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Human Prostate Tissue (human + prostate_tissue)
Selected AbstractsNuclear 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] 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] 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] 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] 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] Purification of the keratan sulfate proteoglycan expressed in prostatic secretory cells and its identification as lumicanTHE PROSTATE, Issue 3 2004John W. Holland Abstract BACKGROUND Secretory epithelial cells of human prostate contain a keratan sulfate proteoglycan (KSPG) associated with the prostatic secretory granules (PSGs). The proteoglycan has not been identified, but like the PSGs, it is lost in the early stages of malignant transformation. METHODS Anion exchange and affinity chromatography were used to purify KSPG from human prostate tissue. Enzymatic deglycosylation was used to remove keratan sulfate (KS). The core protein was isolated using 2D gel electrophoresis, digested in-gel with trypsin, and identified by peptide mass fingerprinting (PMF). RESULTS The purified proteoglycan was detected as a broad smear on Western blots with an apparent molecular weight of 65,95 kDa. The KS moiety was susceptible to digestion with keratanase II and peptide N -glycosidase F defining it as highly sulfated and N-linked to the core protein. The core protein was identified, following deglycosylation and PMF, as lumican and subsequently confirmed by Western blotting using an anti-lumican antibody. CONCLUSIONS The KSPG associated with PSGs in normal prostate epithelium is lumican. While the role of lumican in extracellular matrix is well established, its function in the prostate secretory process is not known. It's potential to facilitate packaging of polyamines in PSGs, to act as a tumor suppressor and to mark the early stages of malignant transformation warrant further investigation. © 2004 Wiley-Liss, Inc. [source] Neuroendocrine differentiation in human prostate tissue: is it detectable and treatable?BJU INTERNATIONAL, Issue 5 2003A. Sciarra First page of article [source] Cytochrome P450 2B6 is a growth-inhibitory and prognostic factor for prostate cancerTHE PROSTATE, Issue 10 2007Jinpei Kumagai Abstract BACKGROUND Cytochrome P450s (CYPs) influence the biological effects of carcinogens, drugs and hormones including testosterones. Among them, Cytochrome P450 2B6 (CYP2B6) plays a critical role in the deactivation of testosterone. In the present study, we examined CYP2B6 expression in human prostate tissues and prostate cancer. METHODS Immunohistochemical analysis was performed in 98 benign and 106 malignant prostate tissues and patients' charts were reviewed for clinical, pathologic and survival data. We also investigated whether stable expression of CYP2B6 in LNCaP (human prostate cancer cell line) influences cellular proliferation. RESULTS CYP2B6 was abundantly expressed in the normal epithelial cells compared to the prostate cancer cells. Significant immunostaining of CYP2B6 was found in 75 of 106 samples (71%), in the cytoplasm of cancerous tissue samples. CYP2B6 immunoreactivity was inversely correlated with high Gleason score (P,<,0.001). Decreased immunoreactivity of CYP2B6 significantly correlated with poor prognosis (P,<,0.0001). Univariate and multivariate hazard analyses revealed a significant correlation of decreased CYP2B6 expression with poor cancer-specific survival (P,=,0.0028 and 0.0142, respectively). Furthermore, overexpression of CYP2B6 in LNCaP cells significantly decreased testosterone-induced proliferation. CONCLUSIONS These results demonstrated that decreased expression of CYP2B6 might play a role in the development of prostate cancer, and be useful as the prognostic predictor for human prostate cancer. Prostate 67: 1029,1037, 2007. © 2007 Wiley-Liss, Inc. [source] Stat3 activation in prostatic carcinomasTHE PROSTATE, Issue 4 2002Rajiv Dhir Abstract BACKGROUND Activated Stat3 is found in various types of immortal cell lines and cancers. We and others have previously demonstrated that Stat3 is constitutively activated in rat and human prostate cancer cell lines, and that Stat3 activation is involved in IL-6-mediated signaling transduction in prostate cancer cells. The aim of this study is to examine quantitative Stat3 activity in benign and malignant human prostate tissues and analyze the association between Stat3 activity levels and the clinical and pathologic parameters. METHODS Stat3 activity levels were analyzed in a total of 104 human primary prostate tissues using electromobility shift assay and immunohistochemical staining for phosphorylated Stat3. The tissue samples used were 42 prostate carcinomas, 42 matched normal prostate tissues from patients with prostatic adenocarcinoma (normal adjacent to tumor), and 20 normal prostate tissues from organ donors. RESULTS Significantly higher levels of constitutive Stat3 activity were detected in both prostate carcinomas and the matched normal prostate tissues adjacent to tumors compared to the normal prostates from donors without prostate cancer. There was no significant difference of Stat3 activity in foci of tumor and normal prostate tissue adjacent to tumor. No correlation was seen between Stat3 activity and Gleason grade or serum PSA levels in samples from prostate carcinomas. CONCLUSIONS These results indicate that Stat3 is constitutively activated in prostate cancer. The high level of Stat3 activity in both the prostate carcinomas and the normal prostate tissues adjacent to tumors suggests that Stat3 activation may occur before detectable histological alterations of the prostate. Prostate 51: 241,246, 2002. © 2002 Wiley-Liss, Inc. [source] Differential expression of estrogen-related receptors , and , (ERR, and ERR,) and their clinical significance in human prostate cancerCANCER SCIENCE, Issue 3 2010Tetsuya Fujimura (Cancer Sci 2010; 101: 646,651) Estrogen-related receptor (ERR) is a nuclear receptor that modulates the estrogen-signaling pathway. Here, we investigated the expression of both ERR, and ERR, in human prostate tissues. Using original rabbit polyclonal anti-ERR, and anti-ERR, antibodies, the expression of ERR, and ERR, was evaluated by immunohistochemical analysis of cancerous lesions (n = 107) and benign foci (n = 92), obtained by radical prostatectomy. Stained slides were evaluated for the proportion of immunoreactive cells and their staining intensity. Total immunoreactivity scores (IR scores; range, 0,8) were calculated as the sum of the proportion and intensity scores. The relationship between the clinicopathological characteristics of the patients and the expression of the three ERRs (ERR,, ERR ,, and ERR ,) was evaluated. IR scores for ERR, and ERR, were significantly lower in cancerous lesions than that in benign foci (P < 0.0001, for both). Clinicopathological analyses revealed that the patients with low ERR, IR scores (,4) tended to show poor cancer-specific survival (P = 0.07). Then, we used data from our previous study (Fujimura T., Int J Cancer, 2007; 120: 2325,30). Patients with a high IR score for ERR, and a low score for ERR, showed significantly poorer cancer-specific survival than those with a low IR score for ERR, and a high score for ERR, (P = 0.0003). We demonstrated the differential expression of ERR, and ERR, in prostate tissue. The combined evaluation of the expression of ERR, and ERR, could be a significant prognostic factor for prostate cancer. [source] | ||||||||||