prostate cancer cells by cloning/sequencing, after probing a PC-3 cDNA library expressed in the ,TriplEx phagemid expression vector with a polyclonal rabbit antibody generated against pooled human seminal plasma. PSAP is a neurotrophic molecule; its deficiency or inactivation has proved to be lethal in man and mice, and in mice, it leads to abnormal development and atrophy of the prostate gland, despite normal testosterone levels. We used Southern hybridization, quantitative real-time polymerase chain reaction, and/or single nucleotide polymorphism (SNP) array analysis, and we now report the genomic amplification of PSAP in the metastatic AI prostate cancer cell lines, PC-3, DU-145, MDA-PCa 2b, M-12, and NCI-H660. In addition, by using SNP arrays and a set of 25 punch biopsy samples of human prostate cancer xenografts (LAPC3, LuCaP 23.1, 35, 49, 58, 73, 77, 81, 86.2, 92.1, 93, 96, 105, and 115), lymph nodes, and visceral-organ metastases, we detected amplification of the PSAP locus (10q22.1) in LuCaP 58 and 96 xenografts and two lymph node metastases. In addition, AI metastatic prostate cancer cell lines C4-2B and IA8-ARCaP over-expressed PSAP mRNA without evidence of genomic amplification. Taken together with prior data that demonstrated the growth-, migration-, and invasion-promoting activities, the activation of multiple signal transduction pathways, and the antiapoptotic effect of PSAP (or one of its active domains, saposin C) in prostate cancer cells, our current observation of PSAP amplification or overexpression in prostate cancer suggests, for the first time, a role for this molecule in the process of carcinogenesis or cancer progression in the prostate. © 2005 Wiley-Liss, Inc. [source] A neglected gland: a review of Cowper's glandINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 2 2005BILAL CHUGHTAI Summary Cowper's glands are pea sized glands present inferior to the prostate gland in the male reproductive system. They produce thick clear mucus prior to ejaculation that drains into the spongy urethra. Though it is well established that the function of the Cowper's gland secretions is to neutralize traces of acidic urine in the urethra, knowledge regarding the various lesions and associated complications of this gland is scarce. This review provides a comprehensive report on the development, function and various lesions associated with Cowper's gland. [source] In vivo MR elastography of the prostate gland using a transurethral actuatorMAGNETIC RESONANCE IN MEDICINE, Issue 3 2009Rajiv Chopra Abstract Conventional approaches for MR elastography (MRE) using surface drivers have difficulty achieving sufficient shear wave propagation in the prostate gland due to attenuation. In this study we evaluate the feasibility of generating shear wave propagation in the prostate gland using a transurethral device. A novel transurethral actuator design is proposed, and the performance of this device was evaluated in gelatin phantoms and in a canine prostate gland. All MRI was performed on a 1.5T MR imager using a conventional gradient-echo MRE sequence. A piezoceramic actuator was used to vibrate the transurethral device along its length. Shear wave propagation was measured transverse and parallel to the rod at frequencies between 100 and 250 Hz in phantoms and in the prostate gland. The shear wave propagation was cylindrical, and uniform along the entire length of the rod in the gel experiments. The feasibility of transurethral MRE was demonstrated in vivo in a canine model, and shear wave propagation was observed in the prostate gland as well as along the rod. These experiments demonstrate the technical feasibility of transurethral MRE in vivo. Further development of this technique is warranted. Magn Reson Med, 2009. © 2009 Wiley-Liss, Inc. [source] 3T MR of the prostate: Reducing susceptibility gradients by inflating the endorectal coil with a barium sulfate suspensionMAGNETIC RESONANCE IN MEDICINE, Issue 5 2007Yael Rosen Abstract Most prostate MRI/MRS examinations are performed with an endorectal coil inflated with air, leading to an air,tissue interface that induces magnetic susceptibility gradients within the gland. Inflation of the coil with a barium sulfate suspension is described and compared to inflation with air or liquid perfluorocarbon (PFC). The B0 field in the prostate gland was mapped for five healthy volunteers when the endorectal coil was inflated with each of the three agents. A marked decrease in the posterior-anterior (P-A) field gradient and a significant improvement in field homogeneity were evident in the presence of a barium suspension and PFC relative to air. MRS data acquired from the prostate gland in the presence of air, PFC, and a barium suspension in the endorectal coil showed similar trends, demonstrating improvement in line-widths and spectral resolution when the barium suspension or the PFC were inflating the endorectal coil. On this basis we conclude that a barium suspension provides an available, cheap, and safe alternative to PFC, and we suggest that inflating the endorectal coil with a barium suspension should be considered for prostate MR studies, especially at high field strengths (such as 3T). Magn Reson Med 57:898,904, 2007. © 2007 Wiley-Liss, Inc. [source] Conventional prostatic adenocarcinoma arising in a multilocular prostatic cystadenomaPATHOLOGY INTERNATIONAL, Issue 5 2010Thomas K. Lee Multilocular prostatic cystadenoma is a rare benign neoplasm located between the bladder and the rectum. These are prostatic tissue and have been shown to harbor high-grade intraepithelial neoplasia and likely susceptible to the same disease processes seen in the prostate gland. We report the first case of conventional prostatic adenocarcinoma involving a multilocular cystadenoma. Distinction from cystadenocarcinoma is also made. [source] Effect of Mucuna urens (horse eye bean) on the gonads of male guinea-pigsPHYTOTHERAPY RESEARCH, Issue 2 2001Paul Udoh Abstract The effect of Mucuna urens (seeds) on the gonads and sex accessory glands of male guinea-pigs was investigated. Sexually mature guinea-pigs of proven fertility were administered orally with 70,mg/kg and 140,mg/kg body weight of crude extract daily for 8 weeks respectively. Phytochemical screening of the seeds revealed the presence of alkaloids. No death or weight loss were observed during the duration of treatment. No pregnancy occurred in females mated with the treated males. Histological observations at high dose (140,mg/kg) showed complete degeneration of sperm in the testicular tubules. In some tubules, the acrosomal cap of the sperm cells was separated from the nuclei which underwent colour changes. In some tubules only the tails were left in the lumen. The spermatids, primary and secondary spermatocytes showed pycnosis while the morphology of spermatogonia and germinal epithelium appeared normal. Some epididymides were devoid of sperm while others contained degenerated spermatozoa and cell debris. In the prostate gland there was collapse of the villi and reduction of secretion in both the prostate and seminal vesicles. At low doses (70,mg/kg), there was spermatogenic arrest at spermatid stage. These observations have shown that M. urens is a potential male antifertility agent. Copyright © 2001 John Wiley & Sons, Ltd. [source] The ageing male reproductive tract,THE JOURNAL OF PATHOLOGY, Issue 2 2007N Sampson Abstract Ageing of the male reproductive system is characterized by changes in the endocrine system, hypogonadism, erectile dysfunction and proliferative disorders of the prostate gland. Stochastic damage accumulating within ageing leads to progressive dysregulation at each level of the hypothalamic,pituitary,gonadal (HPG) axis and in local auto/paracrine interactions, thereby inducing morphological changes in reproductive target organs, such as the prostate, testis and penis. Despite age-related changes in the HPG axis, endocrine functions are generally sufficient to maintain fertility in elderly men. Ageing of the male reproductive system can give rise to clinically relevant manifestations, such as benign prostatic hyperplasia (BPH), prostate cancer (PCa) and erectile dysfunction (ED). In this review, we discuss morphological/histological changes occurring in these organs and current views and concepts of the underlying pathology. Moreover, we emphasize the molecular/cellular pathways leading to reduced testicular/penile function and proliferative disorders of the prostate gland. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Characterization of Phosphodiesterase Type 5 Expression and Functional Activity in the Human Male Lower Urinary TractTHE JOURNAL OF SEXUAL MEDICINE, Issue 1pt1 2010Benedetta Fibbi MD ABSTRACT Introduction., Phosphodiesterase type 5 (PDE5) inhibitors ameliorate low urinary tract (LUT) symptoms in men with ED and symptomatic benign prostatic hyperplasia (BPH). PDE5 is highly expressed in rat and human bladder, where it regulates cyclic guanosine monophosphate (cGMP) degradation, muscle tone, and proliferation. Aim., To investigate PDE5 tissue distribution and activity in human LUT tissues (urethra, prostate, and bladder). Main Outcome Measures., PDE5 expression and activity were analyzed and compared within the same BPH patient in LUT tissues and in smooth muscle cells (SMCs) cultured from urethra, prostate, and bladder. Methods., In LUT tissues, PDE5 was localized by immunohistochemistry and mRNA expression by quantitative real-time polymerase chain reaction. Proliferation assay was used as readout of PDE5 activity, evaluated as ability of vardenafil to increase the antiproliferative effect of different nitric oxide (NO)/cGMP pathway activators [the PDE5-resistant cGMP analog Sp-8-Br-PET-cGMPS, the NO donor sodium nitroprusside (SNP), and the soluble guanylate cyclase (sGC) stimulator BAY 41-8543]. Results., In all the LUT tissues, PDE5 was immunolocalized in blood vessels and in muscular fibres, but not in epithelium. PDE5 mRNA expression was higher in urethra and bladder than in prostate SMC. The antiproliferative effect of Sp-8-Br-PET-cGMPS was similar in all LUT SMC. In prostatic SMC, SNP and BAY 41-8543 show a dose-dependent antiproliferative effect that resulted marginally enhanced by vardenafil. Conversely, in urethra and bladder SMC the antiproliferative effect of SNP and BAY 41-8543 was lower than in prostatic SMC, but it was significantly enhanced by vardenafil. In urethral and bladder cells vardenafil half-maximal response inhibiting concentration was in the subnanomolar range, whereas in prostate cells it resulted significantly higher. Conclusions., The highest expression and biological activity of PDE5 was found in bladder. However, a consistent PDE5 expression and activity was also found in prostatic urethra. In contrast, the prostate gland showed the lowest PDE5 abundance and cultures derived from this tissue were less sensitive to vardenafil. Fibbi B, Morelli A, Vignozzi L, Filippi S, Chavalmane A, De Vita G, Marini M, Gacci M, Vannelli GB, Sandner P, and Maggi M. Characterization of phosphodiesterase type 5 expression and functional activity in the human male lower urinary tract. J Sex Med 2010;7:59,69. [source] JunD mediates androgen-induced oxidative stress in androgen dependent LNCaP human prostate cancer cells,THE PROSTATE, Issue 9 2008Farideh Mehraein-Ghomi Abstract BACKGROUND Numerous and compelling evidence shows that high level of reactive oxygen species (ROS) plays a key role in prostate cancer occurrence, recurrence and progression. The molecular mechanism of ROS overproduction in the prostate gland, however, remains mostly unknown. Unique AP-1 transcription factor JunD has been shown to inhibit cell proliferation, promote differentiation and mediate stress responses in a variety of eukaryotic cells. We previously reported that androgen,androgen receptor induced ROS production in androgen-dependent LNCaP human prostate cancer cells is associated with increased JunD level/AP-1 transcriptional activity. METHODS LNCaP cells constitutively overexpressing a functionally inactive form of JunD (JunD,TA) or stably transfected with JunD siRNA (siJunD) to suppress JunD protein expression were established. Overexpression of JunD in LNCaP cells using transient transfection method was applied to assess the induction of ROS production in LNCaP cells. DCF assay was used to measure the ROS concentrations in the transfected as well as non-transfected control cells. RT-PCR and Western blot analyses were used to confirm silencing or overexpression of JunD in the transfected cells. RESULTS In the absence of androgen, LNCaP cells transiently transfected with a JunD overexpressing vector have relatively enhanced cellular ROS levels as compared to LNCaP cells transfected with a vector control. LNCaP cells that fail to express functional JunD (JunD,TA or siJunD) do not exhibit any increase in ROS production in response to androgen. CONCLUSION Based on these data, we conclude that JunD is an essential mediator of the androgen-induced increase in ROS levels in LNCaP cells. Prostate 68:924,934, 2008. © 2008 Wiley-Liss, Inc. [source] Inhibition of protein kinase CK2 leads to a modulation of androgen receptor dependent transcription in prostate cancer cellsTHE PROSTATE, Issue 2 2007Claudia Götz Abstract BACKGROUND The androgen receptor (AR) mediates the biological responses of androgens in the prostate gland. In prostate cancer, this pathway is often deregulated and causes an uncontrolled proliferation. METHODS The current study focuses on the effects of an inhibition of protein kinase CK2 on the AR-mediated transcription in LNCaP prostate cancer cells. We used chemical inhibitors of CK2 as well as dominant-negative kinase mutants to downregulate the CK2 activity. We determined the effects of the inhibition by Western blot analysis of endogenous target genes of the AR as well as by reporter assays. RESULTS We found that inhibition of CK2 led to a downregulation of the AR-dependent transcription. Moreover, the amount of the AR protein decreased significantly. CONCLUSION According to the fact that AR pathways are involved in the development and progression of prostate cancer, the ability to modulate AR function should provide an alternative basis for the development of new cancer therapies. Prostate © 2006 Wiley-Liss, Inc. [source] Immunohistochemical detection of cysteine-rich secretory protein 3 in tissue and in serum from men with cancer or benign enlargement of the prostate glandTHE PROSTATE, Issue 6 2006Anders Bjartell Abstract BACKGROUND Recently, the gene for cysteine-rich secretory protein 3 (CRISP-3) was reported to be highly upregulated in prostate cancer (PCa) compared to benign prostatic tissue. The current aims were to investigate diagnostic use of tissue expression and immunodetection in serum of CRISP-3 for detection or monitoring of PCa. METHODS Radical prostatectomy specimens and tissue microarrays from transurethral resections and metastases were analyzed for CRISP-3 and PSA by immunohistochemistry. CRISP-3 in tissue homogenates and in serum was measured by an in-house ELISA and PSA by a commercially available immunoassay. RESULTS Immunostaining for CRISP-3 in benign prostatic epithelium was generally weak or not detectable. Specific and strong immunostaining was found in a major proportion of cells in high-grade prostatic-intraepithelial-neoplasia (HG-PIN,12/17 patients), in most primary tumors (111/115), and in lymph node (11/15) and bone (12/15) metastases. CRISP-3 immunostaining intensity was regularly strong in areas of Gleason grades 4/5, where PSA-immunoreaction was less intense. Serum levels of CRISP-3 were not different in patients with PCa (n,=,152) compared to men with BPH (n,=,81). There was a very weak co-variation between levels of CRISP-3 versus PSA in serum from PCa patients (P,<,0.05). After orchiectomy, levels of CRISP-3 in serum decreased in median with 11% compared to a 97% median decrease of PSA in serum from 15/20 patients with advanced PCa. CONCLUSIONS Strong immunostaining for CRISP-3 is common in HG-PIN and preserved in most PCa specimens, which warrant further immunohistochemical studies of CRISP-3 in PCa. Serum levels of CRISP-3 do not primarily reflect PCa. Prostate 66:591,603, 2006. © 2005 Wiley-Liss, Inc. [source] Constitutive activation of PI3K-Akt and NF-,B during prostate cancer progression in autochthonous transgenic mouse modelTHE PROSTATE, Issue 3 2005Sanjeev Shukla Abstract BACKGROUND Cancer progression is usually facilitated by independent growth signals that may lead to increased cell survival and evasion of apoptosis. Phosphatidylinositol 3,-OH kinase (PI3K)-Akt and transcription factor NF-,B are important signaling molecules and key survival factors involved in the control of cell proliferation, apoptosis, and oncogenesis. Although PI3K-Akt and NF-,B have been implicated in the development and progression of prostate cancer, expression of these molecules during progression of autochthonous disease has not been elucidated. METHODS Prostate cancer growth and progression in autochthonous transgenic adenocarcinoma of the mouse prostate (TRAMP) mice and male non-transgenic littermates were observed by magnetic resonance imaging (MRI). Expression patterns of PI3K-Akt, NF-,B, I,B, and associated signaling molecules during different stages of cancer progression in these mice were examined by Western blot analysis, electrophoretic mobility shift assay (EMSA), enzyme-linked immunoabsorbent assay (ELISA), kinase assay, and immunohistochemistry. RESULTS Sequential MRI and gross analysis of prostate gland exhibited increasing prostate volume associated with the development and progression of prostatic adenocarcinoma in TRAMP mice, compared to male non-transgenic littermates. Differential protein expression of PI3K, phosphorylated-Akt (Ser473), I,B, and its phosphorylation, IKK kinase activity, NF-,B/p65, p50, DNA binding, and transcriptional-regulated genes, viz., Bcl2, cyclin D1, MMP-9, and VEGF were observed during prostate cancer progression in TRAMP mice, compared to male non-transgenic littermates. Expressions of these molecules were significantly increased during cancer progression observed at 24 and 32 weeks of age. CONCLUSIONS Differential expression pattern of PI3K-Akt, NF-,B and I,B during prostate cancer progression in TRAMP mice suggest that these molecules represent potential molecular targets for prevention and/or therapeutic intervention. © 2005 Wiley-Liss, Inc. [source] Heterogeneous gene methylation patterns among pre-invasive and cancerous lesions of the prostate: A histopathologic study of whole mount prostate specimensTHE PROSTATE, Issue 1 2004Karen Woodson Abstract BACKGROUND Gene methylation may contribute to prostate carcinogenesis through the silencing of gene transcription. We report on the methylation status of several genes shown to be silenced at different stages of progression using whole mount prostate specimens and laser capture microdissection. This is the first study to evaluate gene methylation patterns across multiple pre-cancerous and invasive cancer foci from the same prostate gland. METHODS Real-time PCR was used to evaluate methylation of five genes (GSTP1, RASSF1A, RAR,2, CD44, and EDNRB) across normal epithelium, high-grade prostatic intraepithelial neoplasia (HGPIN), and multiple tumor foci from each of 11 prostate cancer patients. RESULTS Gene methylation was not found in normal epithelium. To our knowledge, this is the first report of RASSF1A and RAR,2 methylation in HGPIN lesions (30% prevalence for each gene). In addition, RASSF1A, RAR,2, and GSTP1 methylation was highly prevalent in tumor foci (>75% for all three genes). Methylation of CD44 and EDNRB was observed in 41 and 38% of tumors but was not present in HGPIN. CONCLUSIONS These data suggest that genes may be methylated at different points in the histopathologic progression of prostate cancer and these differences can be found in various histologic foci from the same gland. © 2004 Wiley-Liss, Inc. [source] Interstitial cells in the human prostate: A new therapeutic target?THE PROSTATE, Issue 4 2003Frank Van der Aa Abstract BACKGROUND Interstitial cells have been described in different human organs, including gut and bladder. In the gut they function as pacemaker cells, generating slow wave potentials. Absence or defects in these cells result in motility disorders. In the bladder these cells express the vanilloid receptor and may contribute to the working mechanism of vanilloid therapy. Recently, slow wave potentials and interstitial cells were described in the guinea-pig prostate. In this study we describe the presence of interstitial cells in the human prostate gland. METHODS We performed immunohistochemical staining for c-kit, vanilloid receptor (VR1), cannabinoid receptor (CB1) connexin43, and neurofilament on fresh frozen tissue from 14 prostatectomy specimens. RESULTS A large number of cells with a stellate aspect were noticed under the basal layer of the prostatic duct system and in between the smooth muscle cells. They were immunoreactive for c-kit, VR1, and connexin43 but not to CB1 or neurofilament. CONCLUSIONS There is evidence for interstitial cells in the human prostate. Taken together their topography and immunohistochemical characterization, the discovery of slow wave potentials in guinea pig prostate and the knowledge of interstitial cells in other organs, interstitial cells are likely to be involved in normal prostate physiology. Prostate 56: 250,255, 2003. © 2003 Wiley-Liss, Inc. [source] The Gross and Micro Anatomy of the Accessory Sex Glands of the Male Agouti (Dasyprocta leporina)ANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 3 2009W. M. Mollineau Summary This study was a follow up to the study on the gross anatomy of the male agouti (Dasyprocta leporina) reproductive system. The seminal vesicles of the agouti are lobulated structures. The mean diameter of the large lumen is 883.6 ± 76.83 ,m. The mucosa (24.1 ± 0.92 ,m), which is lined by pseudo-stratified columnar epithelium is thrown into folds, which often branch. The lamina muscularis mucosa is thin and is made of loose connective tissue containing blood vessels. The mucosa of the leaf-like coagulating glands of the agouti is folded. The mean diameter of the lumen is 488.3 ± 41.96 ,m. The mucosa contains tubuloalveolar glands, which have a mean length of 199.5 ± 28.83 ,m. The thin epithelium, 15.0 ± 1.25-,m wide, consists mostly of pseudo-stratified columnar cells. The epithelium also has surface modifications in the form of apical blebs and cilia. The epithelium of the agouti's lobulated prostate gland is also folded creating a large lumen with a mean diameter of 995.5 ± 55.70 ,m. The mucosa contains tubular and tubuloalveolar glands, each having a mean length of 134.4 ± 13.59 ,m. The epithelium (13.9 ± 1.16 ,m) consists of pseudo-stratified columnar cells. The pea-shaped bulbourethral gland (BG) of the agouti consists of convoluted tubular, mucous secretory units, which are irregularly shaped each with a mean length of 177.9 ± 7.10 ,m and a mean width of 63.5 ± 3.97 ,m. The BG of the agouti are ventro-lateral to the rectum and dorsally positioned to the pubic symphysis, and connected to the urethra by short ducts. [source] Investigational New Drug-Directed Toxicology and Pharmacokinetic Study of 4-[3-(2-Nitro-1-Imidazolyl)-Propylamino]-7-Chloroquinoline Hydrochloride (NLCQ-1, NSC 709257) in Beagle DogsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 6 2010Maria V. Papadopoulou The present study is one of several pre-clinical toxicology studies conducted in support of an ,investigational new drug' (IND) application to test this agent as an adjuvant to radio/chemotherapy for the treatment of cancer in humans. Twenty-four dogs were each assigned to one vehicle control group or to one of three test article-treated groups (three dogs/sex/treatment group). Intravenous (i.v.) doses of 0, 2.74, 5.48 and 10.95 mg/kg/day (54.8, 109.6 or 219 mg/m2/day) were administered on a per day × 5 days (qd × 5) schedule. NLCQ-1 was formulated as a solution in sterile saline at 1.5 mg/ml. None of the dogs died during this 33-day study. With few exceptions, most of the clinical signs of toxicity were noted within 2 hr following dosing in the 10.95 mg/kg/day dose group. These observations included aggressive behaviour, ataxia, tachypnea, emesis, hypoactivity, excessive salivation, tremors, and involuntary urination and defecation. Aggressive behaviour was judged to be dose-limiting. No clinical signs of toxicity were noted during the 28-day observation period that followed the 5-day dose period. Findings in a functional observation battery examination were consistent with the clinical observations. No drug-related effects were noted on the body weight or food consumption values, and no drug-related changes were noted during ocular examinations made on these animals prior to scheduled necropsy or during examination of electrocardiogram recordings made at 15 min. and 2 hr after dosing on days 1 and 5. No definitive changes in haematology, clinical chemistry or coagulation values were noted in dogs treated with NLCQ-1. NLCQ-1 was detected in the plasma of treated dogs on days 1 and 5, up to 60 min. after dosing (2.74 and 5.48 mg/kg/day) and up to 8 hr after dosing (10.95 mg/kg/day). There was a dose-related increase in maximum plasma concentration of NLCQ-1 at 5 min. after dosing; comparable concentrations were noted on days 1 and 5. No definitive test article-related lesions were noted during microscopic evaluation of tissues from dogs in this study, although lesions noted at the injection site and in the vascular tissue, lungs, thymus, prostate gland, muscle, adrenal cortex and tongue may have resulted from treatment with this drug. Any drug-related toxicity noted was readily reversible and not cumulative. No sex difference was detected in the susceptibility to NLCQ-1-induced toxicity. [source] Diffusion properties of transurethral intraprostatic injectionBJU INTERNATIONAL, Issue 9 2004Mark K. Plante OBJECTIVES To evaluate the location and extent of diffusion that occurs when liquid is injected transurethrally into the prostate gland, by correlating real-time fluoroscopy and gross pathology, and to quantify the variables that influence intraprostatic diffusion during chemoablation of the prostate. MATERIALS AND METHODS A solution of diatrizoate meglumine (HypaqueTM, Nycomed, Princeton, NJ) gentamicin and methylene-blue dye (HGM) was injected transurethrally into the prostate in six dogs, using a passive-deflection needle injection system. The intraprostatic diffusion characteristics were evaluated during each injection using real-time C-arm fluoroscopy, and following each injection by gross examination of methylene blue staining within the prostatic tissues. HGM back-flow into the urethra at the time of injection was assessed by measuring gentamicin levels in the collected bladder irrigant after each injection, using a standard dilution formula. RESULTS There was variability in the intraprostatic diffusion both fluoroscopically and grossly. The needle occasionally assumed a straighter trajectory than its intended curve. Intraprostatic diffusion was detected in 12 of 36 injections (33%). Using standard manipulations of various devices increased the intraprostatic diffusion in these injections to almost 80%. There was less intraprostatic diffusion when the injection resistance was either extremely high or absent. There was no extraprostatic extravasation of HGM beyond the prostatic capsule. CONCLUSION Current methods of transurethral intraprostatic injection are variable for both the diffusion of HGM solution and in needle deployment. The gross diffusion patterns with the HGM solution were consistent with the diffusion patterns documented in our previous research using absolute ethanol. These and other factors may partly explain the variability of the lesions produced with ethanol injection. Therefore, more research is needed to further elucidate the diffusion characteristics of solutions injected intraprostatically using the transurethral approach. [source] Experimental Escherichia coli epididymitis in rats: a model to assess the outcome of antibiotic treatmentBJU INTERNATIONAL, Issue 9 2002M. Ludwig Objective ,To assess the effect of initial antimicrobial therapy with a new highly potent quinolone (sparfloxacin) on the outcome of infection, especially acute and chronic inflammation, in a rat model of unilateral Escherichia coli epididymitis. Materials and methods ,The study included 60 Sprague-Dawley rats, each of which received 0.1 mL of an E. coli (0:6 strain) suspension (106 colony forming units/mL) injected into the right ductus deferens. At 24 h after infection an oral antimicrobial treatment with sparfloxacin was initiated in half of the animals. The rats were killed 14 days, 3 and 6 months after infection, and both epididymes and the prostate gland cultured to re-isolate E. coli. To evaluate the grade of inflammation in both epididymes, histological variables, including acute and chronic inflammation and scar formation, were evaluated and a total inflammatory score, representing the sum of all variables, computed. Results ,Whereas antimicrobial therapy eradicated the pathogen, in untreated animals the pathogen was detectable for up to 6 months after infection in the infected epididymis and/or the prostate gland, while the contralateral epididymis was sterile. The inflammatory reaction in the infected epididymis was significantly less in treated animals (P < 0.001). Subclinical nonbacterial inflammation was present in the contralateral epididymis. Conclusions ,Although adequate antimicrobial treatment eradicated the pathogen and reduced the grade of epididymal damage, inflammation was not avoided. Subclinical inflammation of the contralateral epididymis may contribute to impaired fertility. These results indicate that an inflammatory reaction initiated by bacteria might persist as a nonbacterial process despite early therapy, or by bacteria undetectable by conventional culture techniques, and may compromise male fertility. [source] External beam radiation treatment for rectal cancer is associated with a decrease in subsequent prostate cancer diagnosisCANCER, Issue 4 2008Karen E. Hoffman MD, MHSc Abstract BACKGROUND. External beam radiation therapy (EBRT) for rectal cancer unavoidably delivers significant radiation dose to the prostate gland. The effect of this incidental exposure on subsequent prostate cancer diagnosis was investigated using the Surveillance, Epidemiology, and End Results (SEER) cancer registry. METHODS. Men diagnosed with localized or regional (L/R) rectal cancer from 1988,1997 and treated with EBRT and sphincter-sparing surgery (SSS) were identified. Men treated for L/R rectal cancer with SSS who did not receive EBRT, and men with L/R colon cancer who did not receive EBRT, were studied for comparison. Multiple Primary Standardized Incidence Ratios of observed to expected (O/E) cases of prostate cancer were calculated using SEER*Stat. RESULTS. In all, 1574 men with L/R rectal cancer treated with EBRT and SSS were identified. The median age at diagnosis was 64 and median survival was 76 months. Twenty were subsequently diagnosed with prostate cancer, a number significantly less than expected compared with the general population of similar age and race. The ratio of O/E cases was 0.28 (95% confidence interval [CI], 0.17, 0.43). In contrast, 3114 men diagnosed with rectal cancer undergoing SSS who were not treated with EBRT and 24,578 men diagnosed with colon cancer who were not treated with EBRT were subsequently diagnosed with prostate cancer at rates similar to the general population (O/E of 0.94 and 1.09). CONCLUSIONS. EBRT for L/R rectal cancer was associated with a 72% decrease in the frequency of subsequent prostate cancer diagnosis when compared with men of similar age and race. Possible mechanisms that may explain this observation are discussed. Cancer 2008. © 2007 American Cancer Society. [source] Vitamin D and calcium deficits predispose for multiple chronic diseasesEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 5 2005M. Peterlik Abstract There is evidence from both observational studies and clinical trials that calcium malnutrition and hypovitaminosis D are predisposing conditions for various common chronic diseases. In addition to skeletal disorders, calcium and vitamin D deficits increase the risk of malignancies, particularly of colon, breast and prostate gland, of chronic inflammatory and autoimmune diseases (e.g. insulin-dependent diabetes mellitus, inflammatory bowel disease, multiple sclerosis), as well as of metabolic disorders (metabolic syndrome, hypertension). The aim of the present review was to provide improved understanding of the molecular and cellular processes by which deficits in calcium and vitamin D cause specific changes in cell and organ functions and thereby increase the risk for chronic diseases of different aetiology. 1,25-dihydroxyvitamin D3 and extracellular Ca++ are both key regulators of proliferation, differentiation and function at the cellular level. However, the efficiency of vitamin D receptor-mediated intracellular signalling is limited by the negative effects of hypovitaminosis D on extrarenal 25-hydroxyvitamin D-1,-hydroxylase activity and thus on the production of 1,25-dihydroxyvitamin D3. Calcium malnutrition eventually causes a decrease in calcium concentration in extracellular fluid compartments, resulting in organ-specific modulation of calcium-sensing receptor activity. Hence, attenuation of signal transduction from the ligand-activated vitamin D receptor and calcium-sensing receptor seems to be the prime mechanism by which calcium and vitamin D insufficiencies cause perturbation of cellular functions in bone, kidney, intestine, mammary and prostate glands, endocrine pancreas, vascular endothelium, and, importantly, in the immune system. The wide range of diseases associated with deficits in calcium and vitamin D in combination with the high prevalence of these conditions represents a special challenge for preventive medicine. [source] Holmium laser enucleation for large (greater than 100 mL) prostate glandsINTERNATIONAL JOURNAL OF UROLOGY, Issue 5 2002Janaka A Hettiarachchi Abstract Background: To evaluate the holmium laser enucleation of the prostate (HoLEP) using the transurethral soft tissue morcellator (TUSTM), as a primary surgical treatment for symptomatic benign prostatic hyperplasia (BPH) with prostate glands >,100 mL. Methods: Eighteen patients with preoperative prostate volumes >,100 mL underwent the HoLEP procedure. The criteria for surgery were determined by a preoperative International Prostate Symptom Score (IPSS), a prior failure of medical therapy, and urinary retention. Results: The mean preoperative IPSS and prostate gland size were 13.8 and 142.3 mL, respectively. The total energy used by the laser was 288.4 kJ. The mean catheter time was 23.8 h and, perioperatively, no patients had electrolyte abnormalities or required blood transfusions. The 3-week postoperative IPSS was 2.8, with minimum long-term complications. Conclusions: Holmium laser enucleation of the prostate with TUSTM is a safe and effective alternative to open prostatic surgery for glands >,100 mL. [source] Comparison of the Effect of the Aromatase Inhibitor, Anastrazole, to the Antioestrogen, Tamoxifen Citrate, on Canine Prostate and SemenREPRODUCTION IN DOMESTIC ANIMALS, Issue 2009G Gonzalez Contents This study compared the efficiency of the aromatase inhibitor, anastrazole, with the antioestrogenic receptor blocker, tamoxifen, on normal (NRL) and hyperplastic prostate glands. Forty healthy dogs were classified as NRL (n = 18) or abnormal (ABN) with benign prostate hyperplasia (n = 22). The dogs were randomly assigned to one of the following six groups, treated for 60 days; oral placebo for normal (NRL-PLC; n = 6) and abnormal (ABN-PLC; n = 6), oral anastrazole 0.25,1 mg/day, for normal (NRL-ANZ, n = 6) and abnormal (ABN-ANZ, n = 8) and oral tamoxifen citrate 2.5,10 mg/day for normal (NRL-TMX; n = 6) and abnormal (ABN-TMX; n = 8) dogs. The dogs were evaluated before treatment and then monthly for 4 months. At the end of the treatment, the prostatic volume decreased by 28.5 ± 4.3%, 21.6 ± 6.3% and 0.7 ± 1.0% in the ABN-TMX, ABN-ANZ and ABN-PLC (p < 0.01), respectively. From then on, prostatic volume began to increase without reaching pre-treatment values at the end of the study. In the ABN animals, there were no differences for this parameter between ANZ and TMX treatment (p > 0.1), whereas in the NRL animals ANZ produced a less pronounced decrease (p < 0.05), libido, testicular consistency and scrotal diameter decreased during treatment in the TMX group (p > 0.05). These parameters and sperm volume, count, motility and morphological abnormalities remained unaltered throughout the study in the ANZ and PLC groups (p > 0.05). There were no haematological nor biochemical side effects. Anastrazole might offer a safe and effective alternative for the medical management of dogs with benign prostatic hyperplasia. [source] The developmental expression profile of PAX2 in the murine prostateTHE PROSTATE, Issue 6 2010Qian Chen Abstract BACKGROUND Nine transcription factors comprise the PAX gene family that regulate organogenesis. The urogenital system of PAX2 null male mice fails to develop properly. PAX2 is overexpressed in PC3 cells. Therefore, PAX2 is implicated in both prostate organogenesis and cancer. However, the expression pattern/profile of PAX2 in the prostate is unknown. METHODS PAX2/5/8 expression was surveyed in E16.5 male urogenital sinus (UGS) by RT-PCR. Prostate samples from 10 developmental stages in C3H male mice were used in quantitative reverse-transcript PCR (Q-PCR) and Western blotting (WB). RT-PCR and WB measured PAX2 expression in prostatic lobes or UGS layers, to identify local-regional expression patterns. Cytoplasmic versus nuclear expression was examined by WB. A castration series in adult C3H male mice and R1881 treatment in serum-free LNCaP cells examined androgen control of PAX2. RESULTS PAX2 mRNA levels are higher in early developmental stages as compared to postpubertal prostates. RT-PCR and/or WB indicated a dorsal epithelial,nuclear localization of PAX2. PAX2 mRNA and protein increase postcastration. R1881 decreases expression of PAX2 mRNA in LNCaP cells as compared to controls. CONCLUSIONS The expression profile of PAX2 indicates that it may regulate early, androgen-independent stages of murine prostate development, particularly for dorsally derived prostate glands. PAX2 expression appears to be associated with a dorsally localized epithelial cell population that is castration insensitive and retains proliferative and differentiative potential. Such a population of cells may represent a subset of stem-like cells having some characteristics in common with castrate-resistant prostate cancer cells. Prostate 70: 654,665, 2010. © 2009 Wiley-Liss, Inc. [source] Monocyte chemotactic protein-1 (MCP-1/CCL2) is associated with prostatic growth dysregulation and benign prostatic hyperplasiaTHE PROSTATE, Issue 5 2010Kazutoshi Fujita Abstract BACKGROUND Chronic inflammation is commonly observed in benign prostate hyperplasia (BPH), and prostate tissue often contains increased inflammatory infiltrates, including T cells and macrophages. Cytokines are not only key mediators of inflammation but may also play important roles in the initiation and progression of BPH. METHODS In order to determine what cytokines might be involved in prostatic enlargement, expressed prostatic secretions (EPS) from ex vivo prostates were analyzed by human cytokine antibody microarray and ELISA. Prostate epithelial cells (PrEC) and prostate stromal cells (PrSC) were used for ELISA, proliferation, and Western blot assays. RESULTS Monocyte chemotactic protein-1 (MCP-1/CCL2) was one of the most elevated proteins in secretions from large prostate glands. PrSC were found to secrete MCP-1; Western blotting showed that both PrSC and PrEC express the MCP-1 receptor CCR2 which by RT-PCR was the CCR2b isoform. Proliferation assays showed that MCP-1 stimulates the proliferation of PrEC, but not PrSC, and that a specific MCP-1 antagonist (RS102895) suppressed this effect. Conditioned medium from PrSC stimulated the proliferation of PrEC as well, an effect completely inhibited by both RS102895 and a neutralizing anti-MCP-1 monoclonal antibody. The inflammatory cytokines interleukin (IL)-1,, interferon-,, and IL-2 enhanced the secretion of MCP-1 from PrEC and PrSC. In addition, MCP-1 levels in EPS correlated with mRNA levels of the macrophage marker CD68 in the same secretions. CONCLUSIONS The cytokine MCP-1, of apparent prostatic stromal cell origin, may play an important role in prostatic enlargement and BPH, and is a candidate biomarker for these pathologic processes. Prostate 70: 473,481, 2010. © 2009 Wiley-Liss, Inc. [source] Immunohistochemical analysis of NF-,B signaling proteins IKK,, p50/p105, p52/p100 and RelA in prostate cancersAPMIS, Issue 8 2009SEONG IL SEO Seo SI, Song SY, Kang MR, Kim MS, Oh JE, Kim YR, Lee JY, Yoo NJ, Lee SH. Immunohistochemical analysis of NF-,B signaling proteins IKK,, p50/p105, p52/p100 and RelA in prostate cancers. APMIS 2009; 117:623,8. Activation of nuclear factor-kappa B (NF-,B) signaling is considered an important mechanism in the development of prostate cancers. A recent study revealed that I,B kinase epsilon (IKK,), an activator of NF-,B, was overexpressed in breast cancers and acted as an oncogene. Expression of NF-,B members has been reported in prostate cancer tissues, but expression of IKK, has not yet been studied in prostate cancers. In this study, we attempted to explore as to whether expressions of IKK, and NF-,B members p50/105, p52/p100 and RelA are altered in prostate cancers. We analyzed the expression of IKK,, p50/105, p52/p100 and RelA in 107 prostate adenocarcinoma tissues by immunohistochemistry using a tissue microarray (TMA) method. In the TMA, IKK, is expressed in basal cells, but not in alveolar cells in normal prostate glands. IKK, is expressed in 60.0% of prostate intraepithelial neoplasm (PIN) and 70.1% of the prostate cancers in the cytoplasm. Nuclear immunostainings of NF-,B members p50/105, p52/p100 and RelA, which are considered activation of NF-,B signaling, were observed respectively in 28.0%, 18.7% and 37.4% of the cancers. Nuclear staining was detected neither in normal alveolar cells nor in PIN. However, none of the expression of p50/105 nor p52/p100 nor RelA nor IKK, was associated with pathologic characteristics, including size of the cancers, age, Gleason score and stage. The increased cytoplasmic expression of IKK, as well as the increased nuclear expressions of p50/105, p52/p100 and RelA in the prostate cancers compared to normal alveolar cells suggested that overexpression of these proteins may be related to activation of the NF-,B pathway and might play a role in tumorigenesis of prostate cancers. [source] | |||||||||||||||||||||||||||||||