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Prostate Tissue (prostate + tissue)
Kinds of Prostate Tissue Terms modified by Prostate Tissue Selected AbstractsAlpha-methylacyl-CoA racemase: a multi-institutional study of a new prostate cancer markerHISTOPATHOLOGY, Issue 3 2004Z Jiang Aim :,To test whether ,-methylacyl-CoA racemase (AMACR) is a sensitive and specific marker of prostate cancer. Methods and results :,The expression levels of AMACR mRNA were measured by real-time polymerase chain reaction. A total of 807 prostatic specimens were further examined by immunohistochemistry specific for AMACR. Quantitative immunostaining analyses were carried out by using the ChromaVision Automated Cellular Imaging System and the Ariol SL-50 Imaging System, respectively. AMACR mRNA levels measured in prostatic adenocarcinoma were 55 times higher than those in benign prostate tissue. Of 454 cases of prostatic adenocarcinoma, 441 were positive for AMACR, while 254 of 277 cases of benign prostate were negative for AMACR. The sensitivity and specificity of AMACR immunodetection of prostatic adenocarcinomas were 97% and 92%, respectively. Both positive and negative predictive values were 95%. By automatic imaging analyses, the AMACR immunostaining intensity and percentage in prostatic adenocarcinomas were also significantly higher than those in benign prostatic tissue (105.9 versus 16.1 for intensity, 45.7% versus 0.02% and 35.03% versus 4.64% for percentage, respectively). Conclusions :,We have demonstrated the promising features of AMACR as a biomarker for prostate cancer in this large series and the potential to develop automated quantitative diagnostic tests. [source] Effects of steroids on oxytocin secretion by the human prostate in vitroINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 1 2004S. J. Assinder Summary Oxytocin (OT) concentrations are elevated in prostate tissue of patients with benign prostatic hyperplasia (BPH). Oxytocin specifically increases growth, 5 , -reductase activity and contractility in the prostate. In the rat prostatic OT concentrations are regulated by gonadal steroids, with androgens reducing but oestrogens increasing OT concentrations. The regulation of prostatic oxytocin in man is not understood. This study investigates the effects of gonadal steroids on oxytocin production by the human prostate. Primary explants (approx. 1 mm3) of prostate tissue from patients with BPH were incubated in Dulbecco's modified Eagle's media in the absence or presence of 10 nmol/L testosterone (T), 10 nmol/L dihydrotestosterone (DHT), T or DHT plus 100 nmol/L of the anti-androgen cyproterone acetate (CPA), 55 pmol/L diethylstilbestrol (DES), or DES plus DHT. The amount of oxytocin secreted into the media after 3 days was measured by radioimmunoassay. Testosterone and DHT significantly increased oxytocin concentrations secreted into the media from 0.86 ± 0.11 ng/g of tissue (control) to 1.51 ± 0.14 ng/g (p < 0.01) and 1.54 ± 0.13 ng/g (p < 0.05), respectively. Incubation of tissue samples with CPA resulted in oxytocin concentrations similar to control levels. Treatment with DES caused a significant increase from 1.99 ± 0.71 to 3.98 ± 1.36 ng/g (p < 0.05). A similar increase was measured in media of tissue incubated in DES plus DHT (p < 0.001). The results demonstrate that, unlike the rat where androgens decrease oxytocin, in hyperplastic human prostate tissue both androgens and oestrogens increase oxytocin. This imbalance in the regulation of oxytocin may result in promoting prostatic overgrowth in the pathogenesis of BPH. [source] The CAG repeat polymorphism within the androgen receptor gene and maleness,INTERNATIONAL JOURNAL OF ANDROLOGY, Issue 2 2003Michael Zitzmann Summary The androgen testosterone and its metabolite dihydrotestosterone exert their effects on gene expression and thus effect maleness via the androgen receptor (AR). A diverse range of clinical conditions starting with complete androgen insensitivity has been correlated with mutations in the AR. Subtle modulations of the transcriptional activity induced by the AR have also been observed and frequently assigned to a polyglutamine stretch of variable length within the N-terminal domain of the receptor. This stretch is encoded by a variable number of CAG triplets in exon 1 of the AR gene located on the X chromosome. First observations of pathologically elongated AR CAG repeats in patients with X-linked spino-bulbar muscular atrophy showing marked hypoandrogenic traits were supplemented by partially conflicting findings of statistical significance also within the normal range of CAG repeat length: an involvement of prostate tissue, spermatogenesis, bone density, hair growth, cardiovascular risk factors and psychological factors has been demonstrated. The highly polymorphic nature of glutamine residues within the AR protein implies a subtle gradation of androgenicity among individuals within an environment of normal testosterone levels providing relevant ligand binding to ARs. This modulation of androgen effects may be small but continuously present during a man's lifetime and, hence, exerts effects that are measurable in many tissues as various degrees of androgenicity and represents a relevant effector of maleness. It remains to be elucidated whether these insights are important enough to become part of individually useful laboratory assessments. [source] Expression of microRNA-221 is progressively reduced in aggressive prostate cancer and metastasis and predicts clinical recurrenceINTERNATIONAL JOURNAL OF CANCER, Issue 2 2010Martin Spahn Abstract Emerging evidence shows that microRNAs (miR) are involved in the pathogenesis of a variety of cancers, including prostate carcinoma (PCa). Little information is available regarding miR expression levels in lymph node metastasis of prostate cancer or the potential of miRs as prognostic markers in this disease. Therefore, we analyzed the global expression of miRs in benign, hyperplastic prostate tissue (BPH), primary PCa of a high risk group of PCa patients, and corresponding metastatic tissues by microarray analysis. Consistent with the proposal that some miRs are oncomirs, we found aberrant expression of several miRs, including the downregulation of miR-221, in PCa metastasis. Downregulation of miR-221 was negatively correlated with the expression of the proto-oncogen c-kit in primary carcinoma. In a large study cohort, the prostate-specific oncomir miR-221 was progressively downregulated in aggressive forms of PCa. Downregulation of miR-221 was associated with clinicopathological parameters, including the Gleason score and the clinical recurrence during follow up. Kaplan,Meier estimates and Cox proportional hazard models showed that miR-221 downregulation was linked to tumor progression and recurrence in a high risk prostate cancer cohort. Our results showed that progressive miR-221 downregulation hallmarks metastasis and presents a novel prognostic marker in high risk PCa. This suggests that miR-221 has potential as a diagnostic marker and therapeutic target in PCa. [source] Association of kallikrein expression in nipple aspirate fluid with breast cancer riskINTERNATIONAL JOURNAL OF CANCER, Issue 4 2004Edward R. Sauter Abstract Human kallikreins (hK) 2, 3, 6 and 10 are expressed in breast and prostate tissue. hK2 and hK3 (prostate-specific antigen, PSA) are used to screen for prostate cancer. hK6 and hK10 are downregulated in breast cancer compared to normal breast tissue. We demonstrated that levels of PSA in nipple aspirate fluid (NAF) are lower in women with breast cancer than in normal women. We hypothesize that the expression of hK2, 3, 6 and 10 are related and important in detecting breast cancer. The goals of this study are to determine the level of expression of kallikreins in NAF and serum, the association of hK2, 3, 6 and 10 in NAF, and the association of each of the kallikreins with breast cancer. In NAF from 275 women, hK3, 6 and 10 were detectable in , 90% and hK2 in 74% of samples analyzed. NAF levels were highest for hK6 and lowest for hK2, regardless of cancer and menopausal status. hK3 was detectable in 15/29 (52%) and hK2 in 0/29 serum samples collected from 6 women. hK2 and hK3 were concentrated in NAF vs. matched serum. The 4 kallikreins were associated with the exception of hK2 with hK6 or hK10. PSA levels were higher in normal pre- than postmenopausal subjects (but not women with breast cancer), whereas levels of hK2, 6 and 10 did not differ by menopausal status. hK2 and PSA were associated with both pre- and postmenopausal breast cancer; hK6 and 10 were not. hK2 and PSA were more associated with pre- than postmenopausal breast cancer. Using logistic regression, PSA and menopausal status provided the best model of breast cancer prediction, with a sensitivity of 91% and specificity of 39%. In conclusion, 4 kallikreins are expressed in NAF. hK2 and PSA, and hK6 and hK10 are highly associated. Higher premenopausal PSA levels suggest the influence of ovarian steroids. PSA shows the most promise in aiding in the early detection of breast cancer. © 2003 Wiley-Liss, Inc. [source] Comparison of microvessel densities in rat prostate tissues treated with finasteride, bicalutamide and surgical castration: A preliminary studyINTERNATIONAL JOURNAL OF UROLOGY, Issue 2 2005CEVDET KAYA Abstract Background: A group of anti-androgens with different mechanisms of action and adverse effects have been investigated in patients with gross hematuria related to benign prostate hyperplasia; however, there is not yet any consensus about the standard management of these patients. The present study aims to identify if any one type of the hormonal intervention is superior in terms of the suppression of microvessel formation in the prostate. Materials and methods: A total of 28 mature, healthy male Sprague,Dawley rats (300 ± 50 g) were used in this study. The rats were randomly assigned to one of four groups (n = 7 per group). The effects of three different hormonal therapies on angiogenesis and microvascularity in rat ventral prostate were compared. Groups 1 and 2 were treated for 28 days with finasteride and bicalutamide, respectively, and rats from Group 3 underwent surgical castration. Following treatment, all rats included in the study underwent dissection of the ventral prostate and immunohistochemical analysis of microvessel density by factor VIII-related antigen. Results: The mean number of microvessels in the finasteride and bicalutamide groups was 24.5 (±8.44 SE) and 27 (±9.89 SE) respectively. In contrast, the castration and control groups had microvessel numbers of 12.9 (±5.35 SE) and 40.3 (±5.03 SE) respectively. Differences were statistically significant between all three treatment groups and the controls (P < 0.005); the number of microvessels in rat prostate tissues of the control group was significantly higher than the treatment groups. Mean microvessel densities in the bicalutamide and finasteride groups were significantly higher than microvessel densities in the castration group (P < 0.005). There was no statistically significant difference between mean microvessel number in rat prostate tissue treated with finasteride or bicalutamide (P > 0.05). Conclusions: Even though finasteride was not as effective as castration in reducing microvessel number, its effect was equal to that of bicalutamide in terms of suppressing the angiogenesis in prostatic tissue. Based on the findings of the present study, finasteride might offer a viable option in the management of macroscopic hematuria by inhibition of microvessel formation within the prostatic tissue. Further clinical studies are warranted. [source] Biochemical and ultrastructural alterations in the rat ventral prostate due to repetitive alcohol drinkingJOURNAL OF APPLIED TOXICOLOGY, Issue 4 2007M. I. Díaz Gómez Abstract Previous studies showed that cytosolic and microsomal fractions from rat ventral prostate are able to biotransform ethanol to acetaldehyde and 1-hydroxyethyl radicals via xanthine oxidase and a non P450 dependent pathway respectively. Sprague Dawley male rats were fed with a Lieber and De Carli diet containing ethanol for 28 days and compared against adequately pair-fed controls. Prostate microsomal fractions were found to exhibit CYP2E1-mediated hydroxylase activity significantly lower than in the liver and it was induced by repetitive ethanol drinking. Ethanol drinking led to an increased susceptibility of prostatic lipids to oxidation, as detected by t-butylhydroperoxide-promoted chemiluminiscence emission and increased levels of lipid hydroperoxides (xylenol orange method). Ultrastructural alterations in the epithelial cells were observed. They consisted of marked condensation of chromatin around the perinuclear membrane, moderate dilatation of the endoplasmic reticulum and an increased number of epithelial cells undergoing apoptosis. The prostatic alcohol dehydrogenase activity of the stock rats was 4.84 times lower than that in the liver and aldehyde dehydrogenase activity in their microsomal, cytosolic and mitochondrial fractions was either not detectable or significantly less intense than in the liver. A single dose of ethanol led to significant acetaldehyde accumulation in the prostate. The results suggest that acetaldehyde accumulation in prostate tissue might result from both acetaldehyde produced in situ but also because of its low aldehyde dehydrogenase activity and its poor ability to metabolize acetaldehyde arriving via the blood. Acetaldehyde, 1-hydroxyethyl radical and the oxidative stress produced may lead to epithelial cell injury. Copyright © 2007 John Wiley & Sons, Ltd. [source] Prostate inflammation and its potential impact on prostate cancer: A current reviewJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 5 2008Jessica Haverkamp Abstract Recent studies have identified a role for inflammation in the development and progression of several cancers, such as liver, stomach and the large intestine. Data from several studies has shown correlations between soluble inflammatory mediators, such as cytokines, chemokines and growth factors. However, a direct relationship between inflammation and prostate cancer has yet to be identified. Two major hurdles currently exist which limit the study of this relationship are first that animal models available for studying prostate inflammation are lmited, and secondly that relatively little is known about the inflammatory response in the prostate. Here we first review the data demonstrating a correlation between inflammation and prostate cancer as well as review what is currently known about the inflammatory response in the prostate and the impact this inflammation has on the prostate tissue. J. Cell. Biochem. 103: 1344,1353, 2008. © 2007 Wiley-Liss, Inc. [source] Molecular regulation of androgen action in prostate cancer,JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2006Scott M. Dehm Abstract Androgens are critical regulators of prostate differentiation and function, as well as prostate cancer growth and survival. Therefore, androgen ablation is the preferred systemic treatment for disseminated prostate cancer. Androgen action is exerted in target tissues via binding the androgen receptor (AR), a nuclear receptor transcription factor. Historically, the gene expression program mediated by the AR has been poorly understood. However, recent gene expression profiling and more traditional single-gene characterization studies have revealed many androgen-regulated genes that are important mediators of androgen action in both normal and malignant prostate tissue. This review will focus on the androgen-regulated gene expression program, and examine how recently identified androgen-regulated genes are likely to contribute to the development and progression of prostate cancer. We will also summarize several recent studies that have attempted to unravel how these genes are deregulated in androgen depletion independent prostate cancer. J. Cell. Biochem. 99: 333,344, 2006. © 2006 Wiley-Liss, Inc. [source] RUNX1 (AML-1) and RUNX2 (AML-3) cooperate with prostate-derived Ets factor to activate transcription from the PSA upstream regulatory regionJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2006Marcie Fowler Abstract The RUNX transcription factors (RUNX1, RUNX2, and RUNX3) play essential roles in hematopoiesis and skeletal development. Consistent with these roles in differentiation and cell cycle, the activity of both RUNX1 and RUNX3 is perturbed in cancer. To determine a role for the RUNX factors in prostate biology, we investigated the expression of RUNX factors in prostate epithelial cell lines and normal prostate tissue. RUNX1, RUNX2, and RUNX3 were expressed in both normal prostate tissue and an immortalized, non-transformed cell line. We found that prostate cancer-derived cell lines expressed RUNX1 and RUNX2, but not RUNX3. Next, we sought to identify prostate-specific genes whose expression could be regulated by RUNX proteins. Four consensus RUNX sites are located within the prostate-specific antigen (PSA) regulatory region. Chromatin immunoprecipitation (ChIP) analysis showed that RUNX1 is specifically bound to the PSA regulatory region in LNCaP cells. RUNX1 and RUNX2 activated the PSA regulatory region alone or cooperatively with prostate- derived ETS factor (PDEF) and RUNX1 physically associated with PDEF. Taken together, our results suggest that RUNX factors participate in prostate epithelial cell function and cooperate with an Ets transcription factor to regulate PSA gene expression. J. Cell. Biochem. © 2005 Wiley-Liss, Inc. [source] Expression of RIZ1 protein (Retinoblastoma-interacting zinc-finger protein 1) in prostate cancer epithelial cells changes with cancer grade progression and is modulated in vitro by DHT and E2JOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2009Valentina Rossi The nuclear protein methyl-transferase Retinoblastoma-interacting zinc-finger protein 1 (RIZ1) is considered to be a downstream effector of estrogen action in target tissues. Silencing of RIZ1 expression is common in many tumors. We analyzed RIZ1 expression in normal and malignant prostate tissue and evaluated whether estradiol (E2) or dihydrotestosterone (DHT) treatment modulated RIZ1 in cultured prostate epithelial cells (PEC). Moreover, we studied the possible involvement of RIZ1 in estrogen action on the EPN prostate cell line, constitutively expressing both estrogen receptor (ER)-, and ,. RIZ1 protein, found in the nucleus of normal PECs by immunohistochemistry, was progressively lost in cancer tissues as the Gleason score increased and was only detected in the cytoplasmic compartment. RIZ1 transcript levels, as assayed by semi-quantitative RT-PCR in primary PEC cultures, were significantly reduced in cancer cells (P,<,0.05). In EPN DHT treatment significantly increased RIZ1 transcript and protein levels (P,<,0.05); E2 induced a reduction of S phase without significant changes of RIZ1 expression. In E2-treated EPN cell extracts RIZ co-immunoprecipitated with ER, and ER,. Our data demonstrate that RIZ1 is expressed in normal PECs and down-regulated in cancer cells, with a switch of its sub-cellular localization from the nucleus to the cytoplasm upon cancer grade progression. RIZ1 expression levels in the PECs were modulated by DHT or E2 treatment in vitro. Furthermore, the E2 effects on ER-expressing prostate cells involve RIZ1, which confirms a possible role for ER-mediated pathways in a non-classic E2 -target tissue. J. Cell. Physiol. 221: 771,777, 2009. © 2009 Wiley-Liss, Inc. [source] High-resolution magic angle spinning proton NMR analysis of human prostate tissue with slow spinning ratesMAGNETIC RESONANCE IN MEDICINE, Issue 3 2003Jennifer L. Taylor Abstract The development of high-resolution magic angle spinning (HR-MAS) NMR spectroscopy for intact tissue analysis and the correlations between the measured tissue metabolites and disease pathologies have inspired investigations of slow-spinning methodologies to maximize the protection of tissue pathology structures from HR-MAS centrifuging damage. Spinning sidebands produced by slow-rate spinning must be suppressed to prevent their complicating the spectral region of metabolites. Twenty-two human prostatectomy samples were analyzed on a 14.1T spectrometer, with HR-MAS spinning rates of 600 Hz, 700 Hz, and 3.0 kHz, a repetition time of 5 sec, and employing various rotor-synchronized suppression methods, including DANTE, WATERGATE, TOSS, and PASS pulse sequences. Among them, DANTE, as the simplest scheme, has shown the most potential in suppression of tissue water signals and spinning sidebands, as well as in quantifying metabolic concentrations. Magn Reson Med 50:627,632, 2003. © 2003 Wiley-Liss, Inc. [source] Molecular characterization of the G,-globin-Tag transgenic mouse model of hormone refractory prostate cancer: Comparison to human prostate cancer,THE PROSTATE, Issue 6 2010Alfonso Calvo Abstract BACKGROUND Prostate cancer (PrCa) has a high incidence in Western countries and at present, there is no cure for hormone refractory prostate cancer. Transgenic mouse models have proven useful for understanding mechanisms of prostate carcinogenesis. The characterization of genetically modified mouse PrCa models using high-throughput genomic analyses provides important information to guide appropriate experiment applications for such model. METHODS We have analyzed the transcriptome of the hormone refractory and highly metastatic Fetal Globin-SV40/T-antigen (G,-globin-Tag) transgenic mouse model for PrCa compared to normal mouse prostate tissue. Gene expression patterns found in G,-globin-Tag mouse prostate tumors were compared with publicly available human localized and metastatic prostate tumors (GEO accession # GSE3325) through hierarchical cluster analysis, Pearson's rank correlation coefficient, and Self Organizing Feature Maps (SOM) analyses. RESULTS G,-globin-Tag tumors clustered closely with human metastatic tumors and gene expression patterns had a significant correlation (P,<,0.01), unlike human localized primary tumors (P,>,0.6). Bioinformatic analyses identified deregulated genetic pathways and networks in G,-globin-Tag tumors, which displayed similarities to alterations in human PrCa. Changes in the expression of genes involved in DNA replication and repair (Rb1, p53, Myc, PCNA, DNMT3A) and growth factor signaling pathways (TGF,2, ERK1/2, NRas, and Notch1) are deregulated in the G,-globin-Tag tumors, suggesting their key role in the oncogenic process. Identification of an enrichment of putative binding sites for transcription factors revealed eight transcription factors that may be important in G,-globin-Tag carcinogenesis, including SP1, NF-Y, CREB, Elk1, and E2F. Novel genes related to microtubule regulation were also identified in G,-globin-Tag tumors as potentially important candidate targets for PrCa. Overexpression of stathmin-1, whose expression was increased in human metastatic prostate tumors, was validated in G,-globin-Tag tumors by immunohistochemistry. This protein belongs to the SV40/T-antigen cancer signature identified in previous studies in prostate, breast, and lung cancer mouse models. CONCLUSIONS Our results show that the G,-globin-Tag model for hormone refractory PrCa shares important features with aggressive, metastatic human PrCa. Given the role of stathmin-1 in the destabilization of microtubles and taxane resistance, the G,-globin-Tag model and other SV40/T-antigen driven transgenic models may be useful for testing potential therapies directed at stathmin-1 in human prostate tumors. Prostate 70: 630,645, 2010. Published 2010 Wiley-Liss, Inc. [source] POU5F1P1, a putative cancer susceptibility gene, is overexpressed in prostatic carcinomaTHE PROSTATE, Issue 6 2010Silvia Kastler Abstract BACKGROUND Association between genetic variants located on human chromosome 8q24.21 with an increased risk for prostatic carcinoma has been well established. POU5F1P1, a processed pseudogene homologous to the pluripotency factor OCT4, is the only sequence with coding capacity in this region. The objective of this study was to investigate the POU5F1P1 expression in prostatic carcinoma and carcinoma surrounding prostatic tissue. METHODS RT-PCR and real-time PCR was used to measure the expression of POU5F1P1 relative to the expression of HPRT1 in cell lines, prostatic carcinoma and carcinoma surrounding prostatic tissue. The structure of the POU5F1P1 mRNA and the promoter sequence were elucidated by 5,-RACE experiments. The POU5F1P1 protein was shown with immunohistochemistry on prostate tissue. RESULTS POU5F1P1 was found to be the only member of the POU5F1 family to be expressed in prostate with over-expression in prostatic carcinoma compared to surrounding prostatic tissue probably because of an increased density of expressing cells. The POU5F1P1 expression is driven by a variety of promoter structures scattered over a genomic region of 860 kB. CONCLUSIONS The over-expression of POU5F1P1 in prostatic carcinoma in addition to its genomic location and the putative function of its gene product render POU5F1P1 a good candidate to harbour functional genetic variants which modulate prostatic cancer susceptibility. Prostate 70: 666,674, 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] Inflammatory processes of prostate tissue microenvironment drive rat prostate carcinogenesis: Preventive effects of celecoxibTHE PROSTATE, Issue 2 2009Narayanan K. Narayanan Abstract BACKGROUND Prostate tissue microenvironment is susceptible to several risk factors including carcinogens, dietary factors, hormones, cytokines and growth factors that could induce chronic inflammation. Because of the difference in the serum levels and the intrinsic ability of monocytes/macrophages to cause harm, the transcriptional responses triggered by inflammatory stimuli must be controlled. Unfortunately, an in-depth association between prostate cancer and potential mediators of inflammation has not been completely investigated. METHODS To determine whether activated macrophage (infiltrating monocytes), iNOS and NF-,B are primary mediators of inflammation, besides COX-2, in prostate carcinogenesis, we examined tissue sections of rat prostate tumor induced by N -methyl- N -nitrosourea (MNU) plus testosterone in a follow-up study. We performed H&E and immunohsitochemical staining of the prostate tissue to detect specific markers of inflammation. RESULTS We report an increase in infiltrating monocyte, iNOS, NF-,Bp65, VEGF and TNF-, at the early and advanced stages of tumor growth in MNU plus testosterone treated rats. Monocyte infiltration was often found in the stromal and perivascular regions of the DL prostate. We conclude for the first time that prostate cancer induced by MNU plus testosterone partly involves mediators of inflammation which could trigger the process of carcinogenesis and cause loss of apoptosis. Selective COX-2 inhibitor celecoxib at a dose of 500 mg/kg/bw administered for 52 weeks reduced infiltrating monocytes, inhibited iNOS, NF-,B p65 expression, induced apoptosis and tumor growth inhibition. CONCLUSION Carcinogen plus testosterone induced prostate carcinogenesis showing activation of macrophage, iNOS and NF-,Bp65 could be prevented by celecoxib or related anti-inflammatory agents. Prostate 69: 133,141, 2009. © 2008 Wiley,Liss, Inc. [source] Insulin-like growth factor binding protein-3 (IGFBP-3) in the prostate and in prostate cancer: Local production, distribution and secretion pattern indicate a role in stromal-epithelial interactionTHE PROSTATE, Issue 11 2008Petra Massoner Abstract Background Insulin-like growth factor binding protein 3 (IGFBP-3) exerts inhibitory and proapoptotic effects on prostate cancer cells. Serum levels of IGFBP-3 were found to be associated with the risk of prostate cancer, but the data are still inconclusive. We present a detailed analysis of the expression and localization of IGFBP-3 in the prostate and a comparison with its expression pattern in tumors. Methods Expression and localization of IGFBP-3 were analyzed in cellular models and tissue by real-time RT-PCR, ELISA, immunohistochemistry, and immunofluorescence. Results All cell types of a panel of benign epithelial, stromal and tumor prostate cells expressed IGFBP-3. Significantly higher expression levels were registered in stromal cells. TGF-, stimulation boosted IGFBP-3 levels 60-fold in stromal cells. The pattern of expression was confirmed in microdissected tissue samples. Protein levels measured by ELISA paralleled the mRNA levels and more than 80% of IGFBP-3 was secreted. On tissue immunostaining, IGFBP-3 was found to be mainly located in the epithelium. The pattern suggested secretion of IGFBP-3, which was confirmed in prostate tissue cultured ex vivo and the ejaculate of vasectomized men. IGFBP-3 levels were increased in primary tumors but did not differ from benign epithelium in metastases and local recurrent tumors. Conclusions We registered a significant local production of IGFBP-3 in the prostate, which may well override the effect of protein entering from blood. The stroma,particularly reactivated stroma,is the main source of IGFBP-3 in the prostate, suggesting that this peptide acts as a mediator of stromal-epithelial interactions. Prostate 68: 1165,1178, 2008. © 2008 Wiley-Liss, Inc. [source] Histopathological and immunohistochemical characterization of canine prostate cancerTHE PROSTATE, Issue 5 2008Chen-Li Lai Abstract Background In this study we try to identify the origin of canine prostate cancer (cPC) by classifying the tumors histological subtypes and relate these subtypes to their combined expressional characteristics of several tissue specific and differentiation markers. Methods cPCs were examined histomorphologically and by immunohistochemical detection of the cytokeratin markers CK14, HMWCK, CK5, CK18, and CK7, and of the markers UPIII, PSA and PSMA. Results Histopathologically, six growth patterns could be differentiated. The most frequent patterns were solid, cribriform and micropapillary growth patterns, while sarcomatoid, small acinar/ductal, and tubulo-papillary growth patterns were less frequent present. Solid growth patterns were significantly (P,=,0.027) more often seen in castrated dogs. Immunohistochemically, about half of the cPC cases showed expression of PSA (8/20) and PSMA (10/20); 85% and 60% of the cPC expressed UPIII (17/20) and CK7 (12/20), while 13 and 12 cPC expressed CK5 and CK14, respectively; all cPC expressed CK18. CK14 was significantly more often and UPIII less frequent expressed in the solid growth patterns than in the micropapillary and cribriform patterns, respectively. Conclusions Canine prostate cancer appear to be more aggressive and of a less differentiated type than most common human prostate cancers. Comparing the expression patterns of the markers in cPC to those in normal canine prostate tissue, cPC most likely originates from the collecting ducts rather than from the peripheral acini. Given also the fact that canine prostate cancer is unresponsive to androgen withdrawal therapy, canine prostate cancer mostly resembles human, androgen refractory, poorly differentiated prostate cancer. Prostate 68: 477,488, 2008. © 2008 Wiley-Liss, Inc. [source] Characterization of benign and malignant prostate epithelial Hoechst 33342 side populationsTHE PROSTATE, Issue 13 2007Mick D. Brown Abstract Background The prostate epithelial stem cell has been proposed as the primary origin of neoplastic change in prostate cancer. However, the isolation and characterization of unexpanded prostate epithelial stem cells have proven problematic. Methods A prostate epithelial side population (SP) has been isolated utilizing a modified Hoechst 33342 dye efflux assay from both benign and malignant prostate tissue. CD45,ve, integrin ,2+ve Hoechst 33342 SP and NSP cells were isolated by FACS, immunophenotyped and functionally characterized in 3D culture. Results FACS analysis revealed a verapamil sensitive SP accounting for 0.93,±,0.12% and 0.57,±,0.11% of the total epithelial population from both benign and malignant prostates. The benign SP phenotype revealed a heterogeneous cell population consisting predominantly of small basal cells containing minimal cytoplasm. Conversely, the malignant SP was of undetermined acinar origin and with a complete loss of expression of the CDK2 inhibitor p21WAF1/Cip1. In vitro androgen-enhanced 3D culture of the benign and malignant SP cells led to the production of spheroids which had acinus like morphology and expressed primitive and basal cell markers. Incorporation of the CD133 marker isolated a further SP sub-fraction accounting for 0.037,±,0.01% of epithelial cells. Conclusions Our observations are consistent with the Hoechst 33342 dye efflux assay isolating a stem cell enriched population which can be further sub-fractionated by CD133 selection. Moreover, the loss of the CDK inhibitor in malignancy is consistent with the hypothesis that neoplastic change originates in the stem cell compartment. Prostate 67: 1384,1396, 2007. © 2007 Wiley-Liss, Inc. [source] Nuclear androgen receptors recur in the epithelial and stromal compartments of malignant and non-malignant human prostate tissue several months after castration therapyTHE PROSTATE, Issue 12 2007Pernilla Wikström Abstract BACKGROUND As changed paracrine support from androgen receptor (AR)-positive cells in the prostate stroma contribute to castration-induced glandular involution, we examined if the subsequent relapse to androgen-independent epithelial cell growth could be related to reactivation of AR signaling in the stroma. MATERIALS AND METHODS Human prostate tissue taken before, within 14 days, and at suspected local tumor relapse after surgical castration therapy was immunostained for AR. RESULTS Castration initially decreased nuclear AR staining in epithelial and stroma cells, in both tumor and non-malignant tissue, but after some months, it reappeared. CONCLUSIONS Local tumor relapse was associated with reappearance of nuclear AR not only in tumor epithelial cells but also in the tumor stroma. Reappearance of nuclear AR in non-malignant prostate cells may be a physiological response to long-term systemic androgen ablation that could influence tumor growth. Prostate 67: 1277,1284, 2007. © 2007 Wiley-Liss, Inc. [source] Secretagogin is a new neuroendocrine marker in the human prostateTHE PROSTATE, Issue 5 2007Katja Adolf Abstract Background Neuroendocrine (NE) differentiation in prostate cancer (PCa), promoted by NE cell secreted products, appears to be associated with tumor progression, poor prognosis, and hormone-refractory disease. We recently reported secretagogin, a hexa-EF-hand Ca2+ binding protein, as a novel NE marker in carcinoid tumors of the lung and the gastrointestinal tract. The present study analyzes the expression of secretagogin in normal and malign prostate tissue. Methods We analyzed immunoreactivity for secretagogin, chromogranin A (CgA), neuron specific enolase (NSE), and synaptophysin (SYN) in consecutive sections from 87 formalin-fixed paraffin-embedded (FFPE) benign hyperplastic (n,=,10) and prostate adenocarcinoma (n,=,77) specimens. The intracellular distribution of secretagogin, CgA, and NSE was examined by confocal fluorescent microscopy, and we characterized secretagogin in eight samples by Western blotting. Results Secretagogin is cytoplasmic and nuclear expressed in NE and NE differentiated cells, and to a lesser extent in epithelial cells, in the benign prostate and prostate adenocarcinoma cells. Secretagogin stained 82% (46/56) of benign and 71% (48/68) of prostate adenocarcinomas and co-localized with the NE markers CgA and NSE. The expression of secretagogin is significantly correlated to CgA (P,<,0.001) and NSE (P,<,0.048) in prostate adenocarcinoma and to CgA in normal epithelium (P,<,0.028). Conclusions Secretagogin is a novel NE marker in the prostate with more extended immunoreactivity compared to the NE markers CgA, SYN, and NSE. Secretagogin is widely expressed in prostatic adenocarcinoma as opposed to adenocarcinomas in other organs. Prostate 67: 472,484, 2007. © 2007 Wiley-Liss, Inc. [source] Discrimination between benign and malignant prostate tissue using chromatin texture analysis in 3-D by confocal laser scanning microscopyTHE PROSTATE, Issue 3 2007André Huisman Abstract BACKGROUND Analysis of chromatin texture may improve both the diagnosis and the assessment of the prognosis of prostate cancer. Confocal laser scanning microscopy (CLSM) allows performing measurements in nuclei reconstructed in 3-D. The aim of this study was to evaluate the clinical usefulness of 3-D texture analysis of prostate tissue. METHODS Image stacks of eight prostate cancer sections were obtained by CLSM of both benign and malignant areas. Texture feature values were computed for individual nuclei. The discriminative power of the texture features was established by receiver operating characteristic (ROC) analysis and linear discriminant analysis (LDA). RESULTS Texture features were identified that could discriminate between benign and malignant nuclei. LDA correctly classified 89% of the nuclei of the pooled set of benign and malignant nuclei. CONCLUSIONS 3-D nuclear texture features allow discrimination of most benign and malignant prostate nuclei. We estimate that the classification rates can be increased by improving the image quality. Prostate 67:248,254, 2007. © 2006 Wiley-Liss, Inc. [source] Comparative study of PSMA expression in the prostate of mouse, dog, monkey, and human,THE PROSTATE, Issue 9 2006Saurabh Aggarwal Abstract BACKGROUND Intraprostatic PSMA targeted prodrugs/protoxins are under development in our laboratory. Future toxicologic studies of these therapies require identification of animal models that express PSMA within the prostate. METHOD PSMA enzymatic activity and protein expression was determined. PSMA expression in the prostates of mouse, dog, and monkey were compared to humans by real-time PCR analysis. RESULTS No substrate hydrolysis was observed in dog or monkey prostate homogenates. Monkey prostate was negative for PSMA protein expression. No significant PSMA mRNA levels were detected by real time PCR in mouse, dog, or monkey prostate tissue compared to PSMA negative tissues. CONCLUSIONS PSMA is not expressed in any significant amount in the prostates of mouse, beagle dog, or macaque monkeys in this study but is expressed in high levels by human prostate. These non-human species, therefore, are not suitable toxicologic models to assess prostate damage from PSMA-activated intraprostatic prodrug/protoxin therapies. Prostate 66: 903,910, 2006. © 2006 Wiley-Liss, Inc. [source] Methylation of the ASC gene promoter is associated with aggressive prostate cancerTHE PROSTATE, Issue 7 2006Rachael L. Collard Abstract Background The aim of this study was to investigate the methylation status of apoptosis-associated speck-like protein containing a CARD (ASC; TMS1; PYCARD) in prostate cancer cell lines and human tissues and to determine if those findings correlate with the clinicopathological features of prostate cancer. Methods Genomic DNA was isolated from prostate cell lines and microdissected tissues, bisulfite converted and analyzed by methylation specific polymerase chain reaction (MSP). Expression of ASC in prostate cancer cell lines treated with or without methylation inhibitors was determined by quantitative or qualitative RT-PCR. Results ASC gene expression was silenced or reduced in five prostate cancer cell lines and correlated with methylation status. Treatment of MDAPCa2b prostate cancer cells with the methylation inhibitors 5-aza-2-deoxycitidine and Zebularine reactivated expression of ASC. Of 58 prostate cancer specimens, methylation of the ASC promoter region was present in 65% of primary cancer tissue, 64% (7/11) of cancer-associated high grade-prostatic intraepithelial neoplasia (HG-PIN), and 28% of normal-appearing but adjacent to tumor prostate tissue. While ASC methylation was not related to Gleason score (P,=,0.46) or pathological stage (P,=,0.75), there was a significantly higher frequency of ASC methylation in the adjacent normal tissue for patients with biochemical recurrence (P,=,0.0383). Conclusions Methylation of the ASC gene promoter is both a frequent and early event in prostate cancer carcinogenesis. Surprisingly, methylation of the adjacent normal tissue occurs significantly more often in patients who later undergo biochemical recurrence, suggesting a role for inactivation of the ASC gene in the initial stages of aggressive disease. Prostate © 2006 Wiley-Liss, Inc. [source] T-cell recognition of a prostate specific antigen is not sufficient to induce prostate tissue destructionTHE PROSTATE, Issue 6 2006Jason R. Lees Abstract METHODS The ability of CD8+ T-cells to induce prostate inflammation was examined using a prostate ovalbumin expressing transgenic mouse (POET) and/or adoptive transfer of T-cell receptor (TCR) transgenic T-cells (OT-I) that specifically recognize ovalbumin. Localization of inflammatory cells to prostate tissue was examined following T-cell activation via endogenous prostatic antigen, recombinant type 5 adenovirus carrying the gene coding ovalbumin (Ad5-mOVA), or adoptive transfer of in vitro antigen stimulated OT-I cells. RESULTS Ovalbumin specific OT-I cells were activated by autologous prostate antigen and trafficked to the prostate, but did not induce inflammation unless present in overwhelming numbers (,65% of CD8+ T-cells). Activation of antigen specific CD8+ T-cells in vitro (peptide pulsed antigen presenting cells) or in vivo (Ad5-mOVA) induced transitory prostate inflammation, without induction of prostate pathology, regardless of CD4+ T-cell availability. Inflammation also was observed in OT-I,×,POET mice but again, pathological effects were not observed. CONCLUSIONS T lymphocytes specific for a prostate antigen are capable of inducing inflammatory infiltration of prostatic tissue rapidly following activation, but do not produce pathological prostate injury. Prostate 66:578,590, 2006. © 2005 Wiley-Liss, Inc. [source] Erythropoietin stimulates growth and STAT5 phosphorylation in human prostate epithelial and prostate cancer cellsTHE PROSTATE, Issue 2 2006Laurie Feldman Abstract BACKGROUND Erythropoietin (Epo), the principal regulator of erythroid progenitor survival, growth, and differentiation, initiates its action by binding to its cognate cell surface receptor (EpoR). EpoR have been identified on a variety of non-hematopoietic cells, both normal and malignant, however, little is known about the function of EpoR on malignant cells. METHODS RT-PCR, Western blotting, and immunohistochemistry were used to demonstrate that prostate cancer cells express EpoR at both the gene and protein level. Cell proliferation assays and STAT5 phosphorylation were used to demonstrate Epo's mitogenic action and intracellular signaling, respectively. RESULTS We have demonstrated that transformed prostate epithelial and prostate cancer cell lines, as well as primary prostate tissue, express the EpoR. Importantly, the EpoR on prostate cells are functional, as demonstrated by the observation that each of the cell lines exhibited a dose-dependent proliferative response to Epo, and that Epo triggered STAT5b phosphorylation in the cells. CONCLUSION Human prostatic epithelial cells and prostate cancer cells express functional EpoR, and Epo serves as a growth factor for these cells. These results have implications for our understanding of normal prostatic growth and development and of the pathobiology of human prostate cancer. © 2005 Wiley-Liss, Inc. [source] Evidence for downregulation of calcium signaling proteins in advanced mouse adenocarcinomaTHE PROSTATE, Issue 2 2005Viola C. Ruddat Abstract BACKGROUND Prostate cancer (PCa) is the leading cancer related death in America. Gleason grading is currently the predominant method for prediction, with only few biomarkers available. More biomarkers, especially as they relate to cancer progression are desirable. METHODS The abundance of several important proteins in prostate tissue was compared between wild-type mouse dorsal prostate and well-differentiated transgenic adenocarcinoma mouse prostate (TRAMP) mouse dorsal prostates, and between wild-type mouse dorsal prostate and poorly-differentiated TRAMP mouse tumor tissue. 2DIGE method in conjunction with MALDI-ToF and Western blots was used to determine differential expression. RESULTS In TRAMP dorsal prostates with well-differentiated adenocarcinoma, there were few significant changes in the protein abundances compared to wild-type dorsal prostates, with the exception of increases in proliferating cell nuclear antigen (PCNA) and beta tubulin, two proteins implicated in cell proliferation, and a more than 2-fold increase in Hsp60, a protein involved in the suppression of apoptosis. In the poorly-differentiated tumors, the changes in protein abundance were substantial. While some of those changes could be related to the disappearance of stromal tissue or the appearance of epithelial tissue, other changes in protein abundance were more significant to the cancer development itself. Most notable was the overall decrease in calcium homeostasis proteins with a 10-fold decrease in calreticulin and Hsp70 and a 40-fold decrease in creatine kinase bb in the cancerous tissue. CONCLUSIONS Proteomics of TRAMP mice provide an excellent method to observe changes in protein abundance, revealing changes in pathways during cancer progression. © 2005 Wiley-Liss, Inc. [source] Peroxisomal branched chain fatty acid ,-oxidation pathway is upregulated in prostate cancerTHE PROSTATE, Issue 4 2005Shan Zha Abstract Overexpression of ,-methylacyl-CoA racemase (AMACR), an enzyme involved in branched chain fatty acid ,-oxidation, in prostate cancer has been reported. Here, we report that an enzyme downstream from AMACR in the peroxisomal branched chain fatty acid ,-oxidation pathway,D -bifunctional protein (DBP),is also upregulated in prostate cancer at both mRNA and protein levels, accompanied by increased enzymatic activity. Furthermore, our data suggest that pristanoyl-CoA oxidase (ACOX3), which is expressed at extremely low level in other human organs studied including the liver, might contribute significantly to peroxisomal branched chain fatty acid ,-oxidation in human prostate tissue and some prostate cancer cell lines. In contrast to these results for peroxisomal enzymes, no significant expression changes of mitochondrial fatty acid ,-oxidation enzymes were observed in prostate cancer tissues through comprehensive quantitative RT-PCR screening. These data for the first time provide evidence for the selective over-activation of peroxisomal branched chain fatty acid ,-oxidation in prostate cancer, emphasizing a new metabolic change during prostate oncogenesis. © 2004 Wiley-Liss, Inc. [source] Relative concentrations of hK2/PSA mRNA in benign and malignant prostatic tissueTHE PROSTATE, Issue 4 2005Susanna Lintula Abstract BACKGROUND Prostate-specific antigen (PSA/KLK3) and human kallikrein 2 (hK2/KLK2) belong to the human kallikrein gene family. These two highly homologous genes are specifically expressed in the prostate under androgen control. Expression of these is regulated by similar mechanisms but changes in their relative expression have been observed in prostate cancer. METHODS We determined the relative levels of PSA and hK2 mRNA in benign and malignant prostate tissue using a quantitative reverse transcription-polymerase chain reaction (RT-PCR) method. The mRNA of PSA and hK2 are reverse transcribed and amplified in one reaction with the same primers. RESULTS The variation in the ratio of hK2/PSA mRNA was remarkably small, the difference between the highest and lowest values being three-fold. The ratio was significantly higher in WHO grade 2 compared to normal or benign prostatic hyperplasia tissue (P,=,0.032 and P,=,0.035, respectively) and in grade 3 compared to normal or benign prostatic hyperplasia tissue (P,=,0.006 in both). CONCLUSIONS The new quantitative RT-PCR technique facilitates very accurate quantitation of the relative mRNA levels of homologous genes. Using this method we have shown that the ratio of hK2/PSA mRNA is higher in cancerous than in benign prostatic tissue. © 2004 Wiley-Liss, Inc. [source] FGF17 is an autocrine prostatic epithelial growth factor and is upregulated in benign prostatic hyperplasiaTHE PROSTATE, Issue 1 2004Nathaniel Polnaszek Abstract BACKGROUND Fibroblast growth factors (FGFs) are known to play an important role in the growth of prostatic epithelial cells. Benign prostatic hyperplasia (BPH) is characterized by increased epithelial and stromal proliferation within the transition zone of the prostate. FGF2, FGF7, and FGF9 are expressed in BPH tissue but expression of FGF17 has not been previously characterized in human prostate tissue. METHODS Expression of FGF17 in human prostate tissue and primary cultures of prostatic epithelial and stromal cells was determined by reverse-transcriptase polymerase chain reaction (RT-PCR). Growth response to FGF17 was assessed by addition of recombinant FGF17 to immortalized normal and neoplastic epithelial cell lines and primary cultures of prostatic stromal cells in the presence of insulin. Quantitative analysis of expression of FGF17 relative to keratin 18 and/or ,-actin in normal and hyperplastic prostate and prostate carcinoma was carried out by real-time quantitative RT-PCR. RESULTS FGF17 is expressed by prostatic epithelial cells and can act as an autocrine growth factor for immortalized and neoplastic prostatic epithelial cells. It can also promote stromal proliferation, although only at higher concentrations. Expression of FGF17 per epithelial cell was increased 2-fold in BPH. CONCLUSIONS FGF17 is expressed by normal, hyperplastic, and neoplastic prostatic epithelial cells and can promote epithelial proliferation in an autocrine manner. FGF17 expression is increased 2-fold in BPH and may contribute to the increased epithelial proliferation seen in this disease. © 2004 Wiley-Liss, Inc. [source] | |||||||||||||||||||||||||||||||