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Sample records for human prostate tissue

  1. Response of Human Prostate Tissue to Hypofractionated Ionizing Radiation

    DTIC Science & Technology

    2011-07-01

    Summary01-07-2011 Response of Human Prostate Tissue to Hypofractionated Ionizing Radiation Dr. Thomas Sroka University of Arizona Tucson, AZ 85719 The aim...of this proposal is to determine the differences in radiobiological response of human prostate tissue to conventional and hypofractionated ...conventional and hypofractionated ionizing radiation. Data generated in the first year of study has shown that normal prostate tissue and prostate

  2. Enoxacin penetration into human prostatic tissue.

    PubMed Central

    Bergeron, M G; Roy, R; Lessard, C; Foucault, P

    1988-01-01

    Concurrent enoxacin concentrations in serum and prostatic tissue were determined in 14 patients. The mean ratios of enoxacin concentration in tissue over concentration in serum were 1.4 +/- 0.2 (standard error of the mean). The levels in serum and prostatic tissue were above the MICs for most urinary pathogens. PMID:3196004

  3. Response of Human Prostate Tissue to Hypofractionated Ionizing Radiation

    DTIC Science & Technology

    2012-05-01

    hypofractionated ionizing radiation. PRINCIPAL INVESTIGATOR: Thomas C. Sroka, M.D., Ph.D...April 2012 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Response of human prostate tissue to hypofractionated ionizing radiation. 5b. GRANT NUMBER...of this proposal was to determine the differences in radiobiological response of human prostate tissue to conventional and hypofractionated

  4. Prostate tissue stiffness as measured with a resonance sensor system: a study on silicone and human prostate tissue in vitro.

    PubMed

    Jalkanen, Ville; Andersson, Britt M; Bergh, Anders; Ljungberg, Börje; Lindahl, Olof A

    2006-07-01

    Prostate cancer is the most common form of cancer in men in Europe and in the USA. Some prostate tumours are stiffer than the surrounding normal tissue, and it could therefore be of interest to measure prostate tissue stiffness. Resonance sensor technology based on piezoelectric resonance detects variations in tissue stiffness due to a change in the resonance frequency. An impression-controlled resonance sensor system was used to detect stiffness in silicone rubber and in human prostate tissue in vitro using two parameters, both combinations of frequency change and force. Variations in silicone rubber stiffness due to the mixing ratio of the two components could be detected (p<0.05) using both parameters. Measurements on prostate tissue showed that there existed a statistically significant (MANOVA test, p<0.001) reproducible difference between tumour tissue (n=13) and normal healthy tissue (n=98) when studying a multivariate parameter set. Both the tumour tissue and normal tissue groups had variations within them, which were assumed to be related to differences in tissue composition. Other sources of error could be uneven surfaces and different levels of dehydration for the prostates. Our results indicated that the resonance sensor could be used to detect stiffness variations in silicone and in human prostate tissue in vitro. This is promising for the development of a future diagnostic tool for prostate cancer.

  5. Norfloxacin penetration into human renal and prostatic tissues.

    PubMed Central

    Bergeron, M G; Thabet, M; Roy, R; Lessard, C; Foucault, P

    1985-01-01

    Concurrent norfloxacin concentrations in serum, kidney, and prostatic tissue were determined in 14 patients. Mean ratios of norfloxacin concentration in tissue over concentration in serum were 6.6 +/- 2.8 for the kidney and 1.7 +/- 0.2 for the prostate samples. The levels were above the MICs of most urinary pathogens. PMID:3834837

  6. Penetration of orally administered prulifloxacin into human prostate tissue.

    PubMed

    Giberti, Claudio; Gallo, Fabrizio; Rosignoli, Maria T; Ruggieri, Alessandro; Barattè, Simona; Picollo, Rossella; Dionisio, Paolo

    2009-01-01

    Prulifloxacin, a fluoroquinolone antibacterial agent, may be a useful addition to the antimicrobial armamentarium against prostatitis once the ability of its active metabolite, ulifloxacin, to penetrate prostatic tissue has been determined. This study set out to evaluate ulifloxacin penetration into the prostate following administration of the oral fluoroquinolone prodrug prulifloxacin in patients undergoing transurethral resection of the prostate (TURP). This was a phase I, randomized, open-label, single-centre study involving 20 male Caucasian patients (mean age 63.1 years) requiring TURP for treatment of benign prostatic hyperplasia. Sixteen patients were randomized to receive prulifloxacin; the other four patients were not treated (controls) in order to validate the bioanalytical method. Patients in the active treatment groups were randomized to receive one or three once-daily doses of prulifloxacin 600 mg, with the last administration 3 hours prior to surgery. Central/transitional and peripheral zone prostatic tissue samples were obtained from the 6 o'clock and 9 o'clock positions in the prostate, and blood samples were collected concurrently. Ulifloxacin concentrations were determined in the tissue samples and plasma using liquid chromatography-tandem mass spectrometry. Safety was also assessed. Prostatic tissue concentrations of ulifloxacin always exceeded those in plasma. Mean ulifloxacin concentrations measured in samples collected from the 6 o'clock central/transitional zone of the prostate were higher in patients who received prulifloxacin for 3 days than in those who received a single dose. Mean prostatic tissue/plasma ulifloxacin concentration ratios after single and repeated prulifloxacin administration ranged from 3.8 to 7.1 and from 3.9 to 9.5, respectively. The highest mean ratio was found in the 6 o'clock central/transitional zone after repeated dosing. Prostatic levels of ulifloxacin were above the minimum inhibitory concentrations for the most

  7. High risk human papilloma viruses (HPVs) are present in benign prostate tissues before development of HPV associated prostate cancer.

    PubMed

    Glenn, Wendy K; Ngan, Christopher C; Amos, Timothy G; Edwards, Richard J; Swift, Joshua; Lutze-Mann, Louise; Shang, Fei; Whitaker, Noel J; Lawson, James S

    2017-01-01

    Although high risk HPVs are associated with an increased risk of prostate cancer it is not known if they have a causal role. The purpose of this study is to investigate the potential role of human papilloma viruses (HPVs) in prostate cancer. The aims are (i) to investigate the presence and confirm the identity of high risk HPVs in benign prostate tissues prior to the development of HPV positive prostate cancer in the same patients, and (ii) to determine if HPVs are biologically active. We used polymerase chain reaction (PCR) to identify HPVs in specimens from 52 Australian men with benign prostate biopsies who 1 to 10 years later developed prostate cancer. Immunohistochemistry (IHC) was used to assess the expression of HPV E7 oncoproteins, cytokeratin and prostate specific antigen (PSA). We used RNASeq data from The Cancer Genome Atlas (TCGA) to identify possible HPV RNA sequences in prostate cancer. HPV screening using standard PCR was conducted on 28 of the 52 sets of benign and later prostate cancers. HPV L1 genes were identified in 13 (46%) benign and 8 (29%) of 28 later prostate cancers in the same patients. HPV E7 genes were identified in 23 (82%) benign and 19 (68%) of 28 subsequent prostate cancers in the same patients. The same HPV types were present in both the benign and subsequent prostate cancers in 9 sets of specimens. HPV type 16 was identified in 15% of benign and 3% of prostate cancers. HPV type 18 was identified in 26% of benign and 16% of prostate cancers. Small numbers of HPV types 45, 47, 76 and 115 were also identified. High confidence RNA-Seq evidence for high risk HPV types 16 and 18 was identified in 12 (2%) of the 502 TCGA prostate cancer transcriptomes. High risk HPV E7 oncoprotein was positively expressed in 23 (82%) of 28 benign prostate specimens but only in 8 (29%) of 28 of the later prostate cancer specimens. This difference is statistically significant (p = 0.001). Prostate specific antigen (PSA) was more highly expressed in 26

  8. Obesity and prostate cancer: gene expression signature of human periprostatic adipose tissue.

    PubMed

    Ribeiro, Ricardo; Monteiro, Cátia; Catalán, Victoria; Hu, Pingzhao; Cunha, Virgínia; Rodríguez, Amaia; Gómez-Ambrosi, Javier; Fraga, Avelino; Príncipe, Paulo; Lobato, Carlos; Lobo, Francisco; Morais, António; Silva, Vitor; Sanches-Magalhães, José; Oliveira, Jorge; Pina, Francisco; Lopes, Carlos; Medeiros, Rui; Frühbeck, Gema

    2012-09-25

    Periprostatic (PP) adipose tissue surrounds the prostate, an organ with a high predisposition to become malignant. Frequently, growing prostatic tumor cells extend beyond the prostatic organ towards this fat depot. This study aimed to determine the genome-wide expression of genes in PP adipose tissue in obesity/overweight (OB/OW) and prostate cancer patients. Differentially expressed genes in human PP adipose tissue were identified using microarrays. Analyses were conducted according to the donors' body mass index characteristics (OB/OW versus lean) and prostate disease (extra prostatic cancer versus organ confined prostate cancer versus benign prostatic hyperplasia). Selected genes with altered expression were validated by real-time PCR. Ingenuity Pathway Analysis (IPA) was used to investigate gene ontology, canonical pathways and functional networks. In the PP adipose tissue of OB/OW subjects, we found altered expression of genes encoding molecules involved in adipogenic/anti-lipolytic, proliferative/anti-apoptotic, and mild immunoinflammatory processes (for example, FADS1, down-regulated, and LEP and ANGPT1, both up-regulated). Conversely, in the PP adipose tissue of subjects with prostate cancer, altered genes were related to adipose tissue cellular activity (increased cell proliferation/differentiation, cell cycle activation and anti-apoptosis), whereas a downward impact on immunity and inflammation was also observed, mostly related to the complement (down-regulation of CFH). Interestingly, we found that the microRNA MIRLET7A2 was overexpressed in the PP adipose tissue of prostate cancer patients. Obesity and excess adiposity modified the expression of PP adipose tissue genes to ultimately foster fat mass growth. In patients with prostate cancer the expression profile of PP adipose tissue accounted for hypercellularity and reduced immunosurveillance. Both findings may be liable to promote a favorable environment for prostate cancer progression.

  9. Obesity and prostate cancer: gene expression signature of human periprostatic adipose tissue

    PubMed Central

    2012-01-01

    Background Periprostatic (PP) adipose tissue surrounds the prostate, an organ with a high predisposition to become malignant. Frequently, growing prostatic tumor cells extend beyond the prostatic organ towards this fat depot. This study aimed to determine the genome-wide expression of genes in PP adipose tissue in obesity/overweight (OB/OW) and prostate cancer patients. Methods Differentially expressed genes in human PP adipose tissue were identified using microarrays. Analyses were conducted according to the donors' body mass index characteristics (OB/OW versus lean) and prostate disease (extra prostatic cancer versus organ confined prostate cancer versus benign prostatic hyperplasia). Selected genes with altered expression were validated by real-time PCR. Ingenuity Pathway Analysis (IPA) was used to investigate gene ontology, canonical pathways and functional networks. Results In the PP adipose tissue of OB/OW subjects, we found altered expression of genes encoding molecules involved in adipogenic/anti-lipolytic, proliferative/anti-apoptotic, and mild immunoinflammatory processes (for example, FADS1, down-regulated, and LEP and ANGPT1, both up-regulated). Conversely, in the PP adipose tissue of subjects with prostate cancer, altered genes were related to adipose tissue cellular activity (increased cell proliferation/differentiation, cell cycle activation and anti-apoptosis), whereas a downward impact on immunity and inflammation was also observed, mostly related to the complement (down-regulation of CFH). Interestingly, we found that the microRNA MIRLET7A2 was overexpressed in the PP adipose tissue of prostate cancer patients. Conclusions Obesity and excess adiposity modified the expression of PP adipose tissue genes to ultimately foster fat mass growth. In patients with prostate cancer the expression profile of PP adipose tissue accounted for hypercellularity and reduced immunosurveillance. Both findings may be liable to promote a favorable environment for

  10. Human periprostatic adipose tissue promotes prostate cancer aggressiveness in vitro

    PubMed Central

    2012-01-01

    Background Obesity is associated with prostate cancer aggressiveness and mortality. The contribution of periprostatic adipose tissue, which is often infiltrated by malignant cells, to cancer progression is largely unknown. Thus, this study aimed to determine if periprostatic adipose tissue is linked with aggressive tumor biology in prostate cancer. Methods Supernatants of whole adipose tissue (explants) or stromal vascular fraction (SVF) from paired fat samples of periprostatic (PP) and pre-peritoneal visceral (VIS) anatomic origin from different donors were prepared and analyzed for matrix metalloproteinases (MMPs) 2 and 9 activity. The effects of those conditioned media (CM) on growth and migration of hormone-refractory (PC-3) and hormone-sensitive (LNCaP) prostate cancer cells were measured. Results We show here that PP adipose tissue of overweight men has higher MMP9 activity in comparison with normal subjects. The observed increased activities of both MMP2 and MMP9 in PP whole adipose tissue explants, likely reveal the contribution of adipocytes plus stromal-vascular fraction (SVF) as opposed to SVF alone. MMP2 activity was higher for PP when compared to VIS adipose tissue. When PC-3 cells were stimulated with CM from PP adipose tissue explants, increased proliferative and migratory capacities were observed, but not in the presence of SVF. Conversely, when LNCaP cells were stimulated with PP explants CM, we found enhanced motility despite the inhibition of proliferation, whereas CM derived from SVF increased both cell proliferation and motility. Explants culture and using adipose tissue of PP origin are most effective in promoting proliferation and migration of PC-3 cells, as respectively compared with SVF culture and using adipose tissue of VIS origin. In LNCaP cells, while explants CM cause increased migration compared to SVF, the use of PP adipose tissue to generate CM result in the increase of both cellular proliferation and migration. Conclusions Our

  11. Long term organ culture of human prostate tissue in a NASA-designed rotating wall bioreactor

    NASA Technical Reports Server (NTRS)

    Margolis, L.; Hatfill, S.; Chuaqui, R.; Vocke, C.; Emmert-Buck, M.; Linehan, W. M.; Duray, P. H.

    1999-01-01

    PURPOSE: To maintain ex vivo integral prostatic tissue including intact stromal and ductal elements using the NASA-designed Rotating Wall Vessel (RWV) which maintains colocalized cells in an environment that promotes both three-dimensional cellular interactions together with the uniform mass transfer of nutrients and metabolic wastes. MATERIALS AND METHODS: Samples of normal prostate were obtained as a byproduct of transurethral prostatectomy or needle biopsy. Prostatic tissue dissected into small 1 x 1 mm. blocks was cultured in the Rotating Wall Vessel (RWV) Bioreactor for various time periods and analyzed using histological, immunochemical, and total cell RNA assays. RESULTS: We report the long term maintenance of benign explanted human prostate tissue grown in simple culture medium, under the simulated microgravity conditions afforded by the RWV bioreactor. Mesenchymal stromal elements including blood vessels and architecturally preserved tubuloglandular acini were maintained for a minimum of 28 days. Cytokeratins, vimentin and TGF-beta2 receptor and ligand were preserved through the entire culture period as revealed by immunocytochemistry. Prostatic acid phosphatase (PAP) was continuously expressed during the culture period, although somewhat decreased. Prostatic specific antigen (PSA) and its transcript were down regulated over time of culture. Prostatic carcinoma cells from the TSU cell line were able to invade RWV-cultured benign prostate tissue explants. CONCLUSIONS: The RWV bioreactor represents an additional new technology for culturing prostate tissue for further investigations concerning the basic physiology and pathobiology of this clinically important tissue.

  12. Long term organ culture of human prostate tissue in a NASA-designed rotating wall bioreactor.

    PubMed

    Margolis, L; Hatfill, S; Chuaqui, R; Vocke, C; Emmert-Buck, M; Linehan, W M; Duray, P H

    1999-01-01

    To maintain ex vivo integral prostatic tissue including intact stromal and ductal elements using the NASA-designed Rotating Wall Vessel (RWV) which maintains colocalized cells in an environment that promotes both three-dimensional cellular interactions together with the uniform mass transfer of nutrients and metabolic wastes. Samples of normal prostate were obtained as a byproduct of transurethral prostatectomy or needle biopsy. Prostatic tissue dissected into small 1 x 1 mm. blocks was cultured in the Rotating Wall Vessel (RWV) Bioreactor for various time periods and analyzed using histological, immunochemical, and total cell RNA assays. We report the long term maintenance of benign explanted human prostate tissue grown in simple culture medium, under the simulated microgravity conditions afforded by the RWV bioreactor. Mesenchymal stromal elements including blood vessels and architecturally preserved tubuloglandular acini were maintained for a minimum of 28 days. Cytokeratins, vimentin and TGF-beta2 receptor and ligand were preserved through the entire culture period as revealed by immunocytochemistry. Prostatic acid phosphatase (PAP) was continuously expressed during the culture period, although somewhat decreased. Prostatic specific antigen (PSA) and its transcript were down regulated over time of culture. Prostatic carcinoma cells from the TSU cell line were able to invade RWV-cultured benign prostate tissue explants. The RWV bioreactor represents an additional new technology for culturing prostate tissue for further investigations concerning the basic physiology and pathobiology of this clinically important tissue.

  13. Long term organ culture of human prostate tissue in a NASA-designed rotating wall bioreactor

    NASA Technical Reports Server (NTRS)

    Margolis, L.; Hatfill, S.; Chuaqui, R.; Vocke, C.; Emmert-Buck, M.; Linehan, W. M.; Duray, P. H.

    1999-01-01

    PURPOSE: To maintain ex vivo integral prostatic tissue including intact stromal and ductal elements using the NASA-designed Rotating Wall Vessel (RWV) which maintains colocalized cells in an environment that promotes both three-dimensional cellular interactions together with the uniform mass transfer of nutrients and metabolic wastes. MATERIALS AND METHODS: Samples of normal prostate were obtained as a byproduct of transurethral prostatectomy or needle biopsy. Prostatic tissue dissected into small 1 x 1 mm. blocks was cultured in the Rotating Wall Vessel (RWV) Bioreactor for various time periods and analyzed using histological, immunochemical, and total cell RNA assays. RESULTS: We report the long term maintenance of benign explanted human prostate tissue grown in simple culture medium, under the simulated microgravity conditions afforded by the RWV bioreactor. Mesenchymal stromal elements including blood vessels and architecturally preserved tubuloglandular acini were maintained for a minimum of 28 days. Cytokeratins, vimentin and TGF-beta2 receptor and ligand were preserved through the entire culture period as revealed by immunocytochemistry. Prostatic acid phosphatase (PAP) was continuously expressed during the culture period, although somewhat decreased. Prostatic specific antigen (PSA) and its transcript were down regulated over time of culture. Prostatic carcinoma cells from the TSU cell line were able to invade RWV-cultured benign prostate tissue explants. CONCLUSIONS: The RWV bioreactor represents an additional new technology for culturing prostate tissue for further investigations concerning the basic physiology and pathobiology of this clinically important tissue.

  14. Tissue specific and androgen-regulated expression of human prostate-specific transglutaminase.

    PubMed Central

    Dubbink, H J; Verkaik, N S; Faber, P W; Trapman, J; Schröder, F H; Romijn, J C

    1996-01-01

    Transglutaminases (TGases) are calcium-dependent enzymes catalysing the post-translational cross-linking of proteins. In the prostate at least two TGases are present, the ubiquitously expressed tissue-type TGase (TGC), and a prostate-restricted TGase (TGP). This paper deals with the molecular cloning and characterization of the cDNA encoding the human prostate TGase (hTGP). For this purpose we have screened a human prostate cDNA library with a probe from the active-site region of TGC. The largest isolated cDNA contained an open reading frame encoding a protein of 684 amino acids with a predicted molecular mass of 77 kDa as confirmed by in vitro transcription-translation and subsequent SDS/PAGE. The hTGP gene was tissue-specifically expressed in the prostate, yielding an mRNA of approx. 3.5 kb. Furthermore, a 3-fold androgen-induced upregulation of hTGP mRNA expression has been demonstrated in the recently developed human prostate cancer cell line, PC346C. Other well established human prostate cancer cell lines, LNCaP and PC-3, showed no detectable hTGP mRNA expression on a Northern bolt. The gene coding for prostate TGase was assigned to chromosome 3. PMID:8645175

  15. Evidence for a Proapoptotic Role of Matrix Metalloproteinase-26 in Human Prostate Cancer Cells and Tissues

    PubMed Central

    Khamis, Zahraa I.; Iczkowski, Kenneth A.; Man, Yan-Gao; Bou-Dargham, Mayassa J.; Sang, Qing-Xiang Amy

    2016-01-01

    Matrix metalloproteinases (MMPs) play intricate roles in cancer progression; some promote invasion and angiogenesis while others suppress tumor growth. For example, human MMP-26/endometase/matrilysin-2 was reported to be either protective or pro-tumorigenic. Our previous reports suggested pro-invasion and anti-inflammation properties in prostate cancer. Here, we provide evidence for a protective role of MMP-26 in the prostate. MMP-26 expression levels in androgen-repressed human prostate cancer (ARCaP) cells, transfected with sense or anti-sense MMP-26 cDNA, are directly correlated with those of the pro-apoptotic marker Bax. Immunohistochemical staining of prostate cancer tissue samples shows similar protein expression patterns, correlating the expression levels of MMP-26 and Bax in benign, neoplastic, and invasive prostate cancer tissues. The MMP-26 protein levels were upregulated in high grade prostate intraepithelial neoplasia (HGPIN) and decreased during the course of disease progression. Further analysis using an indirect terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay showed that many tumor cells expressing MMP-26 were undergoing apoptosis. This study showed that the high level of MMP-26 expression is positively correlated with the presence of apoptotic cells. This pro-apoptotic role of MMP-26 in human prostate cancer cells and tissues may enhance our understanding of the paradoxical roles of MMP-26 in tumor invasion and progression. PMID:26722363

  16. Harvesting Human Prostate Tissue Material and Culturing Primary Prostate Epithelial Cells.

    PubMed

    Frame, Fiona M; Pellacani, Davide; Collins, Anne T; Maitland, Norman J

    2016-01-01

    In order to fully explore the biology of a complex solid tumor such as prostate cancer, it is desirable to work with patient tissue. Only by working with cells from a tissue can we take into account patient variability and tumor heterogeneity. Cell lines have long been regarded as the workhorse of cancer research and it could be argued that they are of most use when considered within a panel of cell lines, thus taking into account specified mutations and variations in phenotype between different cell lines. However, often very different results are obtained when comparing cell lines to primary cells cultured from tissue. It stands to reason that cells cultured from patient tissue represents a close-to-patient model that should and does produce clinically relevant data. This chapter aims to illustrate the methods of processing, storing and culturing cells from prostate tissue, with a description of potential uses.

  17. Quantification of Protein Signatures in Archived Human Prostate Tissues Using Shotgun Proteomic Methods

    DTIC Science & Technology

    2011-06-01

    proteins were subsequently incubated with wheat - germ agglutinin (WGA) and con canavalin- A (ConA) beads, washed, and el uted with sol uble n-acetyl...prostate radial prostatectomies and have focused on optimizing protocols to extract and profile proteins in matched normal and dise ased tissue s...human prostate cancer using label-free, quantitative mass spectrometry. Last year we were able to extract up to 1 00 micrograms of total protein

  18. Prevention of human PC-346C prostate cancer growth in mice by a xenogeneic tissue vaccine.

    PubMed

    Suckow, Mark A; Rosen, Elliot D; Wolter, William R; Sailes, Valerie; Jeffrey, Randy; Tenniswood, Martin

    2007-08-01

    Vaccination, as an approach to prostate cancer, has largely focused on immunotherapy utilizing specific molecules or allogeneic cells. Such methods are limited by the focused antigenic menu presented to the immune system and by immunotolerance to antigens recognized as "self". To examine if a xenogeneic tissue vaccine could stimulate protective immunity in a human prostate cancer cell line, a vaccine was produced by glutaraldehyde fixation of harvested PAIII prostate cancer cells tumors (GFT cell vaccine) from Lobund-Wistar rats. Immunocompetent Ncr-Foxn1 mice were vaccinated with the GFT cell vaccine four times, 7 days apart. The control animals were either not vaccinated or vaccinated with media or glutaraldehyde-fixed PC346C human prostate cancer cells and adjuvant. About 8 days after the final boost, serum and spleens were harvested. The splenocytes were co-incubated with PC346C cells and then transplanted orthotopically into sygneneic immunodeficient nude mice. About 10 weeks later, the prostates were weighed and sampled for histolologic examination. The spleens were harvested from additional mice, and the splenocytes were cultured, either with or without pulsing by GFT cells, and the supernatants harvested 72 h later for cytokine analysis. Results showed that vaccination with GFT cells resulted in increased serum antibody to a PAIII cell lysate; reduced weight of the prostate/seminal vesicle complex and reduced incidence of prostate cancer in nude mice; increased splenocyte supernatant levels of TNF-alpha, IL-2, IFN-gamma and IL-12, cytokines associated with Th1 immunity; and increased splenocyte supernatant levels of IL-4 and IL-10, cytokines associated with Th2 immunity. In summary, the results suggest that use of a xenogeneic tissue vaccine can stimulate protective immunity against human prostate cancer cells.

  19. In vitro study on the vaporization ratio of 2-microm laser in human prostatic tissue.

    PubMed

    Yang, Yong; Sun, Dongchong; Wei, Zhitao; Xu, Feng; Hong, Baofa; Zhang, Xu

    2010-04-01

    In this study, the vaporization ratio of the 2-mum laser in the prostatic tissue with benign prostatic hyperplasia was examined in vitro, to explore a technique to estimate the clearance rate of prostatic tissue during the transurethral vaporesection of the prostate. A total of 9 fresh prostatic tissue specimens were obtained by open surgery and the wet weight of the prostatic tissue were measured immediately after the sample collection. Under the simulated conditions of transurethral vaporesection of the prostate by 2-microm laser, each prostate gland was completely vaporesected into fragments with a diameter of less than 1.0 cm in vitro. After the vaporesection, the whole fragments of prostatic tissue were collected and measured. Then the lost weight of prostatic tissue, the weight of the collected prostatic tissue and the ratio of the lost weight of prostatic tissue to the wet weight of the prostate glandular organ specimen were calculated. The correlation between the weight of collected prostatic tissue and the weight of the whole glandular organ was analyzed. All the experimental procedures were carried out by one operator. Wet weight of the prostatic gland specimen and the weight of the harvested prostatic tissues after the procedure were recorded. With respect to the wet weight of prostate gland specimen, the percentage of the weight of collected prostatic tissue was (34.45 + or - 1.51) %, and the percentage of the lost weight of prostatic tissue was (65.55 + or - 1.51)%. Satisfactory linear relationship was observed between the weight of collected prostatic tissue and the wet weight of prostate gland specimen [y = 3.245 x -6.475 (t=15.097, P=0.000)]. It is concluded that under the simulated conditions of transurethral vaporesection of the prostate by 2-mum laser, the vaporization ratio of prostatic tissue can be calculated on the basis of the weight of collected prostatic tissue, and thereby the clearance of prostatic tissue during the formal operation by 2

  20. Selective expression of myosin IC Isoform A in mouse and human cell lines and mouse prostate cancer tissues.

    PubMed

    Ihnatovych, Ivanna; Sielski, Neil L; Hofmann, Wilma A

    2014-01-01

    Myosin IC is a single headed member of the myosin superfamily. We recently identified a novel isoform and showed that the MYOIC gene in mammalian cells encodes three isoforms (isoforms A, B, and C). Furthermore, we demonstrated that myosin IC isoform A but not isoform B exhibits a tissue specific expression pattern. In this study, we extended our analysis of myosin IC isoform expression patterns by analyzing the protein and mRNA expression in various mammalian cell lines and in various prostate specimens and tumor tissues from the transgenic mouse prostate (TRAMP) model by immunoblotting, qRT-PCR, and by indirect immunohistochemical staining of paraffin embedded prostate specimen. Analysis of a panel of mammalian cell lines showed an increased mRNA and protein expression of specifically myosin IC isoform A in a panel of human and mouse prostate cancer cell lines but not in non-cancer prostate or other (non-prostate-) cancer cell lines. Furthermore, we demonstrate that myosin IC isoform A expression is significantly increased in TRAMP mouse prostate samples with prostatic intraepithelial neoplasia (PIN) lesions and in distant site metastases in lung and liver when compared to matched normal tissues. Our observations demonstrate specific changes in the expression of myosin IC isoform A that are concurrent with the occurrence of prostate cancer in the TRAMP mouse prostate cancer model that closely mimics clinical prostate cancer. These data suggest that elevated levels of myosin IC isoform A may be a potential marker for the detection of prostate cancer.

  1. Dual-modality probe intended for prostate cancer detection combining Raman spectroscopy and tactile resonance technology--discrimination of normal human prostate tissues ex vivo.

    PubMed

    Nyberg, M; Jalkanen, V; Ramser, K; Ljungberg, B; Bergh, A; Lindahl, O A

    2015-04-01

    Prostate cancer is the most common cancer for men in the western world. For the first time, a dual-modality probe, combining Raman spectroscopy and tactile resonance technology, has been used for assessment of fresh human prostate tissue. The study investigates the potential of the dual-modality probe by testing its ability to differentiate prostate tissue types ex vivo. Measurements on four prostates show that the tactile resonance modality was able to discriminate soft epithelial tissue and stiff stroma (p < 0.05). The Raman spectra exhibited a strong fluorescent background at the current experimental settings. However, stroma could be discerned from epithelia by integrating the value of the spectral background. Combining both parameters by a stepwise analysis resulted in 100% sensitivity and 91% specificity. Although no cancer tissue was analysed, the results are promising for further development of the instrument and method for discriminating prostate tissues and cancer.

  2. Robust HPLC-MS/MS method for levofloxacin and ciprofloxacin determination in human prostate tissue.

    PubMed

    Szerkus, O; Jacyna, J; Gibas, A; Sieczkowski, M; Siluk, D; Matuszewski, M; Kaliszan, R; Markuszewski, M J

    2017-01-05

    Fluoroquinolones are the drugs of choice in the prevention of bacterial infections after transrectal ultrasound guided prostate biopsy. In order to improve assessment of antibacterial efficacy in the target tissue a simple, selective, rapid and robust HPLC-ESI-MS/MS method for the determination of levofloxacin and ciprofloxacin concentrations in human prostate bioptates was developed and validated. Preparation procedure for prostate samples (10mg) was carried out using homogenization and filtration steps. Analyses were performed within 3.5min using RP C18 column in the isocratic elution mode with mobile phase composed of a mixture of 0.1% formic acid aqueous solution and 0.1% formic acid methanol solution (v/v; 79:21). The method was linear between 0.3μg/g and 15μg/g for levofloxacin and ciprofloxacin with coefficient of correlation (r) ≥0.999. The limit of detection and the limit of quantification for levofloxacin were 0.06μg/g and 0.2μg/g and for ciprofloxacin were 0.04μg/g and 0.13μg/g, respectively. Average concentrations (±SD) of levofloxacin and ciprofloxacin obtained from patients tissue were 5.4±2.2μg/g and 3.9±1.5μg/g, respectively. Additionally, during validation procedure a novel, experimental design approach was applied for the robustness study. For evaluation of analytical method robustness, Plackett-Burman design was employed and for sample preparation method robustness Fractional Factorial design was used. The developed and validated method was successfully applied to examine prostate tissue samples obtained from patients enrolled into a clinical study. Up to now, there has been no other HPLC-ESI-MS/MS method reported for the simultaneous determination of levofloxacin and ciprofloxacin in human prostatic tissue. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Analysis of XMRV integration sites from human prostate cancer tissues suggests PCR contamination rather than genuine human infection.

    PubMed

    Garson, Jeremy A; Kellam, Paul; Towers, Greg J

    2011-02-25

    XMRV is a gammaretrovirus associated in some studies with human prostate cancer and chronic fatigue syndrome. Central to the hypothesis of XMRV as a human pathogen is the description of integration sites in DNA from prostate tumour tissues. Here we demonstrate that 2 of 14 patient-derived sites are identical to sites cloned in the same laboratory from experimentally infected DU145 cells. Identical integration sites have never previously been described in any retrovirus infection. We propose that the patient-derived sites are the result of PCR contamination. This observation further undermines the notion that XMRV is a genuine human pathogen.

  4. Prostate specific membrane antigen (PSM) is expressed in various human tissues: implication for the use of PSM reverse transcription polymerase chain reaction to detect hematogenous prostate cancer spread.

    PubMed

    Renneberg, H; Friedetzky, A; Konrad, L; Kurek, R; Weingärtner, K; Wennemuth, G; Tunn, U W; Aumüller, G

    1999-01-01

    Detection of prostate-specific membrane antigen (PSM)-mRNA expression in blood samples using reverse transcription polymerase chain reaction (RT-PCR) is discussed as a new diagnostic marker of circulating micrometastases in prostate cancer patients. We applied the RT-PCR technique to different human tissues and obtained positive signals for PSM transcripts in human genital and multiple extra-genital tissue sites. The cDNAs were prepared from different human tissues and prostatic cell lines. RT-PCR and nested RT-PCR for PSM was performed with primers derived from the published PSM cDNA. The RT-PCR fragments obtained were cloned and showed 100% sequence homology to PSM. Southern blot hybridization with labeled probes was used to confirm the specificity of the amplicons. In addition to the known PSM expression in the human brain, PSM-mRNA was detected in cDNA isolated from human testis, epididymis and seminal vesicles and in the PC-3 prostatic cancer cell line. Furthermore, we found PSM-mRNA in heart, liver, lung, kidney, spleen, and thyroid gland. The results indicate that PSM expression is not restricted to the prostate gland, but represents a more general component of genital and extra-genital human tissues. This must be considered when RT-PCR and nested RT-PCR screening for PSM expression is performed as a diagnostic measure in blood from prostate cancer patients.

  5. Investigation of scattering coefficients and anisotropy factors of human cancerous and normal prostate tissues using Mie theory

    NASA Astrophysics Data System (ADS)

    Pu, Yang; Chen, Jun; Wang, Wubao

    2014-02-01

    The scattering coefficient, μs, the anisotropy factor, g, the scattering phase function, p(θ), and the angular dependence of scattering intensity distributions of human cancerous and normal prostate tissues were systematically investigated as a function of wavelength, scattering angle and scattering particle size using Mie theory and experimental parameters. The Matlab-based codes using Mie theory for both spherical and cylindrical models were developed and applied for studying the light propagation and the key scattering properties of the prostate tissues. The optical and structural parameters of tissue such as the index of refraction of cytoplasm, size of nuclei, and the diameter of the nucleoli for cancerous and normal human prostate tissues obtained from the previous biological, biomedical and bio-optic studies were used for Mie theory simulation and calculation. The wavelength dependence of scattering coefficient and anisotropy factor were investigated in the wide spectral range from 300 nm to 1200 nm. The scattering particle size dependence of μs, g, and scattering angular distributions were studied for cancerous and normal prostate tissues. The results show that cancerous prostate tissue containing larger size scattering particles has more contribution to the forward scattering in comparison with the normal prostate tissue. In addition to the conventional simulation model that approximately considers the scattering particle as sphere, the cylinder model which is more suitable for fiber-like tissue frame components such as collagen and elastin was used for developing a computation code to study angular dependence of scattering in prostate tissues. To the best of our knowledge, this is the first study to deal with both spherical and cylindrical scattering particles in prostate tissues.

  6. Variations in activin receptor, inhibin/activin subunit and follistatin mRNAs in human prostate tumour tissues

    PubMed Central

    Schaik, R H N van; Wierikx, C D J; Timmerman, M A; Oomen, M H; Weerden, W M van; Kwast, T H van der; Steenbrugge, G J van; Jong, F H de

    1999-01-01

    The possible role of activin in the regulation of malignant prostatic growth was studied using RNAase protection assays of activin receptors, inhibin/activin subunits and follistatin mRNAs in the human prostatic carcinoma cell lines LNCaP-FGC, -R and -LNO, in human prostatic carcinoma xenografts and in human prostatic tissue. Activin receptor types IA (ActRIA), IB (ActRIB), IIA (ActRIIA) and IIB (ActRIIB) mRNAs were generally expressed in prostate pithelial cells, with significantly lower levels of ActRIB mRNA in prostate tumour aterial when compared to non-malignant tissue (P< 0.05; Mann–Whitney U -test). Inhibin/activin βA- and βB-subunit mRNA expression was also found in prostate tissue. Androgen-independent xenografts expressed significantly lower amounts of βB-subunit mRNA when compared to androgen-dependent xenografts (P< 0.05). While βB-subunit mRNA was expressed by LNCaP-FGC and -LNO cells, virtually no expression was found in the androgen-independent LNCaP-R line. Inhibin α-subunit mRNA levels were low or undetectable in all samples investigated. Follistatin mRNA was undetectable in LNCaP-sublines, while low levels were found in prostatic tissues. In androgen-independent LNCaP-R cells, activin inhibited cell growth in a dose-dependent manner. These results suggest that prostate tumour progression is accompanied by a decrease of the inhibitory effect of locally produced activin by either a decrease in the expression of activin βB-subunit mRNA or by a decrease of ActRIB mRNA levels. © 2000 Cancer Research Campaign PMID:10638976

  7. High-resolution NMR spectroscopy of human body fluids and tissues in relation to prostate cancer.

    PubMed

    Kumar, Virendra; Dwivedi, Durgesh K; Jagannathan, Naranamangalam R

    2014-01-01

    High-resolution NMR spectroscopic studies of prostate tissue extracts, prostatic fluid, seminal fluid, serum and urine can be used for the detection of prostate cancer, based on the differences in their metabolic profiles. Useful diagnostic information is obtained by the detection or quantification of as many metabolites as possible and comparison with normal samples. Only a few studies have shown the potential of high-resolution in vitro NMR of prostate tissues. A survey of the literature has revealed that studies on body fluids, such as urine and serum, in relation to prostate cancer are rare. In addition, the potential of NMR of nuclei other than (1)H, such as (13)C and (31)P, has not been exploited fully. The metabolomic analysis of metabolites, detected by high-resolution NMR, may help to identify metabolites which could serve as useful biomarkers for prostate cancer detection. Such NMR-derived biomarkers would not only help in prostate cancer detection and in understanding the in vivo MRS metabolic profile, but also to investigate the biochemical and metabolic changes associated with cancer. Here, we review the published research work on body fluids in relation to prostate and prostate tissue extracts, and highlight the potential of such studies for future work. Copyright © 2013 John Wiley & Sons, Ltd.

  8. Protein profiling of isolated leukocytes, myofibroblasts, epithelial, Basal, and endothelial cells from normal, hyperplastic, cancerous, and inflammatory human prostate tissues.

    PubMed

    Khamis, Zahraa I; Iczkowski, Kenneth A; Sahab, Ziad J; Sang, Qing-Xiang Amy

    2010-06-15

    In situ neoplastic prostate cells are not lethal unless they become invasive and metastatic. For cells to become invasive, the prostate gland must undergo degradation of the basement membrane and disruption of the basal cell layer underneath the luminal epithelia. Although the roles of proteinases in breaking down the basement membrane have been well-studied, little is known about the factors that induce basal cell layer disruption, degeneration, and its eventual disappearance in invasive cancer. It is hypothesized that microenvironmental factors may affect the degradation of the basal cell layer, which if protected may prevent tumor progression and invasion. In this study, we have revealed differential protein expression patterns between epithelial and stromal cells isolated from different prostate pathologies and identified several important epithelial and stromal proteins that may contribute to inflammation and malignant transformation of human benign prostate tissues to cancerous tissues using matrix-assisted laser desorption ionization time-of-flight mass spectrometry and proteomics methods. Cellular retinoic acid-binding protein 2 was downregulated in basal cells of benign prostate. Caspase-1 and interleukin-18 receptor 1 were highly expressed in leukocytes of prostate cancer. Proto-oncogene Wnt-3 was downregulated in endothelial cells of prostatitis tissue and tyrosine phosphatase non receptor type 1 was only found in normal and benign endothelial cells. Poly ADP-ribose polymerase 14 was downregulated in myofibroblasts of prostatitis tissue. Interestingly, integrin alpha-6 was upregulated in epithelial cells but not detected in myofibroblasts of prostate cancer. Further validation of these proteins may generate new strategies for the prevention of basal cell layer disruption and subsequent cancer invasion.

  9. Penetration of piperacillin-tazobactam into human prostate tissue and dosing considerations for prostatitis based on site-specific pharmacokinetics and pharmacodynamics.

    PubMed

    Kobayashi, Ikuo; Ikawa, Kazuro; Nakamura, Kogenta; Nishikawa, Genya; Kajikawa, Keishi; Yoshizawa, Takahiko; Watanabe, Masahito; Kato, Yoshiharu; Zennami, Kenji; Kanao, Kent; Tobiume, Motoi; Yamada, Yoshiaki; Mitsui, Kenji; Narushima, Masahiro; Morikawa, Norifumi; Sumitomo, Makoto

    2015-08-01

    This study aimed to investigate the penetration of PIPC-TAZ into human prostate, and to assess effectiveness of PIPC-TAZ against prostatitis by evaluating site-specific PK-PD. Patients with prostatic hypertrophy (n = 47) prophylactically received a 0.5 h infusion of PIPC-TAZ (8:1.2-0.25 g or 4-0.5 g) before transurethral resection of the prostate. PIPC-TAZ concentrations in plasma (0.5-5 h) and prostate tissue (0.5-1.5 h) were analyzed with a three-compartment PK model. The estimated model parameters were, then used to estimate the drug exposure time above the minimum inhibitory concentration for bacteria (T > MIC, the PD indicator for antibacterial effects) in prostate tissue for six PIPC-TAZ regimens (2.25 or 4.5 g; once, twice, three times or four times daily; 0.5 h infusions). Prostate tissue/plasma ratio of PIPC was about 36% both for the maximum drug concentration (Cmax) and the area under the drug concentration-time curve (AUC). Against MIC distributions for isolates of Escherichia coli, Klebsiella species and Proteus species, regimens of 4.5 g twice daily and 2.25 g three times daily achieved a >90% probability of attaining the bacteriostatic target for PIPC (30% T > MIC) in prostate tissue; regimens of 4.5 g three times daily and 2.25 g four times daily achieved a >90% probability of attaining the bactericidal target for PIPC (50% T > MIC) in prostate tissue. However, against Pseudomonas aeruginosa isolates, none of the tested regimens achieved a >90% probability. PIPC-TAZ is appropriate for the treatment of prostatitis from the site-specific PK-PD perspective. Copyright © 2015. Published by Elsevier Ltd.

  10. Expression of spermidine/spermine N(1) -acetyl transferase (SSAT) in human prostate tissues is related to prostate cancer progression and metastasis.

    PubMed

    Huang, Wei; Eickhoff, Jens C; Mehraein-Ghomi, Farideh; Church, Dawn R; Wilding, George; Basu, Hirak S

    2015-08-01

    Prostate cancer (PCa) in many patients remains indolent for the rest of their lives, but in some patients, it progresses to lethal metastatic disease. Gleason score is the current clinical method for PCa prognosis. It cannot reliably identify aggressive PCa, when GS is ≤ 7. It is shown that oxidative stress plays a key role in PCa progression. We have shown that in cultured human PCa cells, an activation of spermidine/spermine N(1) -acetyl transferase (SSAT; EC 2.3.1.57) enzyme initiates a polyamine oxidation pathway and generates copious amounts of reactive oxygen species in polyamine-rich PCa cells. We used RNA in situ hybridization and immunohistochemistry methods to detect SSAT mRNA and protein expression in two tissue microarrays (TMA) created from patient's prostate tissues. We analyzed 423 patient's prostate tissues in the two TMAs. Our data show that there is a significant increase in both SSAT mRNA and the enzyme protein in the PCa cells as compared to their benign counterpart. This increase is even more pronounced in metastatic PCa tissues as compared to the PCa localized in the prostate. In the prostatectomy tissues from early-stage patients, the SSAT protein level is also high in the tissues obtained from the patients who ultimately progress to advanced metastatic disease. Based on these results combined with published data from our and other laboratories, we propose an activation of an autocrine feed-forward loop of PCa cell proliferation in the absence of androgen as a possible mechanism of castrate-resistant prostate cancer growth. © 2015 Wiley Periodicals, Inc.

  11. Human Papilloma Virus Detection by INNOLiPA HPV in Prostate Tissue from Men of Northeast Mexico

    PubMed

    Dávila-Rodríguez, Martha I; Ignacio Morales, Cesar V; Aragón Tovar, Anel R; Olache Jimenez, Delia; Castelán Maldonado, Edmundo; Lara Miranda, Sandra; Cortés Gutiérrez, Elva I

    2016-11-01

    Background: Prostatic adenocarcinoma by Prosate cancer (PCa) is the most prevalent cancer and the second cause of cancer-related death among men in the Western world. Human papilloma virus (HPV) may be considered as a preventable risk factor. In this study, we assessed the frequencies of HPV infection in prostatic adenocarcinoma and benign prostatic hyperplasia (BPH) cases in Northeast Mexico. Materials and Methods: A total of 87 paraffin-embedded blocks (from 25 and 62 patients with definite diagnoses of BPH and adenocarcinoma, respectively) were selected and subjected to INNOLiPA HPV Genotyping to detect 28 high- and low-risk HPV types. The rates of infection were compared in the two studied groups. Results: INNOLiPA HPV demonstrated great sensitivity for HPV detection on paraffin-embedded tissue. Global prevalence was 14.9% (13/87). HPV infection was positive in 19.4% (12/62) of patients with adenocarcinoma and 4.0% (1/25) of patients with BPH. HPV-11, which is considered to be low risk, was more prevalent. Interestingly, one patient with BPH and six with prostate cancer showed examples considered to be high risk (HPV-18, -51, -52, and -66). Conclusion: A higher rate of HPV infection among Mexican patients with prostatic carcinoma than among those with BPH was observed. HPV infections may thus contribute to the risk of prostate cancer. Further studies are required to elucidate any roles of HPV infection in prostate disease in Mexico and the effect of prevention and treatment of HPV infection on prostatic adenocarcinoma. Creative Commons Attribution License

  12. Human Papilloma Virus Detection by INNOLiPA HPV in Prostate Tissue from Men of Northeast Mexico

    PubMed Central

    Rodriguez, Martha I Dávila; Morales, Cesar V Ignacio; Tovar, Anel R Aragón; Jimenez, Delia Olache; Maldonado, Edmundo Castelán; Miranda, Sandra Lara; Gutiérrez, Elva I Cortés

    2016-01-01

    Background: Prostatic adenocarcinoma by Prosate cancer (PCa) is the most prevalent cancer and the second cause of cancer-related death among men in the Western world. Human papilloma virus (HPV) may be considered as a preventable risk factor. In this study, we assessed the frequencies of HPV infection in prostatic adenocarcinoma and benign prostatic hyperplasia (BPH) cases in Northeast Mexico. Materials and Methods: A total of 87 paraffin-embedded blocks (from 25 and 62 patients with definite diagnoses of BPH and adenocarcinoma, respectively) were selected and subjected to INNOLiPA HPV Genotyping to detect 28 high- and low-risk HPV types. The rates of infection were compared in the two studied groups. Results: INNOLiPA HPV demonstrated great sensitivity for HPV detection on paraffin-embedded tissue. Global prevalence was 14.9% (13/87). HPV infection was positive in 19.4% (12/62) of patients with adenocarcinoma and 4.0% (1/25) of patients with BPH. HPV-11, which is considered to be low risk, was more prevalent. Interestingly, one patient with BPH and six with prostate cancer showed examples considered to be high risk (HPV-18, -51, -52, and -66). Conclusion: A higher rate of HPV infection among Mexican patients with prostatic carcinoma than among those with BPH was observed. HPV infections may thus contribute to the risk of prostate cancer. Further studies are required to elucidate any roles of HPV infection in prostate disease in Mexico and the effect of prevention and treatment of HPV infection on prostatic adenocarcinoma. PMID:28030912

  13. Determination of doripenem penetration into human prostate tissue and assessment of dosing regimens for prostatitis based on site-specific pharmacokinetic-pharmacodynamic evaluation.

    PubMed

    Nakamura, Kogenta; Ikawa, Kazuro; Yamada, Yoshiaki; Arakawa, Maki; Zennami, Kenji; Nishikawa, Genya; Ikeda, Kayo; Morikawa, Norifumi; Honda, Nobuaki

    2012-02-01

    Prostatic hypertrophy patients prophylactically received a 0.5-hour infusion of doripenem (250 or 500 mg) before transurethral resection of the prostate. Doripenem concentrations in plasma and prostate tissue were measured chromatographically, and analysed pharmacokinetically using a three-compartment model. The approved doripenem regimens were assessed based on the time above the minimum inhibitory concentration for bacteria (T>MIC, % of 24 hours), an indicator for antibacterial effects, at the prostate. The prostate tissue/plasma ratios were 17.3% for the maximum drug concentration and 18.7% for the area under the drug concentration-time curve, and they were irrespective of the dose. Against Escherichia coli and Klebsiella species isolates, 500 mg once daily achieved a >90% probability of attaining the bacteriostatic target (20% T>MIC) in prostate tissue, and 500 mg twice daily achieved a >90% probability of attaining the bactericidal target (40% T>MIC) in prostate tissue.

  14. Isolation and genome-wide expression and methylation characterization of CD31+ cells from normal and malignant human prostate tissue

    PubMed Central

    Luo, Wei; Hu, Qiang; Wang, Dan; Deeb, Kristin K.; Ma, Yingyu; Morrison, Carl D.; Liu, Song; Johnson, Candace S.; Trump, Donald L.

    2013-01-01

    Endothelial cells (ECs) are an important component involved in the angiogenesis. Little is known about the global gene expression and epigenetic regulation in tumor endothelial cells. The identification of gene expression and epigenetic difference between human prostate tumor-derived endothelial cells (TdECs) and those in normal tissues may uncover unique biological features of TdEC and facilitate the discovery of new anti-angiogenic targets. We established a method for isolation of CD31+ endothelial cells from malignant and normal prostate tissues obtained at prostatectomy. TdECs and normal-derived ECs (NdECs) showed >90% enrichment in primary culture and demonstrated microvascular endothelial cell characteristics such as cobblestone morphology in monolayer culture, diI-acetyl-LDL uptake and capillary-tube like formation in Matrigel®. In vitro primary cultures of ECs maintained expression of endothelial markers such as CD31, von Willebrand factor, intercellular adhesion molecule, vascular endothelial growth factor receptor 1, and vascular endothelial growth factor receptor 2. We then conducted a pilot study of transcriptome and methylome analysis of TdECs and matched NdECs from patients with prostate cancer. We observed a wide spectrum of differences in gene expression and methylation patterns in endothelial cells, between malignant and normal prostate tissues. Array-based expression and methylation data were validated by qRT-PCR and bisulfite DNA pyrosequencing. Further analysis of transcriptome and methylome data revealed a number of differentially expressed genes with loci whose methylation change is accompanied by an inverse change in gene expression. Our study demonstrates the feasibility of isolation of ECs from histologically normal prostate and prostate cancer via CD31+ selection. The data, although preliminary, indicates that there exist widespread differences in methylation and transcription between TdECs and NdECs. Interestingly, only a small

  15. Cellular distribution of Glut-1 and Glut-5 in benign and malignant human prostate tissue.

    PubMed

    Reinicke, Karin; Sotomayor, Paula; Cisterna, Pedro; Delgado, Carolina; Nualart, Francisco; Godoy, Alejandro

    2012-02-01

    Over-expression of hexose transporters (Gluts), specifically Glut-1, is a common event in human malignancies. In prostate cancer (CaP), however, expression of Gluts has been characterized poorly. In this study, expression and distribution of Glut-1 and Glut-5 proteins were characterized using immunohistochemistry in 76 specimens of benign prostate, 10 specimens of high-grade intraepithelial neoplasia (HGPIN), and 28 specimens of CaP. In addition, mRNA expression of Glut-2, Glut-7, Glut-9, and Glut-11 was analyzed in a set of five specimens of benign prostate and CaP. In benign prostate, Glut-1 localized to the basal cells and to the basolateral membrane of secretory/luminal epithelial cells. Glut-5, however, localized to the apical membrane of secretory/luminal epithelial cells. In HGPIN, Glut-1 was immunohistochemically undetectable. Glut-5, however, localized to the apical membrane of the neoplastic epithelial cells. In CaP, Glut-1 and Glut-5, were immunohistochemically undetectable. However, over-expression of GLUT1 was observed in some specimens of highly proliferative intraductal CaP. Glut-7, Glut-9, and Glut-11 mRNAs were detected in benign prostate and CaP, however, only Glut-11 mRNA was consistently up-regulated in CaP compared to benign prostate. Low levels of expression of Glut-1 protein in the majority of CaP could explain, at least in part, the limited clinical applicability of positron emission tomography using 2-[18F]-fluoro-2-deoxy-D-glucose for imaging CaP. Moreover, expression of Glut-5 in HGPIN suggested that fructose could be utilized as potential metabolic substrate in HGPIN. Understanding the molecular mechanisms involved in regulation/dysregulation of Gluts in CaP could provide insight in the understanding of hexose metabolism in CaP.

  16. Monte Carlo modelling of angular radiance in tissue phantoms and human prostate: PDT light dosimetry.

    PubMed

    Barajas, O; Ballangrud, A M; Miller, G G; Moore, R B; Tulip, J

    1997-09-01

    Photodynamic therapy (PDT) is a promising technique for destroying tumours. Photosensitizing drugs presently available are not sufficiently tumour specific; hence, light dosimetry is required in order to control light exposure and thereby restrict cell kill to the target tissue to avoid damage to healthy tissue. Current light dosimetry methods rely on tissue optical characterization by fluence measurements at several points. Fluence-based tissue characterization is impractical for tumours in organs such as prostate where access by optical probes is limited and the tumours are highly optically inhomogeneous. This paper explores the potential of radiance-based light dosimetry as an alternative. Correlation is found between Monte Carlo simulation of radiance in a tissue phantom and radiance measurements made using a new radiance probe. Radiance is sensitive to variations in the tissue optical parameters, absorption coefficient mu(a), scattering coefficient mu(s), and anisotropy factor g, and therefore is potentially useful for tissue characterization. Radiance measurements have several advantages over fluence measurements. Radiance measurements provide more information from a single location, better spatial resolution of the tissue optical parameters, and higher sensitivity in discriminating between different media. However, the Monte Carlo method is too slow to be of practical value for tissue characterization by correlation of measured and simulated radiance. An analytical solution to the transport equation for radiance would be desirable as this would facilitate and increase the speed of tissue characterization.

  17. Characterization of adenoviral transduction profile in prostate cancer cells and normal prostate tissue.

    PubMed

    Ai, Jianzhong; Tai, Phillip W L; Lu, Yi; Li, Jia; Ma, Hong; Su, Qin; Wei, Qiang; Li, Hong; Gao, Guangping

    2017-09-01

    Prostate diseases are common in males worldwide with high morbidity. Gene therapy is an attractive therapeutic strategy for prostate diseases, however, it is currently underdeveloped. As well known, adeno virus (Ad) is the most widely used gene therapy vector. The aims of this study are to explore transduction efficiency of Ad in prostate cancer cells and normal prostate tissue, thus further providing guidance for future prostate pathophysiological studies and therapeutic development of prostate diseases. We produced Ad expressing enhanced green fluorescence protein (EGFP), and characterized the transduction efficiency of Ad in both human and mouse prostate cancer cell lines in vitro, as well as prostate tumor xenograft, and wild-type mouse prostate tissue in vivo. Ad transduction efficiency was determined by EGFP fluorescence using microscopy and flow cytometry. Cell type-specific transduction was examined by immunofluorescence staining of cell markers. Our data showed that Ad efficiently transduced human and mouse prostate cancer cells in vitro in a dose dependent manner. Following intratumoral and intraprostate injection, Ad could efficiently transduce prostate tumor xenograft and the major prostatic cell types in vivo, respectively. Our findings suggest that Ad can efficiently transduce prostate tumor cells in vitro as well as xenograft and normal prostate tissue in vivo, and further indicate that Ad could be a potentially powerful toolbox for future gene therapy of prostate diseases. © 2017 Wiley Periodicals, Inc.

  18. Gene Expression in Single Cells Isolated from the CWR-R1 Prostate Cancer Cell Line and Human Prostate Tissue Based on the Side Population Phenotype

    PubMed Central

    Gangavarapu, Kalyan J; Miller, Austin; Huss, Wendy J

    2016-01-01

    Defining biological signals at the single cell level can identify cancer initiating driver mutations. Techniques to isolate single cells such as microfluidics sorting and magnetic capturing systems have limitations such as: high cost, labor intense, and the requirement of a large number of cells. Therefore, the goal of our current study is to identify a cost and labor effective, reliable, and reproducible technique that allows single cell isolation for analysis to promote regular laboratory use, including standard reverse transcription PCR (RT-PCR). In the current study, we utilized single prostate cells isolated from the CWR-R1 prostate cancer cell line and human prostate clinical specimens, based on the ATP binding cassette (ABC) transporter efflux of dye cycle violet (DCV), side population assay. Expression of four genes: ABCG2; Aldehyde dehydrogenase1A1 (ALDH1A1); androgen receptor (AR); and embryonic stem cell marker, Oct-4, were determined. Results from the current study in the CWR-R1 cell line showed ABCG2 and ALDH1A1 gene expression in 67% of single side population cells and in 17% or 100% of non-side population cells respectively. Studies using single cells isolated from clinical specimens showed that the Oct-4 gene is detected in only 22% of single side population cells and in 78% of single non-side population cells. Whereas, AR gene expression is in 100% single side population and non-side population cells isolated from the same human prostate clinical specimen. These studies show that performing RT-PCR on single cells isolated by FACS can be successfully conducted to determine gene expression in single cells from cell lines and enzymatically digested tissue. While these studies provide a simple yes/no expression readout, the more sensitive quantitative RT-PCR would be able to provide even more information if necessary. PMID:27785389

  19. Changes of collagen and nicotinamide adenine dinucleotide in human cancerous and normal prostate tissues studied using native fluorescence spectroscopy with selective excitation wavelength

    NASA Astrophysics Data System (ADS)

    Pu, Yang; Wang, Wubao; Tang, Guichen; Alfano, Robert R.

    2010-07-01

    The fluorescence spectra of human cancerous and normal prostate tissues obtained by the selective excitation wavelength of 340 nm were measured. The contributions of principle biochemical components to tissue fluorescence spectra were investigated using the method of multivariate curve resolution with alternating least squares. The results show that there is a reduced contribution from the emission of collagen and increased contribution from nicotinamide adenine dinucleotide (NADH) in cancerous tissues as compared with normal tissue. This difference is attributed to the changes of relative contents of NADH and collagen during cancer development. This research may present a potential native biomarker for prostate cancer detection.

  20. Proteomic Upregulation of Fatty Acid Synthase and Fatty Acid Binding Protein 5 and Identification of Cancer- and Race-Specific Pathway Associations in Human Prostate Cancer Tissues

    PubMed Central

    Myers, Jennifer S.; von Lersner, Ariana K.; Sang, Qing-Xiang Amy

    2016-01-01

    Protein profiling studies of prostate cancer have been widely used to characterize molecular differences between diseased and non-diseased tissues. When combined with pathway analysis, profiling approaches are able to identify molecular mechanisms of prostate cancer, group patients by cancer subtype, and predict prognosis. This strategy can also be implemented to study prostate cancer in very specific populations, such as African Americans who have higher rates of prostate cancer incidence and mortality than other racial groups in the United States. In this study, age-, stage-, and Gleason score-matched prostate tumor specimen from African American and Caucasian American men, along with non-malignant adjacent prostate tissue from these same patients, were compared. Protein expression changes and altered pathway associations were identified in prostate cancer generally and in African American prostate cancer specifically. In comparing tumor to non-malignant samples, 45 proteins were significantly cancer-associated and 3 proteins were significantly downregulated in tumor samples. Notably, fatty acid synthase (FASN) and epidermal fatty acid-binding protein (FABP5) were upregulated in human prostate cancer tissues, consistent with their known functions in prostate cancer progression. Aldehyde dehydrogenase family 1 member A3 (ALDH1A3) was also upregulated in tumor samples. The Metastasis Associated Protein 3 (MTA3) pathway was significantly enriched in tumor samples compared to non-malignant samples. While the current experiment was unable to detect statistically significant differences in protein expression between African American and Caucasian American samples, differences in overrepresentation and pathway enrichment were found. Structural components (Cytoskeletal Proteins and Extracellular Matrix Protein protein classes, and Biological Adhesion Gene Ontology (GO) annotation) were overrepresented in African American but not Caucasian American tumors. Additionally, 5

  1. Fluconazole penetration into the human prostate.

    PubMed Central

    Finley, R W; Cleary, J D; Goolsby, J; Chapman, S W

    1995-01-01

    Fluconazole concentrations in the serum and prostate of human volunteers undergoing transurethral resection for benign prostatic hypertrophy were measured. There was a high correlation (r = 0.783) between serum (mean = 6.6 micrograms/ml) and tissue (mean = 1.9 micrograms/g) fluconazole concentrations, and these data were used to construct a model for local tissue concentrations. PMID:7726532

  2. Apparent diffusion coefficient and sodium concentration measurements in human prostate tissue via hydrogen-1 and sodium-23 magnetic resonance imaging in a clinical setting at 3T.

    PubMed

    Hausmann, Daniel; Konstandin, Simon; Wetterling, Friedrich; Haneder, Stefan; Nagel, Armin M; Dinter, Dietmar J; Schönberg, Stefan O; Zöllner, Frank G; Schad, Lothar R

    2012-12-01

    Multiparametric magnetic resonance imaging (MRI) of the prostate involves morphologic and functional imaging techniques, which could potentially enable to distinguish between common benign prostate diseases, especially prostatitis and prostate cancer. The aim of this study was to determine the apparent diffusion coefficient (ADC) and the tissue sodium concentration (TSC) in 2 different regions of the human prostate, that is, the central gland (CG) and the peripheral gland (PG), by means of standard hydrogen-1 (H) MRI and quantitative sodium-23 (Na) MRI at 3 T to increase the spectrum of diagnostic parameters for prostate examinations. All measurements were performed on a 3-T clinical whole-body magnetic resonance (MR) scanner. Na MR images were acquired with density-adapted 3-dimensional radial sequence and isotropic voxel resolution of 5 × 5 × 5 mm. After approval by the institutional review board and informed consent were obtained, 8 healthy volunteers were included in this study. Diffusion-weighted imaging and T2-weighted images were also recorded and hence enabled the correlation of measured TSC values with current state-of-the-art H MRI techniques. The ADC in both subregions was measured to be at normal levels (CG, 1.19 [0.09] ×10 mm/s; PG, 1.54 [0.14] × 10 mm/s) in all 8 volunteers. Good spatial resolution of the Na images allowed for an easy identification of the same subregions from the Na MR images. In healthy adult volunteers (age, 29 [2] years), the TSC was measured lower in central (55 [15] mmol/L) and higher in peripheral (69 [16] mmol/L) prostate tissue. A correlation between the TSC and the ADC in the 2 subregions was found in the same volunteer group (Pearson correlation coefficient = 0.87). For the first time, TSC was spatially resolved in human prostate tissue by means of Na MRI. Interestingly, the herein found TSC values of ∼60 mmol/L were half as high as in a previously reported Na MRI study where prostate TSC was measured in 5-month

  3. Ultra-high performance liquid chromatographic determination of levofloxacin in human plasma and prostate tissue with use of experimental design optimization procedures.

    PubMed

    Szerkus, O; Jacyna, J; Wiczling, P; Gibas, A; Sieczkowski, M; Siluk, D; Matuszewski, M; Kaliszan, R; Markuszewski, M J

    2016-09-01

    Fluoroquinolones are considered as gold standard for the prevention of bacterial infections after transrectal ultrasound guided prostate biopsy. However, recent studies reported that fluoroquinolone- resistant bacterial strains are responsible for gradually increasing number of infections after transrectal prostate biopsy. In daily clinical practice, antibacterial efficacy is evaluated only in vitro, by measuring the reaction of bacteria with an antimicrobial agent in culture media (i.e. calculation of minimal inhibitory concentration). Such approach, however, has no relation to the treated tissue characteristics and might be highly misleading. Thus, the objective of this study was to develop, with the use of Design of Experiments approach, a reliable, specific and sensitive ultra-high performance liquid chromatography- diode array detection method for the quantitative analysis of levofloxacin in plasma and prostate tissue samples obtained from patients undergoing prostate biopsy. Moreover, correlation study between concentrations observed in plasma samples vs prostatic tissue samples was performed, resulting in better understanding, evaluation and optimization of the fluoroquinolone-based antimicrobial prophylaxis during transrectal ultrasound guided prostate biopsy. Box-Behnken design was employed to optimize chromatographic conditions of the isocratic elution program in order to obtain desirable retention time, peak symmetry and resolution of levofloxacine and ciprofloxacine (internal standard) peaks. Fractional Factorial design 2(4-1) with four center points was used for screening of significant factors affecting levofloxacin extraction from the prostatic tissue. Due to the limited number of tissue samples the prostatic sample preparation procedure was further optimized using Central Composite design. Design of Experiments approach was also utilized for evaluation of parameter robustness. The method was found linear over the range of 0.030-10μg/mL for human

  4. A biospectroscopic analysis of human prostate tissue obtained from different time periods points to a trans-generational alteration in spectral phenotype

    PubMed Central

    Theophilou, Georgios; Lima, Kássio M. G.; Briggs, Matthew; Martin-Hirsch, Pierre L.; Stringfellow, Helen F.; Martin, Francis L.

    2015-01-01

    Prostate cancer is the most commonly-diagnosed malignancy in males worldwide; however, there is marked geographic variation in incidence that may be associated with a Westernised lifestyle. We set out to determine whether attenuated total reflection Fourier-transform infrared (ATR-FTIR) or Raman spectroscopy combined with principal component analysis-linear discriminant analysis or variable selection techniques employing genetic algorithm or successive projection algorithm could be utilised to explore differences between prostate tissues from differing years. In total, 156 prostate tissues from transurethral resection of the prostate procedures for benign prostatic hyperplasia from 1983 to 2013 were collected. These were distributed to form seven categories: 1983–1984 (n = 20), 1988–1989 (n = 25), 1993–1994 (n = 21), 1998–1999 (n = 21), 2003–2004 (n = 21), 2008–2009 (n = 20) and 2012–2013 (n = 21). Ten-μm-thick tissue sections were floated onto Low-E (IR-reflective) slides for ATR-FTIR or Raman spectroscopy. The prostate tissue spectral phenotype altered in a temporal fashion. Examination of the two categories that are at least one generation (30 years) apart indicated highly-significant segregation, especially in spectral regions containing DNA and RNA bands (≈1,000–1,490 cm−1). This may point towards alterations that have occurred through genotoxicity or through epigenetic modifications. Immunohistochemical studies for global DNA methylation supported this. This study points to a trans-generational phenotypic change in human prostate. PMID:26310632

  5. A biospectroscopic analysis of human prostate tissue obtained from different time periods points to a trans-generational alteration in spectral phenotype.

    PubMed

    Theophilou, Georgios; Lima, Kássio M G; Briggs, Matthew; Martin-Hirsch, Pierre L; Stringfellow, Helen F; Martin, Francis L

    2015-08-27

    Prostate cancer is the most commonly-diagnosed malignancy in males worldwide; however, there is marked geographic variation in incidence that may be associated with a Westernised lifestyle. We set out to determine whether attenuated total reflection Fourier-transform infrared (ATR-FTIR) or Raman spectroscopy combined with principal component analysis-linear discriminant analysis or variable selection techniques employing genetic algorithm or successive projection algorithm could be utilised to explore differences between prostate tissues from differing years. In total, 156 prostate tissues from transurethral resection of the prostate procedures for benign prostatic hyperplasia from 1983 to 2013 were collected. These were distributed to form seven categories: 1983-1984 (n = 20), 1988-1989 (n = 25), 1993-1994 (n = 21), 1998-1999 (n = 21), 2003-2004 (n = 21), 2008-2009 (n = 20) and 2012-2013 (n = 21). Ten-μm-thick tissue sections were floated onto Low-E (IR-reflective) slides for ATR-FTIR or Raman spectroscopy. The prostate tissue spectral phenotype altered in a temporal fashion. Examination of the two categories that are at least one generation (30 years) apart indicated highly-significant segregation, especially in spectral regions containing DNA and RNA bands (≈1,000-1,490 cm(-1)). This may point towards alterations that have occurred through genotoxicity or through epigenetic modifications. Immunohistochemical studies for global DNA methylation supported this. This study points to a trans-generational phenotypic change in human prostate.

  6. Differential expression of metallothioneins (MTs) 1, 2, and 3 in response to zinc treatment in human prostate normal and malignant cells and tissues

    PubMed Central

    Wei, Hua; Desouki, Mohamed Mokhtar; Lin, Shufei; Xiao, Dakai; Franklin, Renty B; Feng, Pei

    2008-01-01

    Background The disturbance of zinc homeostasis featured with a significant decrease of cellular zinc level was well documented to associate with the development and progression of human prostate malignancy. We have previously reported that zinc treatment induces prostate malignant cell apoptosis through mitochondrial pathway. Metallothionein (MT) is a major receptor/donor of zinc in the cells. However, the studies on the expression of MT in association with the prostate pathological and malignant status are very limited, and the zinc regulation of MT isoform expression in prostate cells remains elusive. The goals of this study were to define the expression of endogenous MTs, the isoforms of MT 1, 2, 3 at both messenger ribonucleic acid (mRNA) and protein levels; and to investigate the zinc effect on MT expression in normal prostate, benign prostatic hyperplasia (BPH) and malignant PC-3 cells, and in relevant human tissues. Cellular MT proteins were detected by immunohistochemistry, fluorescence staining and Western blot analysis; reverse transcription polymerase chain reaction (RT-PCR) was used to determine the MT isoform-specific mRNAs. Results Our results demonstrated a significant suppression of endogenous levels of MT1/2 in malignant PC-3 cells (95% reduction compared to the normal prostate cells) and in human adenocarcinoma tissues (73% MT1/2 negative). A moderate reduction of MT1/2 expression was observed in BPH. Zinc treatment remarkably induced MT1/2 expression in PC-3 and BPH cells, which was accordant with the restored cellular zinc level. MT 3, as a growth inhibitory factor, was detected and up-regulated by zinc mainly in BPH cells. Conclusion This study provided evidence of the association of attenuated MT1/2 with prostate tumor progression, and the zinc induction of MT1/2 expression resulting in cellular zinc restoration. The results suggest the potential of MT1/2 as a candidate biomarker for prostate cancer and the utilization of zinc in prostate

  7. Evaluation of discoidin domain receptor-2 (DDR2) expression level in normal, benign, and malignant human prostate tissues.

    PubMed

    Azemikhah, Mitra; Ashtiani, Hamidreza Ahmadi; Aghaei, Mahmoud; Rastegar, Hosein

    2015-01-01

    Discoidin domain receptor (DDR) is a new member of the receptor tyrosine kinase family. There are two isoforms of discoidin domain receptor (DDR), DDR1 and DDR2. These receptors play a major role in the adhesion, motility and cell proliferation. Due to the important role of DDR2 in the development of tumor extension, this receptor is pivotal in the field of carcinogenesis. The aim of this study was to investigate the mRNA and protein expression of DDR2, in the malignant, benign prostatic hyperplasia (BPH) and normal tissues of patients with prostate cancer. In this study the gene and protein expression of DDR2 in adjacent normal (n=40), BPH (n=40), and malignant (n=40) prostate tissue were measured using real-time PCR and Western blotting. Then, the correlation of DDR2 gene and protein expression with prognostic factors such as age, tumor grade, tumor stage, lymph node involvement, and serum prostate-specific antigen (PSA) concentration were evaluated. The relative mRNA and protein expression level of DDR2 in malignant and benign prostate tissue was significantly higher than those of adjacent normal tissues (P<0.01). This expression was found to increase approximately 3.5 and 2.1 fold for mRNA and protein levels, respectively. Spearman test indicated a significant correlation between DDR2 mRNA and protein expression with prognostic factors such as tumor grade, stage, lymph node involvement, and serum PSA concentration. However, significant correlation with age was not observed. These findings suggest that DDR2 is a cancer-related gene associated with the aggressive progression of prostate cancer patients.

  8. Tissue elasticity properties as biomarkers for prostate cancer.

    PubMed

    Hoyt, Kenneth; Castaneda, Benjamin; Zhang, Man; Nigwekar, Priya; di Sant'agnese, P Anthony; Joseph, Jean V; Strang, John; Rubens, Deborah J; Parker, Kevin J

    2008-01-01

    In this paper we evaluate tissue elasticity as a longstanding but qualitative biomarker for prostate cancer and sonoelastography as an emerging imaging tool for providing qualitative and quantitative measurements of prostate tissue stiffness. A Kelvin-Voigt Fractional Derivative (KVFD) viscoelastic model was used to characterize mechanical stress relaxation data measured from human prostate tissue samples. Mechanical testing results revealed that the viscosity parameter for cancerous prostate tissue is greater than that derived from normal tissue by a factor of approximately 2.4. It was also determined that a significant difference exists between normal and cancerous prostate tissue stiffness (p < 0.01) yielding an average elastic contrast that increases from 2.1 at 0.1 Hz to 2.5 at 150 Hz. Qualitative sonoelastographic results show promise for cancer detection in prostate and may prove to be an effective adjunct imaging technique for biopsy guidance. Elasticity images obtained with quantitative sonoelastography agree with mechanical testing and histological results. Overall, results indicate tissue elasticity is a promising biomarker for prostate cancer.

  9. Expression of prostate-specific antigen (PSA) and human glandular kallikrein 2 (hK2) in ileum and other extraprostatic tissues.

    PubMed

    Olsson, A Yvonne; Bjartell, Anders; Lilja, Hans; Lundwall, Ake

    2005-01-10

    Prostate-specific antigen (PSA) is a widely used marker for prostate cancer. In the literature, there are reports of nonprostatic expression of PSA that potentially can affect early diagnosis. However, the results are scattered and inconclusive, which motivated us to conduct a more comprehensive study of the tissue distribution of PSA and the closely related protein human glandular kallikrein 2 (hK2). RT-PCR, in situ hybridization and immunohistochemistry were used to detect expression of both PSA and hK2 in secretory epithelial cells of trachea, thyroid gland, mammary gland, salivary gland, jejunum, ileum, epididymis, seminal vesicle and urethra, as well as in Leydig cells, pancreatic exocrine glands and epidermis. Immunometric measurements revealed that the concentration of PSA in nonprostatic tissues represents less than 1% of the amount in normal prostate. Pronounced expression of PSA was detected in the Paneth cells in ileum, which prompted us to compare functional parameters of PSA in ileum and prostate. We found that in homogenates from these 2 tissues, PSA manifested equivalent amidolytic activity and capacity to form complexes with protease inhibitors in blood in vitro. Thus, PSA released from sources other than the prostate may add to the plasma pool of this protein, but given the lower levels detected from those sites, it is unlikely that nonprostatic PSA normally can interfere with the diagnosis of prostate cancer. Nevertheless, this risk should not be neglected as it may be of clinical significance under certain circumstances. Supplementary material for this article can be found on the International Journal of Cancer website at http://www.interscience.wiley.com/jpages/0020-7136/suppmat/index.html.

  10. Stokes polarimetry imaging of dog prostate tissue

    NASA Astrophysics Data System (ADS)

    Kim, Jihoon; Johnston, William K., III; Walsh, Joseph T., Jr.

    2010-02-01

    Prostate cancer is the second leading cause of death in the United States in 2009. Radical prostatectomy (complete removal of the prostate) is the most common treatment for prostate cancer, however, differentiating prostate tissue from adjacent bladder, nerves, and muscle is difficult. Improved visualization could improve oncologic outcomes and decrease damage to adjacent nerves and muscle important for preservation of potency and continence. A novel Stokes polarimetry imaging (SPI) system was developed and evaluated using a dog prostate specimen in order to examine the feasibility of the system to differentiate prostate from bladder. The degree of linear polarization (DOLP) image maps from linearly polarized light illumination at different visible wavelengths (475, 510, and 650 nm) were constructed. The SPI system used the polarization property of the prostate tissue. The DOLP images allowed advanced differentiation by distinguishing glandular tissue of prostate from the muscular-stromal tissue in the bladder. The DOLP image at 650 nm effectively differentiated prostate and bladder by strong DOLP in bladder. SPI system has the potential to improve surgical outcomes in open or robotic-assisted laparoscopic removal of the prostate. Further in vivo testing is warranted.

  11. Quantification of Protein Signatures in Archived Human Prostate Tissues Using Shotgun Proteomic Methods

    DTIC Science & Technology

    2012-05-01

    Fig. 2). The detergent-solubilized proteins were subsequently incubated with wheat - germ agglutinin (WGA) and concanavalin-A (ConA) beads, washed...optimizing protocols to extract and profile proteins in matched normal and diseased tissue samples using directed mass spectrometry methods. The ultimate...able to extract up to 100 micrograms of total protein using whole- mount FFPE RP tissue block samples. This Figure 2. Silver-stained SDS-PAGE gel

  12. Examination of CK2α and NF-κB p65 expression in human benign prostatic hyperplasia and prostate cancer tissues.

    PubMed

    Qaiser, Fatima; Trembley, Janeen H; Sadiq, Sarah; Muhammad, Iqbal; Younis, Rubina; Hashmi, Shoaib Naiyar; Murtaza, Badar; Rector, Thomas S; Naveed, Abdul Khaliq; Ahmed, Khalil

    2016-09-01

    Protein kinase CK2 plays a critical role in cell growth, proliferation, and suppression of cell death. CK2 is overexpressed, especially in the nuclear compartment, in the majority of cancers, including prostate cancer (PCa). CK2-mediated activation of transcription factor nuclear factor kappa B (NF-κB) p65 is a key step in cellular proliferation, resulting in translocation of NF-κB p65 from the cytoplasm to the nucleus. As CK2 expression and activity are also elevated in benign prostatic hyperplasia (BPH), we sought to increase the knowledge of CK2 function in benign and malignant prostate by examination of the relationships between nuclear CK2 and nuclear NF-κB p65 protein expression. The expression level and localization of CK2α and NF-κB p65 proteins in PCa and BPH tissue specimens was determined. Nuclear CK2α and NF-κB p65 protein levels are significantly higher in PCa compared with BPH, and these proteins are positively correlated with each other in both diseases. Nuclear NF-κB p65 levels correlated with Ki-67 or with cytoplasmic NF-κB p65 expression in BPH, but not in PCa. The findings provide information that combined analysis of CK2α and NF-κB p65 expression in prostate specimens relates to the disease status. Increased nuclear NF-κB p65 expression levels in PCa specifically related to nuclear CK2α levels, indicating a possible CK2-dependent relationship in malignancy. In contrast, nuclear NF-κB p65 protein levels related to both Ki-67 and cytoplasmic NF-κB p65 levels exclusively in BPH, suggesting a potential separate impact for NF-κB p65 function in proliferation for benign disease as opposed to malignant disease.

  13. Genome-wide DNA methylation measurements in prostate tissues uncovers novel prostate cancer diagnostic biomarkers and transcription factor binding patterns.

    PubMed

    Kirby, Marie K; Ramaker, Ryne C; Roberts, Brian S; Lasseigne, Brittany N; Gunther, David S; Burwell, Todd C; Davis, Nicholas S; Gulzar, Zulfiqar G; Absher, Devin M; Cooper, Sara J; Brooks, James D; Myers, Richard M

    2017-04-17

    Current diagnostic tools for prostate cancer lack specificity and sensitivity for detecting very early lesions. DNA methylation is a stable genomic modification that is detectable in peripheral patient fluids such as urine and blood plasma that could serve as a non-invasive diagnostic biomarker for prostate cancer. We measured genome-wide DNA methylation patterns in 73 clinically annotated fresh-frozen prostate cancers and 63 benign-adjacent prostate tissues using the Illumina Infinium HumanMethylation450 BeadChip array. We overlaid the most significantly differentially methylated sites in the genome with transcription factor binding sites measured by the Encyclopedia of DNA Elements consortium. We used logistic regression and receiver operating characteristic curves to assess the performance of candidate diagnostic models. We identified methylation patterns that have a high predictive power for distinguishing malignant prostate tissue from benign-adjacent prostate tissue, and these methylation signatures were validated using data from The Cancer Genome Atlas Project. Furthermore, by overlaying ENCODE transcription factor binding data, we observed an enrichment of enhancer of zeste homolog 2 binding in gene regulatory regions with higher DNA methylation in malignant prostate tissues. DNA methylation patterns are greatly altered in prostate cancer tissue in comparison to benign-adjacent tissue. We have discovered patterns of DNA methylation marks that can distinguish prostate cancers with high specificity and sensitivity in multiple patient tissue cohorts, and we have identified transcription factors binding in these differentially methylated regions that may play important roles in prostate cancer development.

  14. Isolation and analysis of discreet human prostate cellular populations

    PubMed Central

    Strand, Douglas W.; Aaron, LaTayia; Henry, Gervaise; Franco, Omar E.; Hayward, Simon W.

    2015-01-01

    The use of lineage tracing in transgenic mouse models has revealed an abundance of subcellular phenotypes responsible for maintaining prostate homeostasis. The ability to use fresh human tissues to examine the hypotheses generated by these mouse experiments has been greatly enhanced by technical advances in tissue processing, flow cytometry and cell culture. We describe in detail the optimization of protocols for each of these areas to facilitate research on solving human prostate diseases through the analysis of human tissue. PMID:26546040

  15. Acoustic Radiation Force Impulse Imaging of Human Prostates ex vivo

    PubMed Central

    Zhai, Liang; Madden, John; Foo, Wen-Chi; Palmeri, Mark L.; Mouraviev, Vladimir; Polascik, Thomas J.; Nightingale, Kathryn R.

    2010-01-01

    It has been challenging for clinicians using current imaging modalities to visualize internal structures and detect lesions inside human prostates. Lack of contrast among prostatic tissues and high false positive or negative detection rates of prostate lesions have limited the use of current imaging modalities in the diagnosis of prostate cancer. In this study, Acoustic Radiation Force Impulse (ARFI) imaging is introduced to visualize the anatomic and abnormal structures in freshly excised human prostates. A modified Siemens Antares™ ultrasound scanner and a Siemens VF10-5 linear array were used to acquire ARFI images. The transducer was attached to a three-dimensional (3D) translation stage, which was programmed to automate volumetric data acquisition. A depth dependent gain (DDG) method was developed and applied to 3D ARFI datasets to compensate for the displacement gradients associated with spatially varying radiation force magnitudes as a function of depth. Nine human prostate specimens were collected and imaged immediately after surgical excision. Prostate anatomical structures such as seminal vesicles, ejaculatory ducts, peripheral zone, central zone, transition zone and verumontanum were visualized with high spatial resolution and in good agreement with McNeal's zonal anatomy. The characteristic appearance of prostate pathologies, such as prostate cancerous lesions, benign prostatic hyperplasia, calcified tissues and atrophy were identified in ARFI images based upon correlation with the corresponding histological slides. This study demonstrates that ARFI imaging can be used to visualize internal structures and detecting suspicious lesions in the prostate and appears promising for image guidance of prostate biopsy. PMID:20350685

  16. HUMAN PROSTATE CANCER RISK FACTORS

    EPA Science Inventory

    Prostate cancer has the highest prevalence of any non-skin cancer in the human body, with similar likelihood of neoplastic foci found within the prostates of men around the world regardless of diet, occupation, lifestyle, or other factors. Essentially all men with circulating an...

  17. HUMAN PROSTATE CANCER RISK FACTORS

    EPA Science Inventory

    Prostate cancer has the highest prevalence of any non-skin cancer in the human body, with similar likelihood of neoplastic foci found within the prostates of men around the world regardless of diet, occupation, lifestyle, or other factors. Essentially all men with circulating an...

  18. The histology of prostate tissue following prostatic artery embolization for the treatment of benign prostatic hyperplasia.

    PubMed

    Camara-Lopes, George; Mattedi, Romulo; Antunes, Alberto A; Carnevale, Francisco C; Cerri, Giovanni G; Srougi, Miguel; Alves, Venancio A; Leite, Katia R M

    2013-01-01

    Prostatic artery embolization (PAE) for the treatment of patients with symptomatic benign prostatic hyperplasia (BPH) is believed to be a safe procedure with a low risk of adverse side effects. Artery embolization is a viable treatment option in patients who are refractory to the classic noninvasive treatments. Knowledge of the histological characteristics of prostate tissue following the procedure is still limited. In this study, we describe the microscopic aspects of the prostate following PAE for BPH. Two patients underwent transurethral resections of the prostate (TURP) after PAE. Embolizations were performed under local anesthesia with an initial pelvic angiography to evaluate the iliac vessels and the prostate arteries using a 2.8 French microcatheter. The prostate was embolized with 300-500 µm Microspheres (Embosphere ®), using complete blood stasis as the end point. The prostate tissues were analyzed histologically to characterize the effects of the embolization. The embolic material within the prostate tissue was easily identified as homogeneous, bright eosin-red spheroids filling the vessel lumens. Ischemic necrosis surrounded or not by chronic inflammatory reactions containing macrophages were considered as a result of the artery embolization. Also, some aspects related to the healing process were observed being fibrotic nodules surrounded by glands with squamous metaplasia of the epithelial lining the most important. In the remaining sections, due to the precocious surgical intervention, the classic findings of BPH were still present with the glandular and stromal hyperplasia associated with nonspecific chronic prostatitis. This is the first description of prostate histology in BPH patients treated by PAE, a new procedure that is being used increasingly as a therapeutic intervention. The recognition of the changes caused by this new modality of treatment has become a very important differential in a chronic granulomatous reaction of the prostate

  19. Human Prostate Cancer Hallmarks Map.

    PubMed

    Datta, Dipamoy; Aftabuddin, Md; Gupta, Dinesh Kumar; Raha, Sanghamitra; Sen, Prosenjit

    2016-08-01

    Human prostate cancer is a complex heterogeneous disease that mainly affects elder male population of the western world with a high rate of mortality. Acquisitions of diverse sets of hallmark capabilities along with an aberrant functioning of androgen receptor signaling are the central driving forces behind prostatic tumorigenesis and its transition into metastatic castration resistant disease. These hallmark capabilities arise due to an intense orchestration of several crucial factors, including deregulation of vital cell physiological processes, inactivation of tumor suppressive activity and disruption of prostate gland specific cellular homeostasis. The molecular complexity and redundancy of oncoproteins signaling in prostate cancer demands for concurrent inhibition of multiple hallmark associated pathways. By an extensive manual curation of the published biomedical literature, we have developed Human Prostate Cancer Hallmarks Map (HPCHM), an onco-functional atlas of human prostate cancer associated signaling and events. It explores molecular architecture of prostate cancer signaling at various levels, namely key protein components, molecular connectivity map, oncogenic signaling pathway map, pathway based functional connectivity map etc. Here, we briefly represent the systems level understanding of the molecular mechanisms associated with prostate tumorigenesis by considering each and individual molecular and cell biological events of this disease process.

  20. Expression of a Human Prostatic Acid Phosphatase (PAP)-IgM Fc Fusion Protein in Plants Using In vitro Tissue Subculture.

    PubMed

    Kang, Yang J; Kim, Deuk-Su; Myung, Soon-Chul; Ko, Kisung

    2017-01-01

    In this study, prostatic acid phosphatase (PAP), which is overexpressed in human prostate cancer cells, was cloned to be fused to the IgM constant fragment (Fc) for enhancing immunogenicity and expressed in transgenic tobacco plants. Then, the transgenic plants were propagated by in vitro tissue subculture. Gene insertion and expression of the recombinant PAP-IgM Fc fusion protein were confirmed in each tested the first, second, and third subculture generations (SG1, SG2, and SG3, respectively). Transcription levels were constantly maintained in the SG1, SG2, and SG3 leaf section (top, middle, and base). The presence of the PAP-IgM Fc gene was also confirmed in each leaf section in all tested subculture generations. RNA expression was confirmed in all subculture generations using real-time PCR and quantitative real-time PCR. PAP-IgM Fc protein expression was confirmed in all leaves of the SG1, SG2, and SG3 recombinant transgenic plants by using quantitative western blotting and chemiluminescence immunoassays. These results demonstrate that the recombinant protein was stably expressed for several generations of in vitro subculture. Therefore, transgenic plants can be propagated using in vitro tissue subculture for the production of recombinant proteins.

  1. Expression of a Human Prostatic Acid Phosphatase (PAP)-IgM Fc Fusion Protein in Plants Using In vitro Tissue Subculture

    PubMed Central

    Kang, Yang J.; Kim, Deuk-Su; Myung, Soon-Chul; Ko, Kisung

    2017-01-01

    In this study, prostatic acid phosphatase (PAP), which is overexpressed in human prostate cancer cells, was cloned to be fused to the IgM constant fragment (Fc) for enhancing immunogenicity and expressed in transgenic tobacco plants. Then, the transgenic plants were propagated by in vitro tissue subculture. Gene insertion and expression of the recombinant PAP-IgM Fc fusion protein were confirmed in each tested the first, second, and third subculture generations (SG1, SG2, and SG3, respectively). Transcription levels were constantly maintained in the SG1, SG2, and SG3 leaf section (top, middle, and base). The presence of the PAP-IgM Fc gene was also confirmed in each leaf section in all tested subculture generations. RNA expression was confirmed in all subculture generations using real-time PCR and quantitative real-time PCR. PAP-IgM Fc protein expression was confirmed in all leaves of the SG1, SG2, and SG3 recombinant transgenic plants by using quantitative western blotting and chemiluminescence immunoassays. These results demonstrate that the recombinant protein was stably expressed for several generations of in vitro subculture. Therefore, transgenic plants can be propagated using in vitro tissue subculture for the production of recombinant proteins. PMID:28293250

  2. Quantitative analysis of BTF3, HINT1, NDRG1 and ODC1 protein over-expression in human prostate cancer tissue.

    PubMed

    Symes, Andrew J; Eilertsen, Marte; Millar, Michael; Nariculam, Joseph; Freeman, Alex; Notara, Maria; Feneley, Mark R; Patel, Hitendra R H; Patel, Hitenedra R H; Masters, John R W; Ahmed, Aamir

    2013-01-01

    Prostate carcinoma is the most common cancer in men with few, quantifiable, biomarkers. Prostate cancer biomarker discovery has been hampered due to subjective analysis of protein expression in tissue sections. An unbiased, quantitative immunohistochemical approach provided here, for the diagnosis and stratification of prostate cancer could overcome this problem. Antibodies against four proteins BTF3, HINT1, NDRG1 and ODC1 were used in a prostate tissue array (> 500 individual tissue cores from 82 patients, 41 case pairs matched with one patient in each pair had biochemical recurrence). Protein expression, quantified in an unbiased manner using an automated analysis protocol in ImageJ software, was increased in malignant vs non-malignant prostate (by 2-2.5 fold, p<0.0001). Operating characteristics indicate sensitivity in the range of 0.68 to 0.74; combination of markers in a logistic regression model demonstrates further improvement in diagnostic power. Triple-labeled immunofluorescence (BTF3, HINT1 and NDRG1) in tissue array showed a significant (p<0.02) change in co-localization coefficients for BTF3 and NDRG1 co-expression in biochemical relapse vs non-relapse cancer epithelium. BTF3, HINT1, NDRG1 and ODC1 could be developed as epithelial specific biomarkers for tissue based diagnosis and stratification of prostate cancer.

  3. Androgen Regulated Genes in Human Prostate Xenografts in Mice: Relation to BPH and Prostate Cancer

    PubMed Central

    Love, Harold D.; Booton, S. Erin; Boone, Braden E.; Breyer, Joan P.; Koyama, Tatsuki; Revelo, Monica P.; Shappell, Scott B.; Smith, Jeffrey R.; Hayward, Simon W.

    2009-01-01

    Benign prostatic hyperplasia (BPH) and prostate carcinoma (CaP) are linked to aging and the presence of androgens, suggesting that androgen regulated genes play a major role in these common diseases. Androgen regulation of prostate growth and development depends on the presence of intact epithelial-stromal interactions. Further, the prostatic stroma is implicated in BPH. This suggests that epithelial cell lines are inadequate to identify androgen regulated genes that could contribute to BPH and CaP and which could serve as potential clinical biomarkers. In this study, we used a human prostate xenograft model to define a profile of genes regulated in vivo by androgens, with an emphasis on identifying candidate biomarkers. Benign transition zone (TZ) human prostate tissue from radical prostatectomies was grafted to the sub-renal capsule site of intact or castrated male immunodeficient mice, followed by the removal or addition of androgens, respectively. Microarray analysis of RNA from these tissues was used to identify genes that were; 1) highly expressed in prostate, 2) had significant expression changes in response to androgens, and, 3) encode extracellular proteins. A total of 95 genes meeting these criteria were selected for analysis and validation of expression in patient prostate tissues using quantitative real-time PCR. Expression levels of these genes were measured in pooled RNAs from human prostate tissues with varying severity of BPH pathologic changes and CaP of varying Gleason score. A number of androgen regulated genes were identified. Additionally, a subset of these genes were over-expressed in RNA from clinical BPH tissues, and the levels of many were found to correlate with disease status. Our results demonstrate the feasibility, and some of the problems, of using a mouse xenograft model to characterize the androgen regulated expression profiles of intact human prostate tissues. PMID:20027305

  4. Biological Differences Between Prostate Cancer Cells that Metastasize to Bone Versus Soft Tissue Sites

    DTIC Science & Technology

    2004-12-01

    retinoic acid inducible in neuroblastoma Homo sapiens, clone IMAGE:4183312, mRNA Homo sapiens, clone IMAGE.a183312, mRNA thlopurine S-methyltransterase...lines compared to normal of human prostatic epithelial cell lines. Non- prostate tissue (see Table I). Immunohis- tumorigenic RWPE-1 prostate epithelial...epithelial cells more than interleukin -1-stimulated human umbilical vein collagen in an integrin-mediated manner [Elga- endothelial cells [Romanov and

  5. Distribution of the AQP4 water channel in normal human tissues: protein and tissue microarrays reveal expression in several new anatomical locations, including the prostate gland and seminal vesicles.

    PubMed

    Mobasheri, Ali; Marples, David; Young, Iain S; Floyd, Rachel V; Moskaluk, Christopher A; Frigeri, Antonio

    2007-01-01

    Aquaporins facilitate osmotically driven water movement across cell membranes. Aquaporin 4 (AQP4) is a major water channel in the central nervous system where it participates in cerebral water balance. AQP4 is also present in basolateral membranes of lower respiratory tract airway and renal collecting duct epithelial cells, gastric parietal cells and skeletal muscle cells. However, the distribution of AQP4 in many other tissues is still unknown. The aim of this study was to determine the expression and relative abundance of AQP4 in human Tissue MicroArrays (TMAs) and human protein microarrays by immunohistochemistry and chemiluminescence. In the central nervous system AQP4 was abundantly expressed in the cerebral cortex, cerebellar cortex (purkinje/granular layer), ependymal cell layer, hippocampus and spinal cord. Lower levels were detected in choroid plexus, white matter and meninges. In the musculoskeletal system AQP4 was highly expressed in the sarcolemma of skeletal muscle from the chest and neck. In the male genital system AQP4 was moderately expressed in seminiferous tubules, seminal vesicles, prostate and epidiymis. In the respiratory system AQP4 was moderately expressed in lung and bronchus. AQP expression was abundant in the kidney. In the gastrointestinal system AQP4 was moderately present in basolateral membranes of parietal cells at the base of gastric glands. AQP4 was also detected in salivary glands, adrenals, anterior pituitary, prostate and seminal vesicles. Human protein microarrays verified the TMA data. Our findings suggest that AQP4 is expressed more widely than previously thought in human organs and may be involved in prostatic and seminal fluid formation.

  6. Benign prostatic hyperplasia: age-related tissue-remodeling.

    PubMed

    Untergasser, Gerold; Madersbacher, Stephan; Berger, Peter

    2005-03-01

    Aging and androgens are the two established risk factors for the development of benign prostatic hyperplasia (BPH) and benign prostatic enlargement (BPE), which can lead to lower urinary tract symptoms (LUTS) in elderly men. BPH, consisting of a nodular overgrowth of the epithelium and fibromuscular tissue within transition zone and periurethral areas, is first detectable around the fourth decade of life and affects nearly all men by the ninth decade. The pathogenesis of BPH is still largely unresolved, but multiple partially overlapping and complementary theories have been proposed, all of which seem to be operative at least to some extent. In addition to nerve-, endocrine- and immune system, local para- and luminocrine pleiotrope mechanisms/factors are implicated in the prostatic tissue-remodeling process. Prostate tissue-remodeling in the transition zone is characterized by: (i) hypertrophic basal cells, (ii) altered secretions of luminal cells leading to calcification, clogged ducts and inflammation, (iii) lymphocytic infiltration with production of proinflammatory cytokines, (iv) increased radical oxygen species (ROS) production that damages epithelial and stromal cells, (v) increased basic fibroblast (bFGF) and transforming growth factor beta (TGF-beta 1) production leading to stromal proliferation, transdifferentiation and extracellular matrix production, (vi) altered autonomous innervation that decreases relaxation and leads to a high adrenergic tonus, (vii) and altered neuroendocine cell function and release of neuroendocrine peptides (NEP). This review summarizes the multifactorial nature of prostate tissue remodeling in elderly men with symptomatic BPH with a particular focus on changes of cell-cell interactions and cell functions in the human aging prostate.

  7. Human papillomavirus and Epstein Barr virus in prostate cancer: Koilocytes indicate potential oncogenic influences of human papillomavirus in prostate cancer.

    PubMed

    Whitaker, Noel J; Glenn, Wendy K; Sahrudin, Arisha; Orde, Matthew M; Delprado, Warick; Lawson, James S

    2013-02-15

    The purpose of this study is to determine if high risk human papillomaviruses (HPV) and Epstein Barr virus (EBV) are both present in the same prostate cancer specimens. We used a range of analytical techniques including in situ polymerase chain reaction (IS-PCR) and standard liquid PCR followed by sequencing of the product to seek to identify HPV and EBV in normal, benign, and malignant prostate tissues. Both HPV type 18 and EBV gene sequences were identified in a high and approximately equal proportion of normal, benign, and prostate cancer specimens. These sequences were located in the nuclei of prostate epithelial cells. HPV associated koilocytes were identified in 24% of prostate cancer specimens. The presence of both HPV and EBV gene sequences in most of the same normal, benign, and malignant prostate specimens is particularly noteworthy because of recent experimental evidence demonstrating that EBV and HPV can collaborate to increase proliferation of cultured cervical cells. Because the presence of EBV and HPV in normal, benign, and malignant prostate tissues appears to be ubiquitous, it is possible that they are harmless. On the other hand HPV type 18 in particular, has high oncogenic potential and may be associated with some prostate cancers. The identification of HPV associated koilocytes in prostate cancer specimens is an indication of HPV infection and potential oncogenic influences of human papillomavirus in prostate cancer. Copyright © 2012 Wiley Periodicals, Inc.

  8. Adipose Tissue Derived Stem Cells Promote Prostate Tumor Growth

    PubMed Central

    Prantl, Lukas; Muehlberg, Fabian; Navone, Nora M.; Song, Yao-Hua; Vykoukal, Jody; Logothetis, Christopher J.; Alt, Eckhard U.

    2016-01-01

    BACKGROUND Recent evidence indicates that cancer stem cells play an important role in tumor initiation and maintenance. Additionally, the effect of tissue-resident stem cells located in the surrounding healthy tissue on tumor progression has been demonstrated. While most knowledge has been derived from studies of breast cancer cells, little is known regarding the influence of tissue resident stem cells on the tumor biology of prostate cancer. METHODS Twenty male athymic Swiss nu/nu mice (age: 6–8 weeks) were randomized into two treatment groups: 1) subcutaneous injection of 106 MDA PCa 118b human prostate cancer cells into the upper back or 2) subcutaneous injection of 106 MDA PCa 118b cells mixed directly with 105 GFP-labeled human adipose tissue-derived stem cells (hASCs). Tumor growth and volumes over the ensuing 3 weeks were assessed using calipers and micro-computed tomography. Immunohistochemistry was performed to identify engrafted hASCs in tumor sections. RESULTS At 3 weeks after injection, the mean tumor volume in the MDA PCa 118b/hASC co-injection group (1019.95 ± 73.49 mm3) was significantly higher than that in the MDA PCa 118b-only group (308.70 ± 21.06 mm3). Engrafted hASCs exhibited the nuclear marker of proliferation Ki67 and expressed markers for endothelial differentiation, indicating their engraftment in tumor vessels. CONCLUSION Our study revealed for the first time that ASCs subcutaneously co-injected with prostate cancer cells engraft and promote tumor progression. Further evaluation of the cross-talk between tumor and local tissue-resident stem cells may lead to new strategies for prostate cancer therapy. PMID:20564322

  9. Microlocalization and Quantitation of Risk Associated Elements in Gleason Graded Prostate Tissue

    DTIC Science & Technology

    2005-03-01

    non-tumor human prostate tissue. FASEB J. 2004; 18:A351.3 (351.3). Barranco W.T. and Eckhert C.D. Boric acid inhibits human prostate cancer cell...pay from the research effort. Kim Henderson (Student) Joey Miller (Student) Wade Barranco (Student) Curtis Eckhert (PI) CONCLUSIONS The project is on...selenium and elements associated with cancer risk in non-tumor human prostate tissue. FASEB J. 2004; 18:A351.3 (351.3). 16. Barranco W.T. and Eckhert C.D

  10. Liquid chromatography-mass spectrometry of cis- and all-trans-lycopene in human serum and prostate tissue after dietary supplementation with tomato sauce.

    PubMed

    van Breemen, Richard B; Xu, Xiaoying; Viana, Marlos A; Chen, Longwen; Stacewicz-Sapuntzakis, Maria; Duncan, Claudine; Bowen, Phyllis E; Sharifi, Roohollah

    2002-04-10

    Several epidemiological studies suggest a lower incidence of prostate cancer in men who routinely consume tomato products. Tomatoes are the primary dietary source of lycopene, which is among the most potent antioxidants of the carotenoids. Men with clinical stage T1 or T2 prostate adenocarcinoma were recruited (n = 32) and consumed tomato sauce based pasta dishes for 3 weeks (equivalent to 30 mg of lycopene per day) before radical prostectomy. Prostate tissue from needle biopsy just before intervention and prostectomy after supplementation from a subset of 11 subjects was evaluated for both total lycopene and lycopene geometrical isomer ratios. A gradient HPLC system using a C(18) column with UV-vis absorbance detection was used to measure total lycopene. Because the absorbance detector was insufficiently sensitive, HPLC with a C(30) column and positive ion atmospheric pressure chemical ionization mass spectrometric (LC-MS) detection was developed as a new assay to measure the ratio of lycopene cis/trans isomers in these samples. The limit of detection of the LC-MS method was determined to be 0.93 pmol of lycopene on-column, and a linear response was obtained over 3 orders of magnitude. Total lycopene in serum increased 2.0-fold from 35.6 to 69.9 microg/dL (from 0.664 to 1.30 microM) as a result of dietary supplementation with tomato sauce, whereas total lycopene in prostate tissue increased 3.0-fold from 0.196 to 0.582 ng/mg of tissue (from 0.365 to 1.09 pmol/mg). all-trans-Lycopene and at least 14 cis-isomer peaks were detected in prostate tissue and serum. The mean proportion of all-trans-lycopene in prostate tissue was approximately 12.4% of total lycopene before supplementation but increased to 22.7% after dietary intervention with tomato sauce. In serum there was only a 2.8% but statistically significant increase in the proportion of all-trans-lycopene after intervention. These results indicate that short-term supplementation with tomato sauce containing

  11. Finasteride treatment alters tissue specific androgen receptor expression in prostate tissues.

    PubMed

    Bauman, Tyler M; Sehgal, Priyanka D; Johnson, Karen A; Pier, Thomas; Bruskewitz, Reginald C; Ricke, William A; Huang, Wei

    2014-06-01

    Normal and pathologic growth of the prostate is dependent on the synthesis of dihydrotestosterone (DHT) from testosterone by 5α-reductase. Finasteride is a selective inhibitor of 5α-reductase 2, one isozyme of 5α-reductase found in abundance in the human prostate. The objective of this study was to investigate the effects of finasteride on androgen receptor expression and tissue morphology in human benign prostatic hyperplasia specimens. Patients undergoing transurethral resection of the prostate and either treated or not treated with finasteride between 2004 and 2010 at the University of Wisconsin-Hospital were retrospectively identified using an institutional database. Prostate specimens from each patient were triple-stained for androgen receptor, prostate-specific antigen, and basal marker cytokeratin 5. Morphometric analysis was performed using the multispectral imaging, and results were compared between groups of finasteride treated and non-treated patients. Epithelial androgen receptor but not stromal androgen receptor expression was significantly lower in patients treated with finasteride than in non-treated patients. Androgen receptor-regulated prostate-specific antigen was not significantly decreased in finasteride-treated patients. Significant luminal epithelial atrophy and basal cell hyperplasia were prevalent in finasteride treated patients. Epithelial androgen receptor expression was highly correlated to the level of luminal epithelial atrophy. In this study, finasteride decreased the expression of epithelial androgen receptor in a tissue specific manner. The correlation between epithelial androgen receptor and the extent of luminal epithelial atrophy suggests that epithelial androgen receptor may be directly regulating the atrophic effects observed with finasteride treatment. © 2014 Wiley Periodicals, Inc.

  12. Finasteride Treatment Alters Tissue Specific Androgen Receptor Expression in Prostate Tissues

    PubMed Central

    Bauman, Tyler M.; Sehgal, Priyanka D.; Johnson, Karen A.; Pier, Thomas; Bruskewitz, Reginald C.; Ricke, William A.; Huang, Wei

    2014-01-01

    BACKGROUND Normal and pathologic growth of the prostate is dependent on the synthesis of dihydrotestosterone (DHT) from testosterone by 5α-reductase. Finasteride is a selective inhibitor of 5α-reductase 2, one isozyme of 5α-reductase found in abundance in the human prostate. The objective of this study was to investigate the effects of finasteride on androgen receptor expression and tissue morphology in human benign prostatic hyperplasia specimens. METHODS Patients undergoing transurethral resection of the prostate and either treated or not treated with finasteride between 2004 and 2010 at the University of Wisconsin-Hospital were retrospectively identified using an institutional database. Prostate specimens from each patient were triple-stained for androgen receptor, prostate-specific antigen, and basal marker cytokeratin 5. Morphometric analysis was performed using the multispectral imaging, and results were compared between groups of finasteride treated and non-treated patients. RESULTS Epithelial androgen receptor but not stromal androgen receptor expression was significantly lower in patients treated with finasteride than in non-treated patients. Androgen receptor-regulated prostate-specific antigen was not significantly decreased in finasteride-treated patients. Significant luminal epithelial atrophy and basal cell hyperplasia were prevalent in finasteride treated patients. Epithelial androgen receptor expression was highly correlated to the level of luminal epithelial atrophy. CONCLUSIONS In this study, finasteride decreased the expression of epithelial androgen receptor in a tissue specific manner. The correlation between epithelial androgen receptor and the extent of luminal epithelial atrophy suggests that epithelial androgen receptor may be directly regulating the atrophic effects observed with finasteride treatment. PMID:24789081

  13. Sex steroid receptor expression and localization in benign prostatic hyperplasia varies with tissue compartment

    PubMed Central

    Nicholson, Tristan M.; Sehgal, Priyanka D.; Drew, Sally A.; Huang, Wei; Ricke, William A.

    2013-01-01

    Androgens and estrogens, acting via their respective receptors, are important in benign prostatic hyperplasia (BPH). The goal of this study was to quantitatively characterize the tissue distribution and staining intensity of androgen receptor (AR) and estrogen receptor-alpha (ERα), and assess cells expressing both AR and ERα, in human BPH compared to normal prostate. A tissue microarray composed of normal prostate and BPH tissue was used and multiplexed immunohistochemistry was performed to detect AR and ERα. We used a multispectral imaging platform for automated scanning, tissue and cell segmentation and marker quantification. BPH specimens had an increased number of epithelial and stromal cells and increased percentage of epithelium. In both stroma and epithelium, the mean nuclear area was decreased in BPH relative to normal prostate. AR expression and staining intensity in epithelial and stromal cells was significantly increased in BPH compared to normal prostate. ERα expression was increased in BPH epithelium. However, stromal ERα expression and staining intensity was decreased in BPH compared to normal prostate. Double positive (AR & ERα) epithelial cells were more prevalent in BPH, and fewer double negative (AR & ERα) stromal and epithelial negative cells were observed in BPH. These data underscore the importance of tissue layer localization and expression of steroid hormone receptors in the prostate. Understanding the tissue-specific hormone action of androgens and estrogens will lead to a better understanding of mechanisms of pathogenesis in the prostate and may lead to better treatment for BPH. PMID:23792768

  14. Tissue Biomarkers for Prostate Cancer Radiation Therapy

    PubMed Central

    Tran, PT; Hales, RK; Zeng, J; Aziz, K; Salih, T; Gajula, RP; Chettiar, S; Gandhi, N; Wild, AT; Kumar, R; Herman, JM; Song, DY; DeWeese, TL

    2012-01-01

    Prostate cancer is the most common cancer and second leading cause of cancer deaths among men in the United States. Most men have localized disease diagnosed following an elevated serum prostate specific antigen test for cancer screening purposes. Standard treatment options consist of surgery or definitive radiation therapy directed by clinical factors that are organized into risk stratification groups. Current clinical risk stratification systems are still insufficient to differentiate lethal from indolent disease. Similarly, a subset of men in poor risk groups need to be identified for more aggressive treatment and enrollment into clinical trials. Furthermore, these clinical tools are very limited in revealing information about the biologic pathways driving these different disease phenotypes and do not offer insights for novel treatments which are needed in men with poor-risk disease. We believe molecular biomarkers may serve to bridge these inadequacies of traditional clinical factors opening the door for personalized treatment approaches that would allow tailoring of treatment options to maximize therapeutic outcome. We review the current state of prognostic and predictive tissue-based molecular biomarkers which can be used to direct localized prostate cancer treatment decisions, specifically those implicated with definitive and salvage radiation therapy. PMID:22292443

  15. Role of Plasma Discharge in Division of Prostatic Tissue

    NASA Astrophysics Data System (ADS)

    Ward, Arlen; Almgren, Carl; Yu, Zeng-Qi; Sartor, Joe; Collins, George

    2009-10-01

    During the treatment of benign prostatic hyperplasia electrical energy is used to separate prostatic tissue and remove it as a urinary obstruction. This surgical procedure is often performed in a saline environment, and current paths change as the tissue and fluid are heated. This study shows that a plasma discharge at the electrode is necessary to provide the current densities necessary to vaporize portions of the prostatic tissue in order to facilitate removal. This behavior is predicted in finite element simulations, and verified with color schlieren imaging and ex vivo bovine prostate tests.

  16. Inverse association between gluthathione peroxidase activity and both selenium-binding protein 1 levels and gleason score in human prostate tissue

    USDA-ARS?s Scientific Manuscript database

    BACKGROUND. Data from human epidemiological studies, cultured mammalian cells, and animal models have supported a potentially beneficial role of selenium (Se) in prostate cancer prevention. In addition, Se-containing proteins including members of the gutathione peroxidase (GPx) family and Selenium-B...

  17. Voltage-gated sodium channels were differentially expressed in human normal prostate, benign prostatic hyperplasia and prostate cancer cells.

    PubMed

    Shan, Bin; Dong, Mei; Tang, He; Wang, Na; Zhang, Jin; Yan, Changqing; Jiao, Xiaocui; Zhang, Hailin; Wang, Chuan

    2014-07-01

    Voltage-gated sodium channels (VGSCs) are expressed not only in excitable cells but also in numerous metastatic cells, particularly in certain types of cancer cells. In some types of cancer, including prostate cancer, the expression of VGSCs is associated with cancer migration, invasion and metastasis in vivo. However, the detailed expression profiles of VGSC α subunits in normal human prostate, in prostatic hyperplasia and prostatic cancer remain controversial. In the present study, quantitative polymerase chain reaction was used to systematically detect all subtypes of VGSC α subunits in normal human prostate, benign prostatic hyperplasia (BPH) and prostate cancer cells. The expression profile of VGSC α subunits was observed to differ between these cell types. Nav1.5 was the major isoform expressed in normal human prostate tissue, while Nav1.5 and Nav1.2 were the predominant isoforms in BPH tissue. However, in PC-3 and LNCaP cells, two typical prostate cancer cell lines, Nav1.6 and Nav1.7 were abundantly expressed. By comparing the relative expression levels of Nav1.5, Nav1.6 and Nav1.7 in these cells, the mRNA levels of Nav1.6 and Nav1.7 were identified to be 6- to 27-fold higher in PC-3 and LNCaP cells than in either normal or BPH samples (P<0.05); however, Nav1.5 mRNA levels were relatively lower compared with those of Nav1.6 or Nav1.7 in all cells analyzed. To confirm whether Nav1.6 and Nav1.7 expression in cancer cells was functional, a patch-clamp technique was used to record whole-cell currents. A tetrodotoxin-sensitive sodium current was successfully recorded in PC-3 cells, but not in LNCaP cells. It was concluded that although all types of VGSC α subunits exhibited low expression levels in normal prostate and BPH cells, both Nav1.6 and Nav1.7 were significantly upregulated in the prostate cancer cell lines, suggesting these subtypes may be potential diagnostic markers and therapeutic targets for certain types of prostate cancer in humans.

  18. Intercellular communication and human prostate carcinogenesis.

    PubMed

    Carruba, Giuseppe; Stefano, Rosalba; Cocciadiferro, Letizia; Saladino, Francesca; Di Cristina, Antonietta; Tokar, Erik; Quader, Salmann T A; Webber, Mukta M; Castagnetta, Luigi

    2002-06-01

    Gap-junction-mediated intercellular communication (GJIC) is required for completion of embryonic development, tissue homeostasis, and regulation of cell proliferation and death. Although, as emphasized in several reports, defects or disruption of GJIC may be important in carcinogenesis, the potential role of GJIC in the onset and progression of human prostate cancer remains ill-defined. The gap junction channel-forming connexins (Cx) comprise a multigene family of highly conserved proteins that are differentially expressed in a tissue- and development-specific manner; changes in connexin expression are also commonly seen during cellular differentiation. However, when multiple connexins are concurrently expressed, gap junction channels may consist of more than one connexin species. This is important, because only certain pairings give rise to functional channels. In our studies, we investigated GJIC in a panel of both nontumorigenic (RWPE-1) and malignant (RWPE-2, LNCaP, DU-145) human prostate epithelial cells, compared to a normal rat liver epithelial F344 (WB-1) cell line, as it was found to be junctionally proficient. In addition, expression and regulation of Cx43 and Cx32 were also inspected using western blot analysis. The ability of hormones, antihormones, and the antihypertensive drug forskolin to restore GJIC in nontumorigenic and malignant human prostate epithelial cells was examined by the scrape-loading/dye transfer (SL/DT) or fluorescence recovery after photobleaching (FRAP) methods using an Ultima laser cytometer. Results from both assays showed that neither nontumorigenic nor malignant prostate cells have functional GJIC. However, both estrone (E1) and forskolin (FK) induced a significant increase (4.4- and 2.8-fold, respectively) in cell-cell communication only in the RWPE-1 cells. Interestingly, the use of Matrigel, a solubilized basement membrane, as substrate for cell attachment and growth resulted in the rescue of GJIC activity in RWPE-1 cells, as

  19. Application of vibro-acoustography in prostate tissue imaging

    PubMed Central

    Alizad, Azra; Mehrmohammadi, Mohammad; Mitri, Farid G.; Davis, Brian J.; Sebo, Thomas J.; Mynderse, Lance A.; Kinnick, Randall R.; Greenleaf, James F.; Fatemi, Mostafa

    2013-01-01

    Purpose: To evaluate the potential of the imaging modality vibro-acoustography (VA) for imaging of the prostate. Methods: Excised cadaver prostate specimens were embedded in tissue mimicking gel to simulate the properties of surrounding soft tissues. The samples were imaged at various depths using a laboratory prototyped VA imaging system. The recorded signals were used for offline processing and image reconstruction. In a selected subgroup of tissue samples, conventional ultrasound (B-mode) and x-ray imaging were performed for further analysis, evaluation, and validation of the VA images. Results: The imaging results of prostate tissue samples indicate the capability of VA imaging to detect prostatic nodules and lesions. In the prostate sample with an adenocarcinoma, the lesion appears with a clear contrast with respect to its surrounding tissue. The VA images could also identify the presence of calcifications deep inside the prostate tissue. Further, quantifications of the imaging results demonstrate that VA imaging has higher sensitivity to detect the calcifications compared to conventional ultrasound imaging. VA is also capable of visualizing prostatic tissue structures and in some cases can identify the anatomical zones. More specifically, the observed higher texture level in peripheral zones demonstrates the ability of VA to differentiate between prostatic anatomical zones. Conclusions: Imaging results of ex vivo prostate tissues, reveals the potency of VA as a promising tool to detect abnormalities, delineate tissue structures and anatomical zones, and locate calcifications. The results of this pilot study suggest that in vivo VA imaging of the prostate may be of clinical utility. PMID:23387773

  20. Characterizing the stiffness of Human Prostates using Acoustic Radiation Force

    PubMed Central

    Zhai, Liang; Madden, John; Foo, Wen-Chi; Mouraviev, Vladimir; Polascik, Thomas J.; Palmeri, Mark L.; Nightingale, Kathryn R.

    2012-01-01

    Acoustic Radiation Force Impulse (ARFI) imaging has been previously reported to portray normal anatomic structures and pathologies in ex vivo human prostates with good contrast and resolution. These findings were based on comparison with histological slides and McNeal’s zonal anatomy. In ARFI images, the central zone (CZ) appears darker (smaller displacement) than other anatomic zones, and prostate cancer (PCa) is darker than normal tissue in the peripheral zone (PZ). Since displacement amplitudes in ARFI images are determined by both the underlying tissue stiffness and the amplitude of acoustic radiation force which varies with acoustic attenuation, one question that arises is: how are the relative displacements in prostate ARFI images related to the underlying prostatic tissue stiffness? In linear, isotropic elastic materials and in tissues that are relatively uniform in acoustic attenuation (e.g. liver), relative displacement in ARFI images has been shown to be correlated with underlying tissue stiffness. However, the prostate is known to be heterogeneous. Variations in acoustic attenuation of prostatic structures could confound the interpretation of ARFI images due to the associated variations in the applied acoustic radiation force. Therefore, in this study, co-registered three-dimensional (3D) ARFI datasets and quantitative shear wave elasticity imaging (SWEI) datasets were acquired in freshly excised human prostates to investigate the relationship between displacement amplitudes in ARFI prostate images and the matched reconstructed shear moduli. The lateral time-to-peak (LTTP) algorithm was applied to the SWEI data to compute the shear wave speed and reconstruct the shear moduli. Five types of prostatic tissue (PZ, CZ, transition zone (TZ) and benign prostatic hyperplasia (BPH), PCa, and atrophy) were identified, whose shear moduli were quantified to be 4.1±0.8 kPa, 9.9±0.9 kPa, 4.8±0.6 kPa, 10.0±1.0 kPa and 8.0 kPa, respectively. Linear regression was

  1. Characterizing stiffness of human prostates using acoustic radiation force.

    PubMed

    Zhai, Liang; Madden, John; Foo, Wen-Chi; Mouraviev, Vladimir; Polascik, Thomas J; Palmeri, Mark L; Nightingale, Kathryn R

    2010-10-01

    Acoustic Radiation Force Impulse (ARFI) imaging has been previously reported to portray normal anatomic structures and pathologies in ex vivo human prostates with good contrast and resolution. These findings were based on comparison with histological slides and McNeal's zonal anatomy. In ARFI images, the central zone (CZ) appears darker (smaller displacement) than other anatomic zones and prostate cancer (PCa) is darker than normal tissue in the peripheral zone (PZ). Since displacement amplitudes in ARFI images are determined by both the underlying tissue stiffness and the amplitude of acoustic radiation force that varies with acoustic attenuation, one question that arises is how the relative displacements in prostate ARFI images are related to the underlying prostatic tissue stiffness. In linear, isotropic elastic materials and in tissues that are relatively uniform in acoustic attenuation (e.g., liver), relative displacement in ARFI images has been shown to be correlated with underlying tissue stiffness. However, the prostate is known to be heterogeneous. Variations in acoustic attenuation of prostatic structures could confound the interpretation of ARFI images due to the associated variations in the applied acoustic radiation force. Therefore, in this study, co-registered three-dimensional (3D) ARFI datasets and quantitative shear wave elasticity imaging (SWEI) datasets were acquired in freshly-excised human prostates to investigate the relationship between displacement amplitudes in ARFI prostate images and the matched reconstructed shear moduli. The lateral time-to-peak (LTTP) algorithm was applied to the SWEI data to compute the shear-wave speed and reconstruct the shear moduli. Five types of prostatic tissue (PZ, CZ, transition zone (TZ) and benign prostatic hyperplasia (BPH), PCa and atrophy) were identified, whose shear moduli were quantified to be 4.1 +/- 0.8 kPa, 9.9 +/- 0.9 kPa, 4.8 +/- 0.6 kPa, 10.0 +/- 1.0 kPa and 8.0 kPa, respectively. Linear

  2. High resolution regional elasticity mapping of the human prostate.

    PubMed

    Murayama, Yoshinobu; Omata, Sadao; Yajima, Toshikuni; Peng, Qiyu; Shishido, Keiichi; Peehl, Donna M; Constantinou, Christos E

    2007-01-01

    What is it that the clinician "feels" during a digital rectal examination? To answer this question, it is necessary to measure the elastic properties of the prostate and verify the stiffness values with histological examination. Therefore, we devised an Elasticity Mapping System to evaluate the elastic properties of various histopathological grades of prostate cancer in relation to benign prostatic hyperplasia (BPH) and normal tissue. The system consists of a micro tactile sensor, a three-axis (XYZ) with one (fine Z) micromanipulation stage, a stereoscope camera and a measurement chamber. Using this methodology we mapped the elasticity of human prostate cancer (CaP) and it was obviously observed that the node was significantly harder than surrounding normal tissues and had some textures.

  3. Arachidonic acid metabolism in human prostate cancer

    PubMed Central

    YANG, PEIYING; CARTWRIGHT, CARRIE A.; LI, JIN; WEN, SIJIN; PROKHOROVA, INA N.; SHUREIQI, IMAD; TRONCOSO, PATRICIA; NAVONE, NORA M.; NEWMAN, ROBERT A.; KIM, JERI

    2012-01-01

    The arachidonic acid pathway is important in the development and progression of numerous malignant diseases, including prostate cancer. To more fully evaluate the role of individual cyclooxygenases (COXs), lipoxygenases (LOXs) and their metabolites in prostate cancer, we measured mRNA and protein levels of COXs and LOXs and their arachidonate metabolites in androgen-dependent (LNCaP) and androgen-independent (PC-3 and DU145) prostate cancer cell lines, bone metastasis-derived MDA PCa 2a and MDA PCa 2b cell lines and their corresponding xenograft models, as well as core biopsy specimens of primary prostate cancer and nonneoplastic prostate tissue taken ex vivo after prostatectomy. Relatively high levels of COX-2 mRNA and its product PGE2 were observed only in PC-3 cells and their xenografts. By contrast, levels of the exogenous 12-LOX product 12-HETE were consistently higher in MDA PCa 2b and PC-3 cells and their corresponding xenograft tissues than were those in LNCaP cells. More strikingly, the mean endogenous level of 12-HETE was significantly higher in the primary prostate cancers than in the nonneoplastic prostate tissue (0.094 vs. 0.010 ng/mg protein, respectively; p=0.019). Our results suggest that LOX metabolites such as 12-HETE are critical in prostate cancer progression and that the LOX pathway may be a target for treating and preventing prostate cancer. PMID:22895552

  4. Photodynamic therapy in prostate cancer: optical dosimetry and response of normal tissue

    NASA Astrophysics Data System (ADS)

    Chen, Qun; Shetty, Sugandh D.; Heads, Larry; Bolin, Frank; Wilson, Brian C.; Patterson, Michael S.; Sirls, Larry T., II; Schultz, Daniel; Cerny, Joseph C.; Hetzel, Fred W.

    1993-06-01

    The present study explores the possibility of utilizing photodynamic therapy (PDT) in treating localized prostate carcinoma. Optical properties of ex vivo human prostatectomy specimens, and in vivo and ex vivo dog prostate glands were studied. The size of the PDT induced lesion in dog prostate was pathologically evaluated as a biological endpoint. The data indicate that the human normal and carcinoma prostate tissues have similar optical properties. The average effective attenuation depth is less in vivo than that of ex vivo. The PDT treatment generated a lesion size of up to 16 mm in diameter. The data suggest that PDT is a promising modality in prostate cancer treatment. Multiple fiber system may be required for clinical treatment.

  5. Expression in human prostate of drug- and carcinogen-metabolizing enzymes: association with prostate cancer risk.

    PubMed Central

    Agúndez, J. A.; Martínez, C.; Olivera, M.; Gallardo, L.; Ladero, J. M.; Rosado, C.; Prados, J.; Rodriguez-Molina, J.; Resel, L.; Benítez, J.

    1998-01-01

    The role of two common polymorphisms of enzymes involved in the metabolism of drugs and carcinogens was studied in relation to prostate cancer. The gene encoding one of these enzymes (NAT2) is located in an area where frequent allelic loss occurs in prostate cancer. Mutations at the genes CYP2D6 and NAT2 were analysed by allele-specific polymerase chain reaction and restriction mapping in DNA from 94 subjects with prostate cancer and 160 male healthy control subjects. Eleven prostate specimens were analysed for genotype and enzymatic activities NAT2, CYP2D6 and CYP3A by using the enzyme-specific substrates sulphamethazine and dextromethorphan. Enzyme activities with substrate specificities corresponding to NAT2, CYP2D6 and CYP3A are present in human prostate tissue, with mean +/-s.d. activities of 4.8+/-4.4 pmol min(-1) mg(-1) protein, 156+/-91 and 112+/-72 nmol min(-1) mg(-1) protein respectively. The Km values for the prostate CYP2D6 and CYP3A enzyme activities corresponded to that of liver CYP2D6 and CYP3A activities, and the CYP2D6 enzyme activity is related to the CYP2D6 genotype. The N-acetyltransferase, in contrast, had a higher Km than NAT2 and was independent of the NAT2 genotype. The CYP2D6 and CYP3A enzymes, and an N-acetyltransferase activity that is independent of the regulation of the NAT2 gene, are expressed in human prostate tissue. The presence of carcinogen-metabolizing enzymes in human prostate with a high interindividual variability may be involved in the regulation of local levels of carcinogens and mutagens and may underlie interindividual differences in cancer susceptibility. Images Figure 1 PMID:9823980

  6. Endometase in Androgen-Repressed Human Prostate Cancer

    DTIC Science & Technology

    2005-03-01

    intraepithelial neoplasia from multiple patients were significantly higher than those in prostatitis, benign prostate hyperplasia, and normal prostate glandular...prostate cancer cell invasion. 3. We showed that the levels of MMP-26 protein in human prostate carcinomas from multiple patients were significantly...inhibitors of MMP-26 block prostate cancer invasion. We have showed that the levels of MMP-26 protein in human prostate carcinomas from multiple patients were

  7. A human prostatic bacterial isolate alters the prostatic microenvironment and accelerates prostate cancer progression

    PubMed Central

    Simons, Brian W; Durham, Nicholas M; Bruno, Tullia C; Grosso, Joseph F; Schaeffer, Anthony J; Ross, Ashley E; Hurley, Paula J; Berman, David M; Drake, Charles G; Thumbikat, Praveen; Schaeffer, Edward M

    2015-01-01

    Inflammation is associated with several diseases of the prostate including benign enlargement and cancer, but a causal relationship has not been established. Our objective was to characterize the prostate inflammatory microenvironment after infection with a human prostate-derived bacterial strain and to determine the effect of inflammation on prostate cancer progression. To this end, we mimicked typical human prostate infection with retrograde urethral instillation of CP1, a human prostatic isolate of Escherichia coli. CP1 bacteria were tropic for the accessory sex glands and induced acute inflammation in the prostate and seminal vesicles, with chronic inflammation lasting at least 1 year. Compared to controls, infection induced both acute and chronic inflammation with epithelial hyperplasia, stromal hyperplasia, and inflammatory cell infiltrates. In areas of inflammation, epithelial proliferation and hyperplasia often persist, despite decreased expression of androgen receptor (AR). Inflammatory cells in the prostates of CP1-infected mice were characterized at 8 weeks post-infection by flow cytometry, which showed an increase in macrophages and lymphocytes, particularly Th17 cells. Inflammation was additionally assessed in the context of carcinogenesis. Multiplex cytokine profiles of inflamed prostates showed that distinct inflammatory cytokines were expressed during prostate inflammation and cancer, with a subset of cytokines synergistically increased during concurrent inflammation and cancer. Furthermore, CP1 infection in the Hi-Myc mouse model of prostate cancer accelerated the development of invasive prostate adenocarcinoma, with 70% more mice developing cancer by 4.5 months of age. This study provides direct evidence that prostate inflammation accelerates prostate cancer progression and gives insight into the microenvironment changes induced by inflammation that may accelerate tumour initiation or progression. PMID:25348195

  8. Prostatic Tissue Elimination After Prostatic Artery Embolization (PAE): A Report of Three Cases.

    PubMed

    Leite, Leandro Cardarelli; de Assis, Andre Moreira; Moreira, Airton Mota; Harward, Sardis Honoria; Antunes, Alberto Azoubel; Carnevale, Francisco Cesar

    2017-06-01

    We report three cases of spontaneous prostatic tissue elimination through the urethra while voiding following technically successful prostatic artery embolization (PAE) as a treatment for lower urinary tract symptoms (LUTS) related to benign prostatic hyperplasia (BPH). All patients were embolized with 100- to 300-μm microspheres alone or in combination with 300- to 500-μm microspheres. During follow-up prior to eliminating the tissue fragments, the three patients all presented with intermittent periods of LUTS improvement and aggravation. After expelling the prostatic tissue between 1 and 5 months of follow-up, significant improvements in LUTS and urodynamic parameters were observed in all patients. Urethral obstruction after PAE caused by sloughing prostate tissue is a potential complication of the procedure and should be considered in patients with recurrent LUTS in order to avoid inappropriate management.

  9. MicroRNA-181b expression in prostate cancer tissues and its influence on the biological behavior of the prostate cancer cell line PC-3.

    PubMed

    He, L; Yao, H; Fan, L H; Liu, L; Qiu, S; Li, X; Gao, J P; Hao, C Q

    2013-04-02

    We examined microRNA-181b (miRNA) expression in prostate cancer tissues and its effect on the prostate cancer cell line PC-3. Tissues from 27 cases of prostate cancer and 30 samples of normal human prostate were collected by surgical removal. Total miRNA was extracted, and the relative expression of miR-181b was quantified using RT-PCR. miR-181b ASO was transfected into prostate cancer PC-3 cells. miR-181b expression in transfected and non-transfected cells was measured using RT-PCR. Changes in cell apoptosis were measured using flow cytometry. MTT and cell growth curve methods were used to assess the influence of miR-181b expression on cell proliferation. The changes in cell invasive ability in vitro were detected using the Transwell chamber method. miR-181b was up-regulated in the prostate cancer tissues compared with the normal prostate samples. It was down-regulated after miR-181b ASO transfection into the prostate cancer PC-3 cells. Down-regulation of miR-181b in the PC-3 cell induced apoptosis, inhibited proliferation, and depressed invasion of PC-3 cells in vitro. As miR-181b is over-expressed in prostate cancer, its down-regulation could have potential as gene therapy for prostate cancer by inducing apoptosis, inhibiting proliferation and depressing invasion by cancer cells.

  10. Inorganic Arsenic and Human Prostate Cancer

    PubMed Central

    Benbrahim-Tallaa, Lamia; Waalkes, Michael P.

    2008-01-01

    Objective We critically evaluated the etiologic role of inorganic arsenic in human prostate cancer. Data sources We assessed data from relevant epidemiologic studies concerning environmental inorganic arsenic exposure. Whole animal studies were evaluated as were in vitro model systems of inorganic arsenic carcinogenesis in the prostate. Data synthesis Multiple studies in humans reveal an association between environmental inorganic arsenic exposure and prostate cancer mortality or incidence. Many of these human studies provide clear evidence of a dose–response relationship. Relevant whole animal models showing a relationship between inorganic arsenic and prostate cancer are not available. However, cellular model systems indicate arsenic can induce malignant transformation of human prostate epithelial cells in vitro. Arsenic also appears to impact prostate cancer cell progression by precipitating events leading to androgen independence in vitro. Conclusion Available evidence in human populations and human cells in vitro indicates that the prostate is a target for inorganic arsenic carcinogenesis. A role for this common environmental contaminant in human prostate cancer initiation and/or progression would be very important. PMID:18288312

  11. The role of human papillomavirus infection in prostate carcinoma.

    PubMed

    Aghakhani, Arezoo; Hamkar, Rasool; Parvin, Mahmoud; Ghavami, Nastaran; Nadri, Mahsa; Pakfetrat, Attesa; Banifazl, Mohammad; Eslamifar, Ali; Izadi, Nabiollah; Jam, Sara; Ramezani, Amitis

    2011-01-01

    Human papillomavirus (HPV) infections are associated with benign and malignant lesions of the female and male anogenital tract. Currently the possible role of HPV infections in prostate carcinogenesis is a subject of great controversy. In this study we aimed to investigate the role of HPV infection in prostate carcinoma (PCa). The study included formalin-fixed paraffin-embedded tissue samples of 104 primary prostate adenocarcinoma cases and 104 control tissues of benign prostatic hyperplasia (BPH). HPV-DNA was purified and amplified through MY09/MY11 and GP5(+)/GP6(+) primers and subsequently subjected to sequencing. HPV-DNA was found in 13 of 104 (12.5%) PCa and 8 of 104 (7.7%) BPH samples. High-risk HPVs were detected in 10 of 13 (76.9%) PCa and 5 of 8 (62.5%) BPH samples with positive HPV-DNA. Low-risk HPVs were detected in 3 of 13 (23.1%) PCa and 3 of 8 (37.5%) BPH specimens with positive HPV-DNA. There was no significant difference between PCa and BPH specimens regarding HPV-DNA presence or the detection of high-risk and low-risk types of HPV. Our data do not support the role of HPV infection in prostate carcinoma. Further studies are required to elucidate the role of HPV infection in human prostate carcinogenesis.

  12. Involvement of human papillomavirus infections in prostate cancer progression.

    PubMed

    Al Moustafa, Ala-Eddin

    2008-08-01

    High-risk human papillomaviruses (HPVs) are sexually transmitted and have been associated with several human carcinomas especially cervical and colorectal. On the other hand, a small number of studies have examined the presence of high-risk HPV in human prostate cancer tissues. Currently, the presence and role of high-risk HPV infections in prostate carcinogenesis remain unclear because of the limited number of investigations. This raises the question whether high-risk HPV infections play any role in human prostate cancer development. However, other investigators and our group were able to immortalize normal and cancer prostate epithelial cells in vitro by E6/E7 of HPV type 16. In this paper, we propose the hypothesis that normal and cancer prostate epithelial cells are susceptible to persistent HPV infections; therefore, high-risk HPV infections play an important role in the progression of prostate cancer. We believe that an international collaboration of epidemiological studies and more molecular biology investigations are necessary to answer these important questions.

  13. Retinoic acid and androgen receptors combine to achieve tissue specific control of human prostatic transglutaminase expression: a novel regulatory network with broader significance

    PubMed Central

    Rivera-Gonzalez, Guillermo C.; Droop, Alastair P.; Rippon, Helen J.; Tiemann, Katrin; Pellacani, Davide; Georgopoulos, Lindsay J.; Maitland, Norman J.

    2012-01-01

    In the human prostate, expression of prostate-specific genes is known to be directly regulated by the androgen–induced stimulation of the androgen receptor (AR). However, less is known about the expression control of the prostate-restricted TGM4 (hTGP) gene. In the present study we demonstrate that the regulation of the hTGP gene depends mainly on retinoic acid (RA). We provide evidence that the retinoic acid receptor gamma (RAR-G) plays a major role in the regulation of the hTGP gene and that presence of the AR, but not its transcriptional transactivation activity, is critical for hTGP transcription. RA and androgen responsive elements (RARE and ARE) were mapped to the hTGP promoter by chromatin immunoprecipitation (ChIP), which also indicated that the active ARE and RARE sites were adjacent, suggesting that the antagonistic effect of androgen and RA is related to the relative position of binding sites. Publicly available AR and RAR ChIP-seq data was used to find gene potentially regulated by AR and RAR. Four of these genes (CDCA7L, CDK6, BTG1 and SAMD3) were tested for RAR and AR binding and two of them (CDCA7L and CDK6) proved to be antagonistically regulated by androgens and RA confirming that this regulation is not particular of hTGP. PMID:22362749

  14. Biomarkers of Oxidative Injury and Their Modulation in Prostate Tissue from Patients with Prostatic Tissue from Patients with Prostate Cancer

    DTIC Science & Technology

    2003-03-01

    several of these agents, including vitamin E and sulindac , may be protective against prostate and other epithelial cancers (7) (8). In fact, there is in...vitro data suggesting that human PCa cell line growth is also inhibited by sulindac treatment (9). There is conflicting data on whether consumption of...Celano, P., Booker, S.V., Robinson, C.R. and Offerhaus, G.J., Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis

  15. Discovery and Classification of Fusion Transcripts in Prostate Cancer and Normal Prostate Tissue.

    PubMed

    Luo, Jian-Hua; Liu, Silvia; Zuo, Ze-Hua; Chen, Rui; Tseng, George C; Yu, Yan P

    2015-07-01

    Fusion transcript formation is one of the fundamental mechanisms that drives the development of prostate cancer. Because of the advance of high-throughput parallel sequencing, many fusion transcripts have been discovered. However, the discovery rate of fusion transcripts specific for prostate cancer is lagging behind the discoveries made on chromosome abnormalities of prostate cancer. Recent analyses suggest that many fusion transcripts are present in both benign and cancerous tissues. Some of these fusion transcripts likely represent important components of normal gene expression in cells. It is necessary to identify the criteria and features of fusion transcripts that are specific for cancer. In this review, we discuss optimization of RNA sequencing depth for fusion transcript discovery and the characteristics of fusion transcripts in normal prostate tissues and prostate cancer. We also propose a new classification of cancer-specific fusion transcripts on the basis of their tail gene fusion protein product and the roles that these fusions may play in cancer development.

  16. Isolation of cancer stem cells from human prostate cancer samples.

    PubMed

    Vidal, Samuel J; Quinn, S Aidan; de la Iglesia-Vicente, Janis; Bonal, Dennis M; Rodriguez-Bravo, Veronica; Firpo-Betancourt, Adolfo; Cordon-Cardo, Carlos; Domingo-Domenech, Josep

    2014-03-14

    The cancer stem cell (CSC) model has been considerably revisited over the last two decades. During this time CSCs have been identified and directly isolated from human tissues and serially propagated in immunodeficient mice, typically through antibody labeling of subpopulations of cells and fractionation by flow cytometry. However, the unique clinical features of prostate cancer have considerably limited the study of prostate CSCs from fresh human tumor samples. We recently reported the isolation of prostate CSCs directly from human tissues by virtue of their HLA class I (HLAI)-negative phenotype. Prostate cancer cells are harvested from surgical specimens and mechanically dissociated. A cell suspension is generated and labeled with fluorescently conjugated HLAI and stromal antibodies. Subpopulations of HLAI-negative cells are finally isolated using a flow cytometer. The principal limitation of this protocol is the frequently microscopic and multifocal nature of primary cancer in prostatectomy specimens. Nonetheless, isolated live prostate CSCs are suitable for molecular characterization and functional validation by transplantation in immunodeficient mice.

  17. Proteomic analysis of formalin-fixed prostate cancer tissue.

    PubMed

    Hood, Brian L; Darfler, Marlene M; Guiel, Thomas G; Furusato, Bungo; Lucas, David A; Ringeisen, Bradley R; Sesterhenn, Isabell A; Conrads, Thomas P; Veenstra, Timothy D; Krizman, David B

    2005-11-01

    Proteomic analysis of formalin-fixed paraffin-embedded (FFPE) tissue would enable retrospective biomarker investigations of this vast archive of pathologically characterized clinical samples that exist worldwide. These FFPE tissues are, however, refractory to proteomic investigations utilizing many state of the art methodologies largely due to the high level of covalently cross-linked proteins arising from formalin fixation. A novel tissue microdissection technique has been developed and combined with a method to extract soluble peptides directly from FFPE tissue for mass spectral analysis of prostate cancer (PCa) and benign prostate hyperplasia (BPH). Hundreds of proteins from PCa and BPH tissue were identified, including several known PCa markers such as prostate-specific antigen, prostatic acid phosphatase, and macrophage inhibitory cytokine-1. Quantitative proteomic profiling utilizing stable isotope labeling confirmed similar expression levels of prostate-specific antigen and prostatic acid phosphatase in BPH and PCa cells, whereas the expression of macrophage inhibitory cytokine-1 was found to be greater in PCa as compared with BPH cells.

  18. Quantitative characterization of viscoelastic properties of human prostate correlated with histology.

    PubMed

    Zhang, Man; Nigwekar, Priya; Castaneda, Benjamin; Hoyt, Kenneth; Joseph, Jean V; di Sant'Agnese, Anthony; Messing, Edward M; Strang, John G; Rubens, Deborah J; Parker, Kevin J

    2008-07-01

    Quantification of mechanical properties of human prostate tissue is important for developing sonoelastography for prostate cancer detection. In this study, we characterized the frequency-dependent complex Young's modulus of normal and cancerous prostate tissues in vitro by using stress relaxation testing and viscoelastic tissue modeling methods. After radical prostatectomy, small cylindrical tissue samples were acquired in the posterior region of each prostate. A total of 17 samples from eight human prostates were obtained and tested. Stress relaxation tests on prostate samples produced repeatable results that fit a viscoelastic Kelvin-Voigt fractional derivative (KVFD) model (r(2)>0.97). For normal (n = 8) and cancerous (n = 9) prostate samples, the average magnitudes of the complex Young's moduli (|E*|) were 15.9 +/- 5.9 kPa and 40.4 +/- 15.7 kPa at 150 Hz, respectively, giving an elastic contrast of 2.6:1. Nine two-sample t-tests indicated that there are significant differences between stiffness of normal and cancerous prostate tissues in the same gland (p < 0.01). This study contributes to the current limited knowledge on the viscoelastic properties of the human prostate, and the inherent elastic contrast produced by cancer.

  19. Actions of estrogens and endocrine disrupting chemicals on human prostate stem/progenitor cells and prostate cancer risk.

    PubMed

    Hu, Wen-Yang; Shi, Guang-Bin; Hu, Dan-Ping; Nelles, Jason L; Prins, Gail S

    2012-05-06

    Estrogen reprogramming of the prostate gland as a function of developmental exposures (aka developmental estrogenization) results in permanent alterations in structure and gene expression that lead to an increased incidence of prostatic lesions with aging. Endocrine disrupting chemicals (EDCs) with estrogenic activity have been similarly linked to an increased prostate cancer risk. Since it has been suggested that stem cells and cancer stem cells are potential targets of cancer initiation and disease management, it is highly possible that estrogens and EDCs influence the development and progression of prostate cancer through reprogramming and transforming the prostate stem and early stage progenitor cells. In this article, we review recent literature highlighting the effects of estrogens and EDCs on prostate cancer risk and discuss recent advances in prostate stem/progenitor cell research. Our laboratory has recently developed a novel prostasphere model using normal human prostate stem/progenitor cells and established that these cells express estrogen receptors (ERs) and are direct targets of estrogen action. Further, using a chimeric in vivo prostate model derived from these normal human prostate progenitor cells, we demonstrated for the first time that estrogens initiate and promote prostatic carcinogenesis in an androgen-supported environment. We herein discuss these findings and highlight new evidence using our in vitro human prostasphere assay for perturbations in human prostate stem cell self-renewal and differentiation by natural steroids as well as EDCs. These findings support the hypothesis that tissue stem cells may be direct EDC targets which may underlie life-long reprogramming as a consequence of developmental and/or transient adult exposures.

  20. Prostatitis

    PubMed Central

    Domingue, Gerald J.; Hellstrom, Wayne J. G.

    1998-01-01

    The laboratory diagnosis of acute bacterial prostatitis is straightforward and easily accomplished in clinical laboratories. Chronic bacterial prostatitis, and especially chronic idiopathic prostatitis (most often referred to as abacterial prostatitis), presents a real challenge to the clinician and clinical microbiologist. Clinically, the diagnosis of chronic idiopathic prostatitis is differentiated from that of acute prostatitis by a lack of prostatic inflammation and no “significant” (controversial) leukocytes or bacteria in the expressed prostatic secretions. Despite these diagnostic criteria, the etiology of chronic idiopathic prostatitis is unknown. While this review covers the entire spectrum of microbially caused acute prostatitis (including common and uncommon bacteria, viruses, fungi, and parasites) and microbially associated chronic prostatitis, a special focus has been given to chronic idiopathic prostatitis. The idiopathic syndrome is commonly diagnosed in men but is poorly treated. Recent data convincingly suggests a possible bacterial etiology for the condition. Provocative molecular studies have been published reporting the presence of 16S rRNA bacterial sequences in prostate biopsy tissue that is negative for ordinary bacteria by routine culture in men with chronic idiopathic prostatitis. Additionally, special culture methods have indicated that difficult-to-culture coryneforms and coagulase-negative staphylococci are present in expressed prostatic secretions found to be negative by routine culture techniques. Treatment failures are not uncommon in chronic prostatitis. Literature reports suggest that antimicrobial treatment failures in chronic idiopathic prostatitis caused by organisms producing extracellular slime might result from the virulent properties of coagulase-negative staphylococci or other bacteria. While it is difficult to definitively extrapolate from animal models, antibiotic pharmokinetic studies with a murine model have

  1. Reduced expression of NGEP is associated with high-grade prostate cancers: a tissue microarray analysis.

    PubMed

    Mohsenzadegan, Monireh; Madjd, Zahra; Asgari, Mojgan; Abolhasani, Maryam; Shekarabi, Mehdi; Taeb, Jaleh; Shariftabrizi, Ahmad

    2013-10-01

    New gene expressed in prostate (NGEP) is a newly diagnosed prostate-specific gene that is expressed only in normal prostate and prostate cancer cells. Discovery of tissue-specific markers may promote the development of novel targets for immunotherapy of prostate cancer. In the present study, the staining pattern and clinical significance of NGEP were evaluated in a series of prostate tissues composed of 123 prostate cancer, 19 high-grade prostatic intraepithelial neoplasia and 44 samples of benign prostate tissue included in tissue microarrays using immunohistochemistry. Our study demonstrated that NGEP localized mainly in the apical and lateral membranes and was also partially distributed in the cytoplasm of epithelial cells of normal prostate tissue. All of the examined prostate tissues expressed NGEP with a variety of intensities; the level of expression was significantly more in the benign prostate tissues compared to malignant prostate samples (P value <0.001). Among prostate adenocarcinoma samples, a significant and inverse correlation was observed between the intensity of NGEP expression and increased Gleason score (P = 0.007). Taken together, we found that NGEP protein is widely expressed in low-grade to high-grade prostate adenocarcinomas as well as benign prostate tissues, and the intensity of expression is inversely proportional to the level of malignancy. NGEP could be an attractive target for immune-based therapy of prostate cancer patients as an alternative to the conventional therapies particularly in indolent patients.

  2. Evaluating the Anticancer Properties of Liposomal Copper in a Nude Mouse Xenograft Model of Human Prostate Cancer: Formulation, In Vitro, In Vivo, Histology and Tissue Distribution Studies

    PubMed Central

    Wang, Yan; Zeng, San; Lin, Tien-Min; Krugner-Higby, Lisa; Lyman, Doug; Steffen, Dana; Xiong, May P.

    2014-01-01

    Purpose Although copper (Cu) complexes have been investigated as anticancer agents, there has been no description of Cu itself as a cancer killing agent. A stealth liposomal Cu formulation (LpCu) was studied in vitro and in vivo. Methods LpCu was evaluated in prostate cancer origin PC-3 cells by a metabolic cytotoxicity assay, by monitoring reactive oxygen species (ROS), and by flow cytometry. LpCu efficacy was evaluated in vivo using intratumoral and intravenous injections into mice bearing PC-3 xenograft tumors. Toxicology was assessed by performing hematological and blood biochemistry assays, and tissue histology and Cu distribution was investigated by elemental analysis. Results LpCu and free Cu salts displayed similar levels of cell metabolic toxicity and ROS. Flow cytometry indicated that the mechanisms of cell death were both apoptosis and necrosis. Animals injected i.t. with 3.5 mg/kg or i.v. with 3.5 and 7.0 mg/kg LpCu exhibited significant tumor growth inhibition. Kidney and eye were the main organs affected by Cu-mediated toxicities, but spleen and liver were the major organs of Cu deposition. Conclusions LpCu was effective at reducing tumor burden in the xenograft prostate cancer model. There was histological evidence of Cu toxicity in kidneys and eyes of animals treated at the maximum tolerated dose of LpCu 7.0 mg/kg. PMID:24848339

  3. Computer-Aided Detection of Prostate Cancer on Tissue Sections

    PubMed Central

    Peng, Yahui; Jiang, Yulei; Chuang, Shang-Tian; Yang, Ximing J.

    2009-01-01

    We report an automated computer technique for detection of prostate cancer in prostate tissue sections processed with immunohistochemistry. Two sets of color optical images were acquired from prostate tissue sections stained with a double-chromogen triple-antibody cocktail combining alpha-methylacyl-CoA racemase (AMACR), p63, and high-molecular-weight cytokeratin (HMWCK). The first set of images consisted of 20 training images (10 malignant) used for developing the computer technique and 15 test images (7 malignant) used for testing and optimizing the technique. The second set of images consisted of 299 images (114 malignant) used for evaluation of the performance of the computer technique. The computer technique identified image segments of AMACR-labeled malignant epithelial cells (red), p63-and HMWCK-labeled benign basal cells (brown), and secretory and stromal cells (blue) for identifying prostate cancer automatically. The sensitivity and specificity of the computer technique were 94% (16/17) and 94% (17/18), respectively, on the first (training and test) set of images, and 88% (79/90) and 97% (136/140), respectively, on the second (validation) set of images. If high-grade prostatic intraepithelial neoplasia (HGPIN), which is a precursor of cancer, and atypical cases were included, the sensitivity and specificity were 85% (97/114) and 89% (165/185), respectively. These results show that the novel automated computer technique can accurately identify prostatic adenocarcinoma in the triple-antibody cocktail-stained prostate sections. PMID:19417626

  4. Influence of zinc deficiency on AKT-MDM2-P53 signaling axes in normal and malignant human prostate cells

    USDA-ARS?s Scientific Manuscript database

    With prostate being the highest zinc-accumulating tissue before the onset of cancer, the effects of physiologic levels of zinc on Akt-Mdm2-p53 and Akt-p21 signaling axes in human normal prostate epithelial cells (PrEC) and malignant prostate LNCaP cells were examined. Cells were cultured for 6 d in...

  5. Differentially expressed androgen-regulated genes in androgen-sensitive tissues reveal potential biomarkers of early prostate cancer.

    PubMed

    Altintas, Dogus Murat; Allioli, Nathalie; Decaussin, Myriam; de Bernard, Simon; Ruffion, Alain; Samarut, Jacques; Vlaeminck-Guillem, Virginie

    2013-01-01

    Several data favor androgen receptor implication in prostate cancer initiation through the induction of several gene activation programs. The aim of the study is to identify potential biomarkers for early diagnosis of prostate cancer (PCa) among androgen-regulated genes (ARG) and to evaluate comparative expression of these genes in normal prostate and normal prostate-related androgen-sensitive tissues that do not (or rarely) give rise to cancer. ARG were selected in non-neoplastic adult human prostatic epithelial RWPE-1 cells stably expressing an exogenous human androgen receptor, using RNA-microarrays and validation by qRT-PCR. Expression of 48 preselected genes was quantified in tissue samples (seminal vesicles, prostate transitional zones and prostate cancers, benign prostatic hypertrophy obtained from surgical specimens) using TaqMan® low-density arrays. The diagnostic performances of these potential biomarkers were compared to that of genes known to be associated with PCa (i.e. PCA3 and DLX1). By crossing expression studies in 26 matched PCa and normal prostate transitional zone samples, and 35 matched seminal vesicle and PCa samples, 14 genes were identified. Similarly, 9 genes were overexpressed in 15 benign prostatic hypertrophy samples, as compared to PCa samples. Overall, we selected 8 genes of interest to evaluate their diagnostic performances in comparison with that of PCA3 and DLX1. Among them, 3 genes: CRYAB, KCNMA1 and SDPR, were overexpressed in all 3 reference non-cancerous tissues. The areas under ROC curves of these genes reached those of PCA3 (0.91) and DLX1 (0.94). We identified ARG with reduced expression in PCa and with significant diagnostic values for discriminating between cancerous and non-cancerous prostatic tissues, similar that of PCA3. Given their expression pattern, they could be considered as potentially protective against prostate cancer. Moreover, they could be complementary to known genes overexpressed in PCa and included along

  6. Localization of angiotensin-converting enzyme in the human prostate: pathological expression in benign prostatic hyperplasia.

    PubMed

    Nassis, L; Frauman, A G; Ohishi, M; Zhuo, J; Casley, D J; Johnston, C I; Fabiani, M E

    2001-12-01

    Benign prostatic hyperplasia (BPH) is the most common hyperplastic disease in man and it is characterized by increased cellular growth (stromal and epithelial hyperplasia) and enhanced local sympathetic tone, both of which are known to be augmented by activation of the renin-angiotensin system (RAS) in other tissues. Angiotensin-converting enzyme (ACE) is an integral component of the RAS that is responsible for the production of the active peptide angiotensin II from the inactive precursor angiotensin I. The present study was undertaken to map the anatomical localization of ACE protein and messenger ribonucleic acid (mRNA) in the normal human prostate and to establish whether their expression is pathologically altered in BPH. Human prostate samples were obtained at post-mortem and histologically defined as normal or hyperplastic. ACE protein binding/expression was determined by in vitro autoradiography and immunohistochemistry using the ACE-specific radioligand [125I]-MK351A and a mouse anti-ACE polyclonal antibody, respectively, whereas the spatiotemporal distribution of ACE mRNA was determined by in situ hybridization using 35S-labelled oligonucleotide probes. ACE protein was localized to the glandular epithelium in the human prostate. ACE binding and immunostaining were increased in BPH compared with normal (non-hyperplastic) prostate specimens [X-ray film autoradiography: normal 873+/-48 dpm/mm2 (n=8) vs. BPH 1631+/-274 dpm/mm2 (n=6), p<0.05; emulsion autoradiography: normal 3.1+/-0.5 grains/mm2 (n=6) vs. BPH 32.8+/-8.6 grains/mm2 (n=5), p<0.01]. ACE mRNA was also localized to glandular epithelial cells in the human prostate with a significant increase in ACE mRNA expression in BPH compared with the normal prostate [normal 11.04+/-2.03 grains/cell (n=220 cells total) vs. BPH 22.29+/-1.34 grains/cell (n=198 cells total), p<0.05]. The findings of the present study suggest that ACE is localized to the glandular epithelium of the human prostate and that its

  7. Differential expression of human leukocyte antigen-G (HLA-G) messenger RNAs and proteins in normal human prostate and prostatic adenocarcinoma.

    PubMed

    Langat, Daudi K; Sue Platt, J; Tawfik, Ossama; Fazleabas, Asgerally T; Hunt, Joan S

    2006-08-01

    Human leukocyte antigen-G (HLA-G) is a major histocompatibility complex class Ib gene expressed in normal organs and in some tumors. The glycoproteins encoded by this gene are best known for their immunosuppressive properties. Because isoform-specific expression of HLA-G in male reproductive organs has not been reported, we investigated HLA-G1, -G2, -G5, -G6 mRNAs and proteins in four-to-five samples of normal prostate glands, prostates with benign prostatic hyperplasia and prostate adenocarcinomas using RT-PCR and immunohistochemistry. All tissues contained HLA-G1, -G2, -G5 and -G6 specific mRNAs, but only HLA-G5 protein was detectable. In normal prostate glands, HLA-G5 protein was prominent in the cytoplasm of tubuloglandular epithelia and in glandular secretions. Staining was reduced in samples of benign prostatic hyperplasia but remained localized to the cytoplasm of glandular epithelia and secretions. In prostatic adenocarcinomas, HLA-G5 protein was detectable mainly in the secretions. Thus, HLA-G5 but not HLA-G1, -G2 or -G6 is produced in the normal prostate and is present in prostatic secretions. In addition, normal cellular localization is disturbed in benign and malignant prostatic adenocarcinomas. The results are consistent with this molecule may influencing female immune receptivity to sperm and suggest that such immunosuppression could be disturbed in men with prostatic adenocarcinomas.

  8. Extracellular Vesicles from Metastatic Rat Prostate Tumors Prime the Normal Prostate Tissue to Facilitate Tumor Growth

    PubMed Central

    Halin Bergström, Sofia; Hägglöf, Christina; Thysell, Elin; Bergh, Anders; Wikström, Pernilla; Lundholm, Marie

    2016-01-01

    Accumulating data indicates that tumor-derived extracellular vesicles (EVs) are responsible for tumor-promoting effects. However, if tumor EVs also prepare the tumor-bearing organ for subsequent tumor growth, and if this effect is different in low and high malignant tumors is not thoroughly explored. Here we used orthotopic rat Dunning R-3327 prostate tumors to compare the role of EVs from fast growing and metastatic MatLyLu (MLL) tumors with EVs from more indolent and non-metastatic Dunning G (G) tumors. Prostate tissue pre-conditioned with MLL-EVs in vivo facilitated G tumor establishment compared to G-EVs. MLL-EVs increased prostate epithelial proliferation and macrophage infiltration into the prostate compared to G-EVs. Both types of EVs increased macrophage endocytosis and the mRNA expression of genes associated with M2 polarization in vitro, with MLL-EVs giving the most pronounced effects. MLL-EVs also altered the mRNA expression of growth factors and cytokines in primary rat prostate fibroblasts compared to G-EVs, suggesting fibroblast activation. Our findings propose that EVs from metastatic tumors have the ability to prime the prostate tissue and enhance tumor growth to a higher extent than EVs from non-metastatic tumors. Identifying these differences could lead to novel therapeutic targets and potential prognostic markers for prostate cancer. PMID:27550147

  9. Keratin 13 expression reprograms bone and brain metastases of human prostate cancer cells

    PubMed Central

    Jones, Lawrence W.; Chu, Gina C-Y; Wu, Jason B-Y.; Huang, Jen-Ming; Li, Quanlin; You, Sungyong; Kim, Jayoung; Lu, Yi-Tsung; Mrdenovic, Stefan; Wang, Ruoxiang; Freeman, Michael R.; Garraway, Isla; Lewis, Michael S.; Chung, Leland W. K.; Zhau, Haiyen E.

    2016-01-01

    Lethal progression of prostate cancer metastasis can be improved by developing animal models that recapitulate the clinical conditions. We report here that cytokeratin 13 (KRT13), an intermediate filament protein, plays a directive role in prostate cancer bone, brain, and soft tissue metastases. KRT13 expression was elevated in bone, brain, and soft tissue metastatic prostate cancer cell lines and in primary and metastatic clinical prostate, lung, and breast cancer specimens. When KRT13 expression was determined at a single cell level in primary tumor tissues of 44 prostate cancer cases, KRT13 level predicted bone metastasis and the overall survival of prostate cancer patients. Genetically enforced KRT13 expression in human prostate cancer cell lines drove metastases toward mouse bone, brain and soft tissues through a RANKL-independent mechanism, as KRT13 altered the expression of genes associated with EMT, stemness, neuroendocrine/neuromimicry, osteomimicry, development, and extracellular matrices, but not receptor activator NF-κB ligand (RANKL) signaling networks in prostate cancer cells. Our results suggest new inhibitors targeting RANKL-independent pathways should be developed for the treatment of prostate cancer bone and soft tissue metastases. PMID:27835867

  10. Androgenic Regulation of White Adipose Tissue-Prostate Cancer Interactions

    DTIC Science & Technology

    2012-05-01

    April 2012 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Androgenic Regulation of White Adipose Tissue -Prostate Cancer Interactions 5b. GRANT NUMBER...Floryk D, Kurosaka S, Tanimoto R, Yang G, Goltsov A, Park S, Thompson TC. Castration- induced changes in mouse epididymal white adipose tissue . Mol Cell...1. Floryk D, Kurosaka S, Tanimoto R, Yang G, Goltsov A, Park S, Thompson TC. Castration- induced changes in mouse epididymal white adipose tissue

  11. Dosimetric effect of tissue heterogeneity for (125)I prostate implants.

    PubMed

    Oliveira, Susana Maria; Teixeira, Nuno José; Fernandes, Lisete; Teles, Pedro; Vaz, Pedro

    2014-11-01

    To use Monte Carlo (MC) together with voxel phantoms to analyze the tissue heterogeneity effect in the dose distributions and equivalent uniform dose (EUD) for (125)I prostate implants. Dose distribution calculations in low dose-rate brachytherapy are based on the dose deposition around a single source in a water phantom. This formalism does not take into account tissue heterogeneities, interseed attenuation, or finite patient dimensions effects. Tissue composition is especially important due to the photoelectric effect. The computed tomographies (CT) of two patients with prostate cancer were used to create voxel phantoms for the MC simulations. An elemental composition and density were assigned to each structure. Densities of the prostate, vesicles, rectum and bladder were determined through the CT electronic densities of 100 patients. The same simulations were performed considering the same phantom as pure water. Results were compared via dose-volume histograms and EUD for the prostate and rectum. The mean absorbed doses presented deviations of 3.3-4.0% for the prostate and of 2.3-4.9% for the rectum, when comparing calculations in water with calculations in the heterogeneous phantom. In the calculations in water, the prostate D 90 was overestimated by 2.8-3.9% and the rectum D 0.1cc resulted in dose differences of 6-8%. The EUD resulted in an overestimation of 3.5-3.7% for the prostate and of 7.7-8.3% for the rectum. The deposited dose was consistently overestimated for the simulation in water. In order to increase the accuracy in the determination of dose distributions, especially around the rectum, the introduction of the model-based algorithms is recommended.

  12. Dosimetric effect of tissue heterogeneity for 125I prostate implants

    PubMed Central

    Oliveira, Susana Maria; Teixeira, Nuno José; Fernandes, Lisete; Teles, Pedro; Vaz, Pedro

    2014-01-01

    Aim To use Monte Carlo (MC) together with voxel phantoms to analyze the tissue heterogeneity effect in the dose distributions and equivalent uniform dose (EUD) for 125I prostate implants. Background Dose distribution calculations in low dose-rate brachytherapy are based on the dose deposition around a single source in a water phantom. This formalism does not take into account tissue heterogeneities, interseed attenuation, or finite patient dimensions effects. Tissue composition is especially important due to the photoelectric effect. Materials and methods The computed tomographies (CT) of two patients with prostate cancer were used to create voxel phantoms for the MC simulations. An elemental composition and density were assigned to each structure. Densities of the prostate, vesicles, rectum and bladder were determined through the CT electronic densities of 100 patients. The same simulations were performed considering the same phantom as pure water. Results were compared via dose–volume histograms and EUD for the prostate and rectum. Results The mean absorbed doses presented deviations of 3.3–4.0% for the prostate and of 2.3–4.9% for the rectum, when comparing calculations in water with calculations in the heterogeneous phantom. In the calculations in water, the prostate D90 was overestimated by 2.8–3.9% and the rectum D0.1cc resulted in dose differences of 6–8%. The EUD resulted in an overestimation of 3.5–3.7% for the prostate and of 7.7–8.3% for the rectum. Conclusions The deposited dose was consistently overestimated for the simulation in water. In order to increase the accuracy in the determination of dose distributions, especially around the rectum, the introduction of the model-based algorithms is recommended. PMID:25337412

  13. ICRAC controls the rapid androgen response in human primary prostate epithelial cells and is altered in prostate cancer

    PubMed Central

    Holzmann, Christian; Kilch, Tatiana; Kappel, Sven; Armbrüster, Andrea; Jung, Volker; Stöckle, Michael; Bogeski, Ivan; Schwarz, Eva C.; Peinelt, Christine

    2013-01-01

    Labelled 5α-dihydrotestosterone (DHT) binding experiments have shown that expression levels of (yet unidentified) membrane androgen receptors (mAR) are elevated in prostate cancer and correlate with a negative prognosis. However, activation of these receptors which mediate a rapid androgen response can counteract several cancer hallmark functions such as unlimited proliferation, enhanced migration, adhesion and invasion and the inability to induce apoptosis. Here, we investigate the downstream signaling pathways of mAR and identify rapid DHT induced activation of store-operated Ca2+ entry (SOCE) in primary cultures of human prostate epithelial cells (hPEC) from non-tumorous tissue. Consequently, down-regulation of Orai1, the main molecular component of Ca2+ release-activated Ca2+ (CRAC) channels results in an almost complete loss of DHT induced SOCE. We demonstrate that this DHT induced Ca2+ influx via Orai1 is important for rapid androgen triggered prostate specific antigen (PSA) release. We furthermore identified alterations of the molecular components of CRAC channels in prostate cancer. Three lines of evidence indicate that prostate cancer cells down-regulate expression of the Orai1 homolog Orai3: First, Orai3 mRNA expression levels are significantly reduced in tumorous tissue when compared to non-tumorous tissue from prostate cancer patients. Second, mRNA expression levels of Orai3 are decreased in prostate cancer cell lines LNCaP and DU145 when compared to hPEC from healthy tissue. Third, the pharmacological profile of CRAC channels in prostate cancer cell lines and hPEC differ and siRNA based knock-down experiments indicate changed Orai3 levels are underlying the altered pharmacological profile. The cancer-specific composition and pharmacology of CRAC channels identifies CRAC channels as putative targets in prostate cancer therapy. PMID:24240085

  14. Parthenolide Selectively Sensitizes Prostate Tumor Tissue to Radiotherapy while Protecting Healthy Tissues In Vivo.

    PubMed

    Morel, Katherine L; Ormsby, Rebecca J; Bezak, Eva; Sweeney, Christopher J; Sykes, Pamela J

    2017-05-01

    Radiotherapy is widely used in cancer treatment, however the benefits can be limited by radiation-induced damage to neighboring normal tissues. Parthenolide (PTL) exhibits anti-inflammatory and anti-tumor properties and selectively induces radiosensitivity in prostate cancer cell lines, while protecting primary prostate epithelial cell lines from radiation-induced damage. Low doses of radiation have also been shown to protect from subsequent high-dose-radiation-induced apoptosis as well as DNA damage. These properties of PTL and low-dose radiation could be used to improve radiotherapy by killing more tumor cells and less normal cells. Sixteen-week-old male Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) and C57BL/6J mice were treated with PTL (40 mg/kg), dimethylaminoparthenolide (DMAPT, a PTL analogue with increased bioavailability) (100 mg/kg), or vehicle control three times over one week prior to combinations of low (10 mGy) and high (6 Gy) doses of whole-body X-irradiation. Tissues were analyzed for apoptosis at a range of time points up to 72 h postirradiation. Both PTL and DMAPT protected normal tissues, but not prostate tumor tissues, from a significant proportion of high-dose-radiation-induced apoptosis. DMAPT provided superior protection compared to PTL in normal dorsolateral prostate (71.7% reduction, P = 0.026), spleen (48.2% reduction, P = 0.0001) and colorectal tissue (38.0% reduction, P = 0.0002), and doubled radiation-induced apoptosis in TRAMP prostate tumor tissue (101.3% increase, P = 0.039). Both drugs induced the greatest radiosensitivity in TRAMP prostate tissue in areas with higher grade prostatic intraepithelial neoplasia (PIN) lesions. A 10 mGy dose delivered 3 h prior to a 6 Gy dose induced a radioadaptive apoptosis response in normal C57Bl/6J prostate (28.4% reduction, P = 0.045) and normal TRAMP spleen (13.6% reduction, P = 0.047), however the low-dose-adaptive radioprotection did not significantly add to the PTL

  15. Prostatic penetration of meropenem in humans, and dosage considerations for prostatitis based on a site-specific pharmacokinetic/pharmacodynamic evaluation.

    PubMed

    Nishikawa, Genya; Ikawa, Kazuro; Nakamura, Kogenta; Yamada, Yoshiaki; Zennami, Kenji; Mitsui, Kenji; Narushima, Masahiro; Ikeda, Kayo; Morikawa, Norifumi; Sumitomo, Makoto

    2013-03-01

    The aims of this study were to investigate the penetration of meropenem (MER) into human prostate tissue and to assess MER regimens for prostatitis by performing a site-specific pharmacokinetic/pharmacodynamic evaluation. Patients with prostatic hypertrophy (n=49) prophylactically received a 0.5-h infusion of MER (250 mg or 500 mg) before transurethral resection of the prostate. MER concentrations in plasma (0.5-5h) and prostate tissue (0.5-1.5h) were measured chromatographically. Concentration data were analysed pharmacokinetically with a three-compartment model and were used to estimate the drug exposure time above the minimum inhibitory concentration for bacteria (T>MIC, % of 24h) in prostate tissue, an indicator for antibacterial effects at the site of action. The prostate tissue/plasma ratio was 16.6% for the maximum drug concentration and 17.7% for the area under the drug concentration-time curve, irrespective of the dose. Against MIC distributions for clinical isolates of Escherichia coli, Klebsiella spp. and Proteus spp., 500 mg once daily achieved a >90% probability of attaining the bacteriostatic target (20% T>MIC) in prostate tissue, and 500 mg twice daily achieved a >90% probability of attaining the bactericidal target (40% T>MIC) in prostate tissue. However, against the Pseudomonas aeruginosa isolates, none of the tested regimens achieved a >90% probability of attaining the bacteriostatic or bactericidal targets. Copyright © 2012 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  16. Glutathione transferase isoenzymes from human prostate.

    PubMed Central

    Di Ilio, C; Aceto, A; Bucciarelli, T; Angelucci, S; Felaco, M; Grilli, A; Federici, G

    1990-01-01

    By using affinity-chromatography and isoelectric-focusing techniques, several forms of glutathione transferase (GSTs) were resolved from human prostate cytosol. All the three major classes of GST, i.e. Alpha, Mu and Pi, are present in human prostate. However, large inter-individual variation in the qualitative and quantitative expression of different isoenzymes resulted in the samples investigated. The most abundant group of prostate isoenzymes showed acid (pI 4.3-4.7) behaviour and were classified as Pi class GSTs on the basis of their immunological and structural properties. Immunohistochemical staining of Pi class GSTs was prevalently distributed in the epithelial cells surrounding the alveolar lumen. Class Mu GSTs are also expressed, although in small amounts and in a limited number of samples, by human prostate. The major cationic isoenzyme purified from prostate, GST-9.6; (pI 9.6; apparent subunit molecular mass of 28 kDa), appears to be different from the cationic GST alpha-epsilon forms isolated from human liver and kidney as evidenced by its structural, kinetical and immunological properties. This enzyme, which accounts for about 20-30% (on protein basis) of total amount of GSTs, is expressed by only 40% of samples. GST-9.6 has the ability to cross-react in immunoblotting analysis with antisera raised against rat liver GST 2-2, rather than with antisera raised against members of human Alpha, Mu and Pi class GSTs. Although prostate GST-9.6 shows close relationship with the human skin GST pI 9.9, it does not correspond to any other known human GST. Images Fig. 2. Fig. 3. Fig. 4. PMID:2241927

  17. Selective changes of retroelement expression in human prostate cancer.

    PubMed

    Goering, Wolfgang; Ribarska, Teodora; Schulz, Wolfgang A

    2011-10-01

    Retroelements constitute a large part of the human genome. These sequences are mostly silenced in normal cells, but genome-wide DNA hypomethylation in cancers might lead to their re-expression. Whether this re-expression really occurs in human cancers is largely unkown. We therefore investigated expression and DNA methylation of several classes of retroelements in human prostate cancer tissues and cell lines by quantitative reverse transcription-polymerase chain reaction and pyrosequencing, respectively. The most striking finding was strong and generalized increased expression of the HERV-K_22q11.23 provirus in cancers, including de novo expression of a spliced accessory Np9 transcript in some tumors. In parallel, DNA methylation in the long terminal repeat (LTR) decreased. Conversely, HERVK17 expression was significantly diminished in cancer tissues, but this decrease was unrelated to LTR methylation. Expression of both proviruses was restricted to androgen-responsive prostate cancer cell lines and LTRs sequences containing steroid hormone-responsive elements bound the androgen receptor and conferred androgen responsiveness to reporter constructs. Expression of LINE-1 5'-untranslated region (UTR) and 3'-UTR sequences in prostate cancers rather decreased, despite significant hypomethylation of the internal LINE-1 promoter. Increased expression of the young AluYa5 and AluYb8 families was restricted to individual tumors. Our findings demonstrate a surprising specificity of changes in expression and DNA methylation of retroelements in prostate cancer. In particular, LINE-1 hypomethylation does not lead to generalized overexpression, but specific human endogenous retrovirus-K proviruses display conspicuous changes in their expression hinting at significant functions during prostate carcinogenesis.

  18. Estradiol suppresses tissue androgens and prostate cancer growth in castration resistant prostate cancer

    PubMed Central

    2010-01-01

    Background Estrogens suppress tumor growth in prostate cancer which progresses despite anorchid serum androgen levels, termed castration resistant prostate cancers (CRPC), although the mechanisms are unclear. We hypothesize that estrogen inhibits CRPC in anorchid animals by suppressing tumoral androgens, an effect independent of the estrogen receptor. Methods The human CRPC xenograft LuCaP 35V was implanted into orchiectomized male SCID mice and established tumors were treated with placebo, 17β-estradiol or 17β-estradiol and estrogen receptor antagonist ICI 182,780. Effects of 17β-estradiol on tumor growth were evaluated and tissue testosterone (T) and dihydrotestosterone (DHT) evaluated by mass spectrometry. Results Treatment of LuCaP 35V with 17β-estradiol slowed tumor growth compared to controls (tumor volume at day 21: 785 ± 81 mm3 vs. 1195 ± 84 mm3, p = 0.002). Survival was also significantly improved in animals treated with 17β-estradiol (p = 0.03). The addition of the estrogen receptor antagonist ICI 182,780 did not significantly change survival or growth. 17β-estradiol in the presence and absence of ICI 182,780 suppressed tumor testosterone (T) and dihydrotestosterone (DHT) as assayed by mass spectrometry. Tissue androgens in placebo treated LuCaP 35V xenografts were; T = 0.71 ± 0.28 pg/mg and DHT = 1.73 ± 0.36 pg/mg. In 17β-estradiol treated LuCaP35V xenografts the tissue androgens were, T = 0.20 ± 0.10 pg/mg and DHT = 0.15 ± 0.15 pg/mg, (p < 0.001 vs. controls). Levels of T and DHT in control liver tissue were < 0.2 pg/mg. Conclusions CRPC in anorchid animals maintains tumoral androgen levels despite castration. 17β-estradiol significantly suppressed tumor T and DHT and inhibits growth of CRPC in an estrogen receptor independent manner. The ability to manipulate tumoral androgens will be critical in the development and testing of agents targeting CRPC through tissue steroidogenesis. PMID:20509933

  19. Indentation loading response of a resonance sensor--discriminating prostate cancer and normal tissue.

    PubMed

    Jalkanen, Ville; Andersson, Britt M; Bergh, Anders; Ljungberg, Börje; Lindahl, Olof A

    2013-10-01

    Prostate cancer is the most common type of cancer among men worldwide. Mechanical properties of prostate tissue are promising for distinguishing prostate cancer from healthy prostate tissue. The aim was to investigate the indentation loading response of a resonance sensor for discriminating prostate cancer tissue from normal tissue. Indentation measurements were done on prostate tissue specimens ex vivo from 10 patients from radical prostatectomy. The measurement areas were analysed using standard histological methods. The stiffness parameter was linearly dependent on the loading force (average R(2 )= 0.90) and an increased loading force caused a greater stiffness contrast of prostate cancer vs normal tissue. The accuracy of the stiffness contrast was assessed by the ROC curve with the area under the curve being 0.941 for a loading force of 12.8 mN. The results are promising for the development of a resonance sensor instrument for detecting prostate cancer.

  20. Association and regulation of protein factors of field effect in prostate tissues

    PubMed Central

    Gabriel, Kristin N.; Jones, Anna C.; Nguyen, Julie P.T.; Antillon, Kresta S.; Janos, Sara N.; Overton, Heidi N.; Jenkins, Shannon M.; Frisch, Emily H.; Trujillo, Kristina A.; Bisoffi, Marco

    2016-01-01

    Field effect or field cancerization denotes the presence of molecular aberrations in structurally intact cells residing in histologically normal tissues adjacent to solid tumors. Currently, the etiology of prostate field-effect formation is unknown and there is a prominent lack of knowledge of the underlying cellular and molecular pathways. We have previously identified an upregulated expression of several protein factors representative of prostate field effect, i.e., early growth response-1 (EGR-1), platelet-derived growth factor-A (PDGF-A), macrophage inhibitory cytokine-1 (MIC-1), and fatty acid synthase (FASN) in tissues at a distance of 1 cm from the visible margin of intracapsule prostate adenocarcinomas. We have hypothesized that the transcription factor EGR-1 could be a key regulator of prostate field-effect formation by controlling the expression of PDGF-A, MIC-1, and FASN. Taking advantage of our extensive quantitative immunofluorescence data specific for EGR-1, PDGF-A, MIC-1, and FASN generated in disease-free, tumor-adjacent, and cancerous human prostate tissues, we chose comprehensive correlation as our major approach to test this hypothesis. Despite the static nature and sample heterogeneity of association studies, we show here that sophisticated data generation, such as by spectral image acquisition, linear unmixing, and digital quantitative imaging, can provide meaningful indications of molecular regulations in a physiologically relevant in situ environment. Our data suggest that EGR-1 acts as a key regulator of prostate field effect through induction of pro-proliferative (PDGF-A and FASN), and suppression of pro-apoptotic (MIC-1) factors. These findings were corroborated by computational promoter analyses and cell transfection experiments in non-cancerous prostate epithelial cells with ectopically induced and suppressed EGR-1 expression. Among several clinical applications, a detailed knowledge of pathways of field effect may lead to the

  1. Association of prostate cancer risk variants with gene expression in normal and tumor tissue.

    PubMed

    Penney, Kathryn L; Sinnott, Jennifer A; Tyekucheva, Svitlana; Gerke, Travis; Shui, Irene M; Kraft, Peter; Sesso, Howard D; Freedman, Matthew L; Loda, Massimo; Mucci, Lorelei A; Stampfer, Meir J

    2015-01-01

    Numerous germline genetic variants are associated with prostate cancer risk, but their biologic role is not well understood. One possibility is that these variants influence gene expression in prostate tissue. We therefore examined the association of prostate cancer risk variants with the expression of genes nearby and genome-wide. We generated mRNA expression data for 20,254 genes with the Affymetrix GeneChip Human Gene 1.0 ST microarray from normal prostate (N = 160) and prostate tumor (N = 264) tissue from participants of the Physicians' Health Study and Health Professionals Follow-up Study. With linear models, we tested the association of 39 risk variants with nearby genes and all genes, and the association of each variant with canonical pathways using a global test. In addition to confirming previously reported associations, we detected several new significant (P < 0.05) associations of variants with the expression of nearby genes including C2orf43, ITGA6, MLPH, CHMP2B, BMPR1B, and MTL5. Genome-wide, five genes (MSMB, NUDT11, RBPMS2, NEFM, and KLHL33) were significantly associated after accounting for multiple comparisons for each SNP (P < 2.5 × 10(-6)). Many more genes had an FDR <10%, including SRD5A1 and PSCA, and we observed significant associations with pathways in tumor tissue. The risk variants were associated with several genes, including promising prostate cancer candidates and lipid metabolism pathways, suggesting mechanisms for their impact on disease. These genes should be further explored in biologic and epidemiologic studies. Determining the biologic role of these variants can lead to improved understanding of prostate cancer etiology and identify new targets for chemoprevention. ©2014 American Association for Cancer Research.

  2. Expression of prostate stem cell antigen (PSCA) in prostate cancer: a tissue microarray study of Iranian patients.

    PubMed

    Taeb, Jaleh; Asgari, Mojgan; Abolhasani, Maryam; Farajollahi, Mohammad M; Madjd, Zahra

    2014-01-01

    Proteins expressed in prostate cancer, including prostate stem cell antigen (PSCA), have been investigated as biomarkers for diagnosis and therapy of prostate cancer. Immunohistochemical analysis of PSCA expression was performed on tissue microarrays of 185 paraffin-embedded tissues of Iranian patients, including 114 prostate cancers (PCa), 21 High Grade Prostatic Intraepithelial Neoplasias (HGPIN) and 50 samples of benign prostate tissue. The level of PSCA expression was compared between benign tissues, HGPIN and PCa. Then the correlations of PSCA expression with clinicopathologic parameters were assessed in PCa. The PSCA expression was detected in the membrane and cytoplasm of epithelial secretory cells in normal prostate tissues, HGPIN and PCa with a variety of intensities. The intensity of PSCA staining was significantly increased in the PCa group as compared with HGPIN and benign prostate tissues (P-value<0.05). Moreover, the level of PSCA expression was increased with higher Gleason score of PCa (P-value=0.036). The data presented here revealed that expression of PSCA as a cell surface marker increased from benign prostate tissues (BPH) and HGPIN to PCa, and its expression in PCa was positively associated with poor cell differentiation, suggesting that PSCA could be considered as a valuable target for diagnosis and therapy of PCa. Copyright © 2013 Elsevier GmbH. All rights reserved.

  3. Inflammation in Benign Prostate Tissue and Prostate Cancer in the Finasteride Arm of the Prostate Cancer Prevention Trial.

    PubMed

    Murtola, Teemu J; Gurel, Bora; Umbehr, Martin; Lucia, M Scott; Thompson, Ian M; Goodman, Phyllis J; Kristal, Alan R; Parnes, Howard L; Lippman, Scott M; Sutcliffe, Siobhan; Peskoe, Sarah B; Barber, John R; Drake, Charles G; Nelson, William G; De Marzo, Angelo M; Platz, Elizabeth A

    2016-03-01

    A previous analysis of the placebo arm of the Prostate Cancer Prevention Trial (PCPT) reported 82% overall prevalence of intraprostatic inflammation and identified a link between inflammation and higher-grade prostate cancer and serum PSA. Here, we studied these associations in the PCPT finasteride arm. Prostate cancer cases (N = 197) detected either on a clinically indicated biopsy or on protocol-directed end-of-study biopsy, and frequency-matched controls (N = 248) with no cancer on an end-of-study biopsy were sampled from the finasteride arm. Inflammation in benign prostate tissue was visually assessed using digital images of hematoxylin and eosin-stained sections. Logistic regression was used for statistical analysis. In the finasteride arm, 91.6% of prostate cancer cases and 92.4% of controls had at least one biopsy core with inflammation in benign areas (P < 0.001 for difference compared with placebo arm). Overall, the odds of prostate cancer did not differ by prevalence [OR, 0.90; 95% confidence interval (CI), 0.44-1.84] or extent (P trend = 0.68) of inflammation. Inflammation was not associated with higher-grade disease (prevalence: OR, 1.07; 95% CI, 0.43-2.69). Furthermore, mean PSA concentration did not differ by the prevalence or extent of inflammation in either cases or controls. The prevalence of intraprostatic inflammation was higher in the finasteride than placebo arm of the PCPT, with no association with higher-grade prostate cancer. Finasteride may attenuate the association between inflammation and higher-grade prostate cancer. Moreover, the missing link between intraprostatic inflammation and PSA suggests that finasteride may reduce inflammation-associated PSA elevation. ©2015 American Association for Cancer Research.

  4. Inflammation in benign prostate tissue and prostate cancer in the finasteride arm of the Prostate Cancer Prevention Trial*

    PubMed Central

    Murtola, Teemu J.; Gurel, Bora; Umbehr, Martin; Lucia, M. Scott; Thompson, Ian M.; Goodman, Phyllis J.; Kristal, Alan R.; Parnes, Howard L.; Lippman, Scott M.; Sutcliffe, Siobhan; Peskoe, Sarah B.; Barber, John R.; Drake, Charles G.; Nelson, William G.; De Marzo, Angelo M.; Platz, Elizabeth A.

    2015-01-01

    Background A previous analysis of the placebo arm of the Prostate Cancer Prevention Trial (PCPT) reported 82% overall prevalence of intraprostatic inflammation and identified a link between inflammation and higher-grade prostate cancer and serum PSA. Here we studied these associations in the PCPT finasteride arm. Methods Prostate cancer cases (N=197) detected either on a clinically indicated biopsy or on protocol-directed end-of-study biopsy, and frequency-matched controls (N=248) with no cancer on an end-of-study biopsy were sampled from the finasteride arm. Inflammation in benign prostate tissue was visually assessed using digital images of H&E stained sections. Logistic regression was used for statistical analysis. Results In the finasteride arm, 91.6% of prostate cancer cases and 92.4% of controls had at least one biopsy core with inflammation in benign areas; p < 0.001 for difference compared to placebo arm. Overall, the odds of prostate cancer did not differ by prevalence (OR=0.90, 95% CI 0.44-1.84) or extent (P-trend=0.68) of inflammation. Inflammation was not associated with higher-grade disease (prevalence: OR=1.07, 95% CI 0.43-2.69). Furthermore, mean PSA concentration did not differ by the prevalence or extent of inflammationin either cases or controls. Conclusion The prevalence of intraprostatic inflammation was higher in the finasteride than placebo arm of the PCPT, with no association with higher-grade prostate cancer. Impact Finasteride may attenuate the association between inflammation and higher-grade prostate cancer. Moreover, the missing link between intraprostatic inflammation and PSA suggests that finasteride may reduce inflammation-associated PSA elevation. PMID:26715424

  5. Immunohistochemistry of the cytoskeleton of human prostatic epithelium. Evidence for disturbed organization in neoplasia.

    PubMed Central

    Purnell, D. M.; Heatfield, B. M.; Anthony, R. L.; Trump, B. F.

    1987-01-01

    An indirect immunoperoxidase technique was used to evaluate keratin, actin, tubulin, and calmodulin immunoreactivity in histologic sections of normal, hyperplastic, and neoplastic human prostate. Polyclonal as well as monoclonal keratin antibodies produced equivalent and intense staining of normal epithelium. The immunoreactivity of normal prostate with keratin antibodies was more pronounced than with antibodies to the other components of the cytoskeleton. Variation in staining for components of the cytoskeleton was minimal. The same findings applied to hyperplastic prostate. The immunoreactivity of prostate tumors with antibodies to these cytoskeletal proteins differed markedly from normal prostate. Prostatic carcinomas showed reduced keratin immunoreactivity with a panepithelial antibody, but unaltered or enhanced immunoreactivity with tubulin, actin, and calmodulin antibodies. Many tumors were unreactive with a monoclonal keratin antibody that was strongly reactive with tissues that contained cytokeratin 18 (45-kd) and which intensely stained normal and hyperplastic prostate. In addition, prostate carcinomas often yielded heterogeneous patterns of staining with actin, tubulin, and calmodulin antibodies in contrast to normal and hyperplastic prostate, which showed uniform staining. The results suggest that a disturbance in the organization of the cytoskeleton may accompany neoplastic transformation of human prostate. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:2435158

  6. Elemental concentration analysis in prostate tissues using total reflection X-ray fluorescence

    NASA Astrophysics Data System (ADS)

    Leitão, R. G.; Palumbo, A.; Souza, P. A. V. R.; Pereira, G. R.; Canellas, C. G. L.; Anjos, M. J.; Nasciutti, L. E.; Lopes, R. T.

    2014-02-01

    Prostate cancer (PCa) currently represents the second most prevalent malignant neoplasia in men, representing 21% of all cancer cases. Benign Prostate Hyperplasia (BPH) is an illness prevailing in men above the age of 50, close to 90% after the age of 80. The prostate presents a high zinc concentration, about 10-fold higher than any other body tissue. In this work, samples of human prostate tissues with cancer, BPH and normal tissue were analyzed utilizing total reflection X-ray fluorescence spectroscopy using synchrotron radiation technique (SR-TXRF) to investigate the differences in the elemental concentrations in these tissues. SR-TXRF analyses were performed at the X-ray fluorescence beamline at Brazilian National Synchrotron Light Laboratory (LNLS), in Campinas, São Paulo. It was possible to determine the concentrations of the following elements: P, S, K, Ca, Fe, Cu, Zn and Rb. By using Mann-Whitney U test it was observed that almost all elements presented concentrations with significant differences (α=0.05) between the groups studied.

  7. Prostate cancer outcome and tissue levels of metal ions

    USGS Publications Warehouse

    Sarafanov, A.G.; Todorov, T.I.; Centeno, J.A.; MacIas, V.; Gao, W.; Liang, W.-M.; Beam, C.; Gray, Michael A.; Kajdacsy-Balla, A.

    2011-01-01

    BACKGROUND There are several studies examining prostate cancer and exposure to cadmium, iron, selenium, and zinc. Less data are available on the possible influence of these metal ions on prostate cancer outcome. This study measured levels of these ions in prostatectomy samples in order to examine possible associations between metal concentrations and disease outcome. METHODS We obtained formalin fixed paraffin embedded tissue blocks of prostatectomy samples of 40 patients with PSA recurrence, matched 1:1 (for year of surgery, race, age, Gleason grading, and pathology TNM classification) with tissue blocks from 40 patients without recurrence (n = 80). Case-control pairs were compared for the levels of metals in areas adjacent to tumors. Inductively coupled plasma-mass spectrometry (ICP-MS) was used for quantification of Cd, Fe, Zn, and Se. RESULTS Patients with biochemical (PSA) recurrence of disease had 12% lower median iron (95 ??g/g vs. 111 ??g/g; P = 0.04) and 21% lower zinc (279 ??g/g vs. 346 ??g/g; P = 0.04) concentrations in the normal-appearing tissue immediately adjacent to cancer areas. Differences in cadmium (0.489 ??g/g vs. 0.439 ??g/g; 4% higher) and selenium (1.68 ??g/g vs. 1.58 ??g/g; 5% higher) levels were not statistically significant in recurrence cases, when compared to non-recurrences (P = 0.40 and 0.21, respectively). CONCLUSIONS There is an association between low zinc and low iron prostate tissue levels and biochemical recurrence in prostate cancer. Whether these novel findings are a cause or effect of more aggressive tumors, or whether low zinc and iron prostatic levels raise implications for therapy, remains to be investigated. Copyright ?? 2011 Wiley-Liss, Inc.

  8. Candidate Serum Biomarkers for Prostate Adenocarcinoma Identified by mRNA Differences in Prostate Tissue and Verified with Protein Measurements in Tissue and Blood

    PubMed Central

    Klee, Eric W.; Bondar, Olga P.; Goodmanson, Marcia K.; Dyer, Roy B.; Erdogan, Sibel; Bergstralh, Eric J.; Bergen, H. Robert; Sebo, Thomas J.; Klee, George G.

    2014-01-01

    BACKGROUND Improved tests are needed for detection and management of prostate cancer. We hypothesized that differential gene expression in prostate tissue could help identify candidate blood biomarkers for prostate cancer and that blood from men with advanced prostate disease could be used to verify their presence in circulation. METHODS Candidate markers were identified using mRNA expression patterns from laser-capture microdissected prostate tissue. Tissue expression was confirmed using immunohistochemistry (IHC) for the subset of candidates having commercial antisera. Tissue extracts were analyzed with tandem mass spectrometry (MS/MS). Blood concentrations were measured using immunoassays and MS/MS of trypsin-digested, immuno-extracted peptides. RESULTS Thirty-five novel candidate prostate adenocarcinoma biomarkers were selected. Tissue expression was confirmed for all of the 13 markers having commercial antisera for IHC and six of these markers showed statistical discrimination between normal and malignant tissue. Only 5 of these markers were detected in tissue extracts using MS/MS. Sixteen of the 35 candidate markers were successfully assayed in blood. Four of eight biomarkers measured with ELISA and 3 of 10 biomarkers measured by targeted MS showed statistically significant increases in blood concentrations of advanced prostate cancer cases, compared to controls. CONCLUSION Seven novel biomarkers identified by gene expression profiles in prostate tissue were shown to have statistically significant increased levels in blood from men with advanced prostate adenocarcinoma compared to controls: APOC1, ASPN, COMP, CXCL11, CXCL9, F5, and PCSK6. PMID:22247499

  9. Raman Spectroscopy Study of Prostatic Adenocarcinoma Bulk Tissues

    NASA Astrophysics Data System (ADS)

    Devpura, S.; Dai, H.; Thakur, J. S.; Naik, R.; Cao, A.; Pandya, A.; Auner, G. W.; Sarkar, F.; Sakr, W.; Naik, V.

    2009-03-01

    Prostate cancer is one of the most common types of cancer among men. The mortality rate for this disease can be dramatically reduced if it can be diagnosed in its early stages. Raman spectroscopy is one of the optical techniques which can provide fingerprints of a disease in terms of its molecular composition which changes due to the onset of disease. The aim of this project is to investigate the differences in the Raman spectra to identify benign epithelium (BE), prostatic intraepithelial neoplasia (PIN) and adenocarcinoma of various Gleason grades in archived bulk tissues embedded in paraffin wax. For each tissue, two adjacent tissue sections were cut and dewaxed, where one of the sections was stained using haematoxylin and eosin for histological examination and the other unstained adjacent section was used for Raman spectroscopic studies. We have collected Raman spectra from 10 prostatic adenocarcinoma dewaxed tissue sections using Raman microscope (785 nm excitation laser). The data were analyzed using statistical methods of principal component analysis and discriminant function analysis to classify the tissue regions. The results indicate that Raman Spectroscopy can differentiate between BE, PIN and Cancer regions.

  10. Micro and bulk analysis of prostate tissues classified as hyperplasia

    NASA Astrophysics Data System (ADS)

    Kwiatek, W. M.; Banaś, A.; Banaś, K.; Cinque, G.; Dyduch, G.; Falkenberg, G.; Kisiel, A.; Marcelli, A.; Podgórczyk, M.

    2007-07-01

    BPH (Benign Prostatic Hyperplasia) is the most common benign neoplasm (non cancerous enlargement of the prostate gland), whose prevalence increases with age. The gland, when increased in size, exerts pressure on the urethra, causing obstruction to urine flow. The latter may result in severe urinary tract and kidney conditions. In this work prostate samples from patients diagnosed with BPH were analyzed using synchrotron radiation. Micro-analysis of the hyperplastic samples was carried out on the L-beam line at HASYLAB, DESY (Germany), while bulk analysis on selected samples was performed at the DRX2 beamline at LNF, Frascati (Italy). Microanalysis with a mono-energetic beam 15 μm in diameter confirmed that concentrations of certain elements, such as S, Mn, Cu, Fe and Zn, are good indicators of pathological disorders in prostate tissue that may be considered effective tracers of developing compliant. The concentrations of Mn, Cu, Fe and Zn are higher in hyperplastic tissues, as compared to normal ones, while for sulphur the opposite is observed. Additionally, Fe and S K-edge XANES (X-ray Absorption Near Edge Structure) spectroscopy experiments were carried out in order to determine the chemical speciation of these elements in our samples.

  11. Can Decellularised Prostate Tissue Be Used to Model Tumour Malignancy?

    PubMed

    Maitland, Norman J

    2016-10-01

    This editorial discusses how feasible it will be to predict the invasive capacity of human prostate cancers by measuring their invasion into decellularised extracellular matrix and stresses the multiple factors that affect local metastasis, including immune and stromal cells. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  12. Texture analysis of tissues in Gleason grading of prostate cancer

    NASA Astrophysics Data System (ADS)

    Alexandratou, Eleni; Yova, Dido; Gorpas, Dimitris; Maragos, Petros; Agrogiannis, George; Kavantzas, Nikolaos

    2008-02-01

    Prostate cancer is a common malignancy among maturing men and the second leading cause of cancer death in USA. Histopathological grading of prostate cancer is based on tissue structural abnormalities. Gleason grading system is the gold standard and is based on the organization features of prostatic glands. Although Gleason score has contributed on cancer prognosis and on treatment planning, its accuracy is about 58%, with this percentage to be lower in GG2, GG3 and GG5 grading. On the other hand it is strongly affected by "inter- and intra observer variations", making the whole process very subjective. Therefore, there is need for the development of grading tools based on imaging and computer vision techniques for a more accurate prostate cancer prognosis. The aim of this paper is the development of a novel method for objective grading of biopsy specimen in order to support histopathological prognosis of the tumor. This new method is based on texture analysis techniques, and particularly on Gray Level Co-occurrence Matrix (GLCM) that estimates image properties related to second order statistics. Histopathological images of prostate cancer, from Gleason grade2 to Gleason grade 5, were acquired and subjected to image texture analysis. Thirteen texture characteristics were calculated from this matrix as they were proposed by Haralick. Using stepwise variable selection, a subset of four characteristics were selected and used for the description and classification of each image field. The selected characteristics profile was used for grading the specimen with the multiparameter statistical method of multiple logistic discrimination analysis. The subset of these characteristics provided 87% correct grading of the specimens. The addition of any of the remaining characteristics did not improve significantly the diagnostic ability of the method. This study demonstrated that texture analysis techniques could provide valuable grading decision support to the pathologists

  13. A curated collection of tissue microarray images and clinical outcome data of prostate cancer patients.

    PubMed

    Zhong, Qing; Guo, Tiannan; Rechsteiner, Markus; Rüschoff, Jan H; Rupp, Niels; Fankhauser, Christian; Saba, Karim; Mortezavi, Ashkan; Poyet, Cédric; Hermanns, Thomas; Zhu, Yi; Moch, Holger; Aebersold, Ruedi; Wild, Peter J

    2017-03-14

    Microscopy image data of human cancers provide detailed phenotypes of spatially and morphologically intact tissues at single-cell resolution, thus complementing large-scale molecular analyses, e.g., next generation sequencing or proteomic profiling. Here we describe a high-resolution tissue microarray (TMA) image dataset from a cohort of 71 prostate tissue samples, which was hybridized with bright-field dual colour chromogenic and silver in situ hybridization probes for the tumour suppressor gene PTEN. These tissue samples were digitized and supplemented with expert annotations, clinical information, statistical models of PTEN genetic status, and computer source codes. For validation, we constructed an additional TMA dataset for 424 prostate tissues, hybridized with FISH probes for PTEN, and performed survival analysis on a subset of 339 radical prostatectomy specimens with overall, disease-specific and recurrence-free survival (maximum 167 months). For application, we further produced 6,036 image patches derived from two whole slides. Our curated collection of prostate cancer data sets provides reuse potential for both biomedical and computational studies.

  14. A curated collection of tissue microarray images and clinical outcome data of prostate cancer patients

    PubMed Central

    Zhong, Qing; Guo, Tiannan; Rechsteiner, Markus; Rüschoff, Jan H.; Rupp, Niels; Fankhauser, Christian; Saba, Karim; Mortezavi, Ashkan; Poyet, Cédric; Hermanns, Thomas; Zhu, Yi; Moch, Holger; Aebersold, Ruedi; Wild, Peter J.

    2017-01-01

    Microscopy image data of human cancers provide detailed phenotypes of spatially and morphologically intact tissues at single-cell resolution, thus complementing large-scale molecular analyses, e.g., next generation sequencing or proteomic profiling. Here we describe a high-resolution tissue microarray (TMA) image dataset from a cohort of 71 prostate tissue samples, which was hybridized with bright-field dual colour chromogenic and silver in situ hybridization probes for the tumour suppressor gene PTEN. These tissue samples were digitized and supplemented with expert annotations, clinical information, statistical models of PTEN genetic status, and computer source codes. For validation, we constructed an additional TMA dataset for 424 prostate tissues, hybridized with FISH probes for PTEN, and performed survival analysis on a subset of 339 radical prostatectomy specimens with overall, disease-specific and recurrence-free survival (maximum 167 months). For application, we further produced 6,036 image patches derived from two whole slides. Our curated collection of prostate cancer data sets provides reuse potential for both biomedical and computational studies. PMID:28291248

  15. Hydrodynamic cavitation kills prostate cells and ablates benign prostatic hyperplasia tissue.

    PubMed

    Itah, Zeynep; Oral, Ozlem; Perk, Osman Yavuz; Sesen, Muhsincan; Demir, Ebru; Erbil, Secil; Dogan-Ekici, A Isin; Ekici, Sinan; Kosar, Ali; Gozuacik, Devrim

    2013-11-01

    Hydrodynamic cavitation is a physical phenomenon characterized by vaporization and bubble formation in liquids under low local pressures, and their implosion following their release to a higher pressure environment. Collapse of the bubbles releases high energy and may cause damage to exposed surfaces. We recently designed a set-up to exploit the destructive nature of hydrodynamic cavitation for biomedical purposes. We have previously shown that hydrodynamic cavitation could kill leukemia cells and erode kidney stones. In this study, we analyzed the effects of cavitation on prostate cells and benign prostatic hyperplasia (BPH) tissue. We showed that hydrodynamic cavitation could kill prostate cells in a pressure- and time-dependent manner. Cavitation did not lead to programmed cell death, i.e. classical apoptosis or autophagy activation. Following the application of cavitation, we observed no prominent DNA damage and cells did not arrest in the cell cycle. Hence, we concluded that cavitation forces directly damaged the cells, leading to their pulverization. Upon application to BPH tissues from patients, cavitation could lead to a significant level of tissue destruction. Therefore similar to ultrasonic cavitation, we propose that hydrodynamic cavitation has the potential to be exploited and developed as an approach for the ablation of aberrant pathological tissues, including BPH.

  16. Do Black NonHispanic Men Produce Less Prostate Specific Antigen in Benign Prostate Tissue or Cancer Compared to White NonHispanic Men with Gleason Score 6 (Grade Group 1) Prostate Cancer?

    PubMed

    Kryvenko, Oleksandr N; Epstein, Jonathan I; Cote, Richard J

    2016-12-01

    We evaluated prostate specific antigen production by benign prostate tissue and Gleason score 3+3=6 (Grade Group 1) prostate cancer in black and white nonHispanic men. We used Gleason score 3+3=6 (Grade Group 1) cases to assess prostate specific antigen production by benign prostate tissue in cases with low volume cancer that did not influence prostate specific antigen and in those with high volume cancer in which gland weight did not influence prostate specific antigen. We then created age, prostate specific antigen and prostate weight adjusted cohorts to demonstrate tumor volume per 1 ng/ml prostate specific antigen and 1 μg prostate specific antigen mass. Prostate specific antigen density and prostate specific antigen mass density were used to adjust for prostate weight. Comparison of 58 black and 301 white men with low volume cancer demonstrated equal prostate specific antigen production by benign prostate tissue. Comparison of 30 black and 75 white men with high volume cancer indicated that prostate specific antigen was being driven by cancer volume, with lower prostate specific antigen production in black men. In the cohort of 54 black and 134 white men matched by age, prostate specific antigen and prostate weight, tumor volume per 1 ng/ml prostate specific antigen or 1 μg prostate specific antigen mass adjusted for prostate weight was 25% and 26% higher in black men, respectively. Benign prostate tissue produces equal amounts of prostate specific antigen in black and white men. Gleason score 3+3=6 (Grade Group 1) prostate cancer produces less prostate specific antigen in black men. These data should be considered for lowering prostate specific antigen and its derivatives in determining biopsy thresholds and for adjusting values for active surveillance criteria in black men. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  17. A comparison of virtual touch tissue quantification and digital rectal examination for discrimination between prostate cancer and benign prostatic hyperplasia.

    PubMed

    Zheng, Xiaozhi; Ji, Ping; Mao, Hongwei; Hu, Jianqun

    2012-03-01

    Virtual touch tissue quantification (VTTQ) is a new, promising technique for detecting the stiffness of tissues. The aim of this study is to compare the performance of VTTQ and digital rectal examination (DRE) in discrimination between prostate cancer and benign prostatic hyperplasia (BPH). VTTQ was performed in 209 prostate nodular lesions of 107 patients with BPH and suspected prostate cancer before the prostate histopathologic examination. The shear wave velocity (SWV) at each nodular lesion was quantified by implementing an acoustic radiation force impulse (ARFI). The performance of VTTQ and DRE in discrimination between prostate cancer and BPH was compared. The diagnostic value of VTTQ and DRE for prostate cancer was evaluated in terms of the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy. Prostate cancer was detected in 57 prostate nodular lesions by histopathologic examination. The SWV values (m/s) were significantly greater in prostate cancer and BPH than in normal prostate (2.37 ± 0.94, 1.98 ± 0.82 vs. 1.34 ± 0.47). The area under the receiver operating characteristic curve (AUC) for VTTQ (SWV>2.5m/s) to differentiate prostate nodules as benign hyperplasia or malignancy was 0.86, while it was 0.67 for DRE. The diagnostic sensitivity, specificity, PPV, NPV and accuracy were 71.93 %, 87.5 %, 68.33 %, 89.26 %, 83.25 %, respectively for VTTQ (SWV>2.5m/s), whereas they were 33.33 %, 81.57 %, 40.43 %, 76.54 %, 68.42 % respectively for DRE. VTTQ can effectively detect the stiffness of prostate nodular lesions, which has a significantly higher performance than DRE in discrimination between prostate cancer and BPH.

  18. Cell type specific gene expression analysis of prostate needle biopsies resolves tumor tissue heterogeneity

    PubMed Central

    Krönig, Malte; Walter, Max; Drendel, Vanessa; Werner, Martin; Jilg, Cordula A.; Richter, Andreas S.; Backofen, Rolf; McGarry, David; Follo, Marie; Schultze-Seemann, Wolfgang; Schüle, Roland

    2015-01-01

    A lack of cell surface markers for the specific identification, isolation and subsequent analysis of living prostate tumor cells hampers progress in the field. Specific characterization of tumor cells and their microenvironment in a multi-parameter molecular assay could significantly improve prognostic accuracy for the heterogeneous prostate tumor tissue. Novel functionalized gold-nano particles allow fluorescence-based detection of absolute mRNA expression levels in living cells by fluorescent activated flow cytometry (FACS). We use of this technique to separate prostate tumor and benign cells in human prostate needle biopsies based on the expression levels of the tumor marker alpha-methylacyl-CoA racemase (AMACR). We combined RNA and protein detection of living cells by FACS to gate for epithelial cell adhesion molecule (EPCAM) positive tumor and benign cells, EPCAM/CD45 double negative mesenchymal cells and CD45 positive infiltrating lymphocytes. EPCAM positive epithelial cells were further sub-gated into AMACR high and low expressing cells. Two hundred cells from each population and several biopsies from the same patient were analyzed using a multiplexed gene expression profile to generate a cell type resolved profile of the specimen. This technique provides the basis for the clinical evaluation of cell type resolved gene expression profiles as pre-therapeutic prognostic markers for prostate cancer. PMID:25514598

  19. [Human brown adipose tissue].

    PubMed

    Virtanen, Kirsi A; Nuutila, Pirjo

    2015-01-01

    Adult humans have heat-producing and energy-consuming brown adipose tissue in the clavicular region of the neck. There are two types of brown adipose cells, the so-called classic and beige adipose cells. Brown adipose cells produce heat by means of uncoupler protein 1 (UCP1) from fatty acids and sugar. By applying positron emission tomography (PET) measuring the utilization of sugar, the metabolism of brown fat has been shown to multiply in the cold, presumably influencing energy consumption. Active brown fat is most likely present in young adults, persons of normal weight and women, least likely in obese persons.

  20. Automated prostate tissue referencing for cancer detection and diagnosis.

    PubMed

    Kwak, Jin Tae; Hewitt, Stephen M; Kajdacsy-Balla, André Alexander; Sinha, Saurabh; Bhargava, Rohit

    2016-06-01

    The current practice of histopathology review is limited in speed and accuracy. The current diagnostic paradigm does not fully describe the complex and complicated patterns of cancer. To address these needs, we develop an automated and objective system that facilitates a comprehensive and easy information management and decision-making. We also develop a tissue similarity measure scheme to broaden our understanding of tissue characteristics. The system includes a database of previously evaluated prostate tissue images, clinical information and a tissue retrieval process. In the system, a tissue is characterized by its morphology. The retrieval process seeks to find the closest matching cases with the tissue of interest. Moreover, we define 9 morphologic criteria by which a pathologist arrives at a histomorphologic diagnosis. Based on the 9 criteria, true tissue similarity is determined and serves as the gold standard of tissue retrieval. Here, we found a minimum of 4 and 3 matching cases, out of 5, for ~80 % and ~60 % of the queries when a match was defined as the tissue similarity score ≥5 and ≥6, respectively. We were also able to examine the relationship between tissues beyond the Gleason grading system due to the tissue similarity scoring system. Providing the closest matching cases and their clinical information with pathologists will help to conduct consistent and reliable diagnoses. Thus, we expect the system to facilitate quality maintenance and quality improvement of cancer pathology.

  1. Detection of benign epithelia, prostatic intraepithelial neoplasia, and cancer regions in radical prostatectomy tissues using Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Devpura, Suneetha; Thakur, Jagdish S.; Naik, Ratna; Sarkar, Fazlul H.; Sakr, Wael A.; Naik, Vaman M.

    2010-04-01

    In this study we have investigated Benign Epithelia (BE), Prostatic Intraepithelial Neoplasia (PIN), adenocarcinoma, and different Gleason scores in human prostate bulk tissues using Raman spectroscopy. A careful investigation of the data shows that two main differences in the Raman spectral features of BE, PIN, and cancerous tissues: (i) a strong variations in the band intensities of certain bands, (ii) shift in certain band positions. In order to quantify these variations, Raman data were further analyzed using chemometric methods of Principal Component Analysis (PCA) and Discriminant Function Analysis (DFA). The PCA and DFA clearly separated the data into three main distinct pathological groups representing BE, PIN, and cancerous state in tissue. Similarly the analysis of the Raman data of tissues with different Gleason scores shows that the data can be categorized into three distinct groups representing Gleason scores 6, 7, and 8. The results of this study demonstrate that Raman spectroscopy can diagnose different stages of the prostate cancer.

  2. Sulphur XANES Analysis of Cultured Human Prostate Cancer Cells

    NASA Astrophysics Data System (ADS)

    Kwiatek, W. M.; Podgórczyk, M.; Paluszkiewicz, Cz.; Balerna, A.; Kisiel, A.

    2008-08-01

    Prostate cancer is one of the most commonly diagnosed cancers in men throughout the world. It is believed that changes to the structure of protein binding sites, altering its metabolism, may play an important role in carcinogenesis. Sulphur, often present in binding sites, can influence such changes through its chemical speciation. Hence there is a need for precise investigation of coordination environment of sulphur. X-ray absorption near edge structure spectroscopy offers such possibility. Cell culture samples offer histologically well defined areas of good homogeneity, suitable for successful and reliable X-ray absorption near edge structure analysis. This paper presents sulphur speciation data collected from three different human prostate cancer cell lines (PC-3, LNCaP and DU-145). Sulphur X-ray absorption near edge structure analysis was performed on K-edge structure. The spectra of cells were compared with those of cancerous tissue and with organic substances as well as inorganic compounds.

  3. Development of Assays for Detecting Significant Prostate Cancer Based on Molecular Alterations Associated with Cancer in Non-Neoplastic Prostate Tissue

    DTIC Science & Technology

    2012-10-01

    prostate cancer ." Am J Pathol 181(1): 34-42. Li, M. and L. A. Cannizzaro (1999). "Identical clonal origin of synchronous and metachronous low-grade...significant prostate cancer based on molecular alterations associated with cancer in non-neoplastic prostate tissue PRINCIPAL INVESTIGATOR...significant prostate cancer based on molecular alterations associated with cancer in non-neoplastic prostate tissue 5a. CONTRACT NUMBER 5b. GRANT

  4. Pilot Comparison of Stromal Gene Expression Among Normal Prostate Tissues and Primary Prostate Cancer Tissues in White and Black Men

    DTIC Science & Technology

    2007-09-01

    microdissection, and expression analysis of prostate-stroma specific cells in normal and cancerous prostates, and aims to develop preliminary data...differences in both normal epithelial and stromal cells from fully normal prostates as compared to prostates containing adenocarcinoma which are now...4 Introduction Recent advances in prostate biology suggest that stromal cells surrounding prostate epithelia may play a key role in

  5. Differentially Expressed Androgen-Regulated Genes in Androgen-Sensitive Tissues Reveal Potential Biomarkers of Early Prostate Cancer

    PubMed Central

    Altintas, Dogus Murat; Allioli, Nathalie; Decaussin, Myriam; de Bernard, Simon; Ruffion, Alain; Samarut, Jacques; Vlaeminck-Guillem, Virginie

    2013-01-01

    Background Several data favor androgen receptor implication in prostate cancer initiation through the induction of several gene activation programs. The aim of the study is to identify potential biomarkers for early diagnosis of prostate cancer (PCa) among androgen-regulated genes (ARG) and to evaluate comparative expression of these genes in normal prostate and normal prostate-related androgen-sensitive tissues that do not (or rarely) give rise to cancer. Methods ARG were selected in non-neoplastic adult human prostatic epithelial RWPE-1 cells stably expressing an exogenous human androgen receptor, using RNA-microarrays and validation by qRT-PCR. Expression of 48 preselected genes was quantified in tissue samples (seminal vesicles, prostate transitional zones and prostate cancers, benign prostatic hypertrophy obtained from surgical specimens) using TaqMan® low-density arrays. The diagnostic performances of these potential biomarkers were compared to that of genes known to be associated with PCa (i.e. PCA3 and DLX1). Results and Discussion By crossing expression studies in 26 matched PCa and normal prostate transitional zone samples, and 35 matched seminal vesicle and PCa samples, 14 genes were identified. Similarly, 9 genes were overexpressed in 15 benign prostatic hypertrophy samples, as compared to PCa samples. Overall, we selected 8 genes of interest to evaluate their diagnostic performances in comparison with that of PCA3 and DLX1. Among them, 3 genes: CRYAB, KCNMA1 and SDPR, were overexpressed in all 3 reference non-cancerous tissues. The areas under ROC curves of these genes reached those of PCA3 (0.91) and DLX1 (0.94). Conclusions We identified ARG with reduced expression in PCa and with significant diagnostic values for discriminating between cancerous and non-cancerous prostatic tissues, similar that of PCA3. Given their expression pattern, they could be considered as potentially protective against prostate cancer. Moreover, they could be complementary

  6. Metastasis initiating cells in primary prostate cancer tissues from transurethral resection of the prostate (TURP) predicts castration-resistant progression and survival of prostate cancer patients.

    PubMed

    Li, Qinlong; Li, Quanlin; Nuccio, Jill; Liu, Chunyan; Duan, Peng; Wang, Ruoxiang; Jones, Lawrence W; Chung, Leland W K; Zhau, Haiyen E

    2015-09-01

    We previously reported that the activation of RANK and c-Met signaling components in both experimental mouse models and human prostate cancer (PC) specimens predicts bone metastatic potential and PC patient survival. This study addresses whether a population of metastasis-initiating cells (MICs) known to express a stronger RANKL, phosphorylated c-Met (p-c-Met), and neuropilin-1 (NRP1) signaling network than bystander or dormant cells (BDCs) can be detected in PC tissues from patients subjected to transurethral resection of the prostate (TURP) for urinary obstruction prior to the diagnosis of PC with or without prior hormonal manipulation, and whether the relative abundance of MICs over BDCs could predict castration-resistant progression and PC patient survival. We employed a multiplexed quantum-dot labeling (mQDL) protocol to detect and quantify MICs and BDCs at the single cell level in TURP tissues obtained from 44 PC patients with documented overall survival and castration resistance status. PC tissues with a higher number of MICs and an activated RANK signaling network, including increased expression of RANKL, p-c-Met, and NRP1 compared to BDCs, were found to correlate with the development of castration resistance and overall survival. The assessment of PC cells with MIC and BDC phenotypes in primary PC tissues from hormone-naïve patients can predict the progression to castration resistance and the overall survival of PC patients. © 2015 Wiley Periodicals, Inc.

  7. Metastasis Initiating Cells in Primary Prostate Cancer Tissues From Transurethral Resection of the Prostate (TURP) Predicts Castration-Resistant Progression and Survival of Prostate Cancer Patients

    PubMed Central

    Li, Qinlong; Li, Quanlin; Nuccio, Jill; Liu, Chunyan; Duan, Peng; Wang, Ruoxiang; Jones, Lawrence W.; Chung, Leland W. K.; Zhau, Haiyen E.

    2016-01-01

    BACKGROUND We previouslyreported that the activation of RANK and c-Met signaling components in both experimental mouse models and human prostate cancer (PC) specimens predicts bone metastatic potential and PC patient survival. This study addresses whether a population of metastasis-initiating cells (MICs) known to express a stronger RANKL, phosphorylated c-Met (p-c-Met), and neuropilin-1 (NRP1) signaling network than bystander or dormant cells (BDCs) can be detected in PC tissues from patients subjected to transurethral resection of the prostate (TURP) for urinary obstruction prior to the diagnosis of PC with or without prior hormonal manipulation, and whether the relative abundance of MICs over BDCs could predict castration-resistant progression and PC patient survival. METHODS We employed a multiplexed quantum-dot labeling (mQDL) protocol to detect and quantify MICs and BDCs at the single cell level in TURP tissues obtained from 44 PC patients with documented overall survival and castration resistance status. RESULTS PC tissues with a higher number of MICs and an activated RANK signaling network, including increased expression of RANKL, p-c-Met, and NRP1 compared to BDCs, were found to correlate with the development of castration resistance and overall survival. CONCLUSIONS The assessment of PC cells with MIC and BDC phenotypes in primary PC tissues from hormone-naïve patients can predict the progression to castration resistance and the overall survival of PC patients. PMID:25990623

  8. Humanized Androgen Receptor Mice: A Genetic Model for Differential Response to Prostate Cancer Therapy

    DTIC Science & Technology

    2010-05-01

    For each Q tract allele, we have currently obtained at least 30 experimental and 30 control mice . Some have reached their time points and tissues...overexpression of ETV1). Experimental mice have been generated and prostates are being microdissected as animals reach their time points. Initial...TITLE: Humanized Androgen Receptor Mice : A Genetic Model for Differential Response to Prostate Cancer Therapy PRINCIPAL INVESTIGATOR: Diane M

  9. Enhanced distribution of fourth-generation fluoroquinolones in prostatic tissue.

    PubMed

    Perletti, G; Wagenlehner, F M E; Naber, K G; Magri, V

    2009-03-01

    A recently published pharmacokinetic trial showed that the fluoroquinolone moxifloxacin administered to healthy volunteers at the single oral dose of 400mg accumulates in prostatic secretions (PS) up to a median concentration of 3.99 mg/L and reaches a PS/plasma concentration ratio of 1.57, far higher than values shown by other fluoroquinolones such as norfloxacin (ratio 0.1) or ciprofloxacin (ratio 0.2). Ion trapping mechanisms were hypothesised to be among the determinants of this effect. However, whether ion trapping would solely account for the observed differences in fluoroquinolone pharmacokinetics was left to further research and discussion. In this hypothesis paper, we review various published evidence on the tissue distribution of moxifloxacin and other quinolones, suggesting that increased lipophilicity, binding to cellular matrices and fast cellular uptake/release kinetics may be mechanisms compatible with enhanced prostatic accumulation and secretion of fourth-generation fluoroquinolones.

  10. Sonohistology - ultrasonic tissue characterization for prostate cancer diagnostics.

    PubMed

    Scheipers, U; König, K; Sommerfeld, H-J; Garcia-Schürmann, M; Senge, T; Ermert, H

    2008-01-01

    A computer-aided diagnostic system for imaging prostate cancer has been developed in order to supplement today's conventional methods for the early detection of prostate carcinoma. The system is based on analysis of the spectral content of radiofrequency ultrasonic echo data in combination with evaluations of textural, contextual, morphological and clinical features in a multiparameter approach. A state-of-the-art, non-linear classifier, the so-called adaptive network-based fuzzy inference system, is used for higher-order classification of the underlying tissue-describing parameters. The system has been evaluated on radio-frequency ultrasound data originating from 100 patients using histological specimens obtained after prostatectomy as the gold standard. Leave-one-out cross-validation over patient data sets results in areas under the ROC curve of 0.86 +/- 0.01 for hypoechoic and hyperechoic tumors and of 0.84 +/- 0.02 for isoechoic tumors, respectively.

  11. Role of RUNX3 in suppressing metastasis and angiogenesis of human prostate cancer.

    PubMed

    Chen, Feifei; Wang, Meng; Bai, Jin; Liu, Qinghua; Xi, Yaguang; Li, Wang; Zheng, Junnian

    2014-01-01

    RUNX3 (runt-related transcription factor-3) has been reported to suppress tumor tumorigenesis and metastasis in different human cancers. In this study, we used tissue microarray (TMA) to determine the significance of RUNX3 in prostate cancer progession. Our results showed ectopic expression of RUNX3 in prostate cancer tissues when compared with tumor adjacent normal prostate tissues, and reduced RUNX3 staining was significantly correlated with TNM stage. Moreover, we demonstrated that RUNX3 overexpression inhibited prostate cancer cell migration and invasion resulting from the elevated upregulation of tissue inhibitor of matrix metalloproteinase-2 (TIMP-2), which subsequently inhibited metalloproteinase-2 (MMP-2) expression and activity in vitro. Knock down of RUNX3 expression broke up the balance of TIMP-2/MMP-2, whereas silence of TIMP-2 resulted in the inhibition of MMP-2 expression in prostate cells. We also showed that restoration of RUNX3 decreased vascular endothelial growth factor (VEGF) secretion and suppressed endothelial cell growth and tube formation. Strikingly, RUNX3 was demonstrated to inhibit tumor metastasis and angiogenesis in vivo. Altogether, our results support the tumor suppressive role of RUNX3 in human prostate cancer, and provide insights into development of targeted therapy for this disease.

  12. A Balanced Tissue Composition Reveals New Metabolic and Gene Expression Markers in Prostate Cancer

    PubMed Central

    Tessem, May-Britt; Bertilsson, Helena; Angelsen, Anders; Bathen, Tone F.; Drabløs, Finn; Rye, Morten Beck

    2016-01-01

    Molecular analysis of patient tissue samples is essential to characterize the in vivo variability in human cancers which are not accessible in cell-lines or animal models. This applies particularly to studies of tumor metabolism. The challenge is, however, the complex mixture of various tissue types within each sample, such as benign epithelium, stroma and cancer tissue, which can introduce systematic biases when cancers are compared to normal samples. In this study we apply a simple strategy to remove such biases using sample selections where the average content of stroma tissue is balanced between the sample groups. The strategy is applied to a prostate cancer patient cohort where data from MR spectroscopy and gene expression have been collected from and integrated on the exact same tissue samples. We reveal in vivo changes in cancer-relevant metabolic pathways which are otherwise hidden in the data due to tissue confounding. In particular, lowered levels of putrescine are connected to increased expression of SRM, reduced levels of citrate are attributed to upregulation of genes promoting fatty acid synthesis, and increased succinate levels coincide with reduced expression of SUCLA2 and SDHD. In addition, the strategy also highlights important metabolic differences between the stroma, epithelium and prostate cancer. These results show that important in vivo metabolic features of cancer can be revealed from patient data only if the heterogeneous tissue composition is properly accounted for in the analysis. PMID:27100877

  13. Early Growth Response1and Fatty Acid Synthase Expression is Altered in Tumor Adjacent Prostate Tissue and Indicates Field Cancerization

    PubMed Central

    Jones, Anna C.; Trujillo, Kristina A.; Phillips, Genevieve K.; Fleet, Trisha M.; Murton, Jaclyn K.; Severns, Virginia; Shah, Satyan K.; Davis, Michael S.; Smith, Anthony Y.; Griffith, Jeffrey K.; Fischer, Edgar G.; Bisoffi, Marco

    2011-01-01

    BACKGROUND Field cancerization denotes the occurrence of molecular alterations in histologically normal tissues adjacent to tumors. In prostate cancer, identification of field cancerization has several potential clinical applications. However, prostate field cancerization remains ill defined. Our previous work has shown up-regulated mRNA of the transcription factor early growth response 1 (EGR-1) and the lipogenic enzyme fatty acid synthase (FAS) in tissues adjacent to prostate cancer. METHODS Immunofluorescence data were analyzed quantitatively by spectral imaging and linear unmixing to determine the protein expression levels of EGR-1 and FAS in human cancerous, histologically normal adjacent, and disease-free prostate tissues. RESULTS EGR-1 expression was elevated in both structurally intact tumor adjacent (1.6× on average) and in tumor (3.0× on average) tissues compared to disease-free tissues. In addition, the ratio of cytoplasmic versus nuclear EGR-1 expression was elevated in both tumor adjacent and tumor tissues. Similarly, FAS expression was elevated in both tumor adjacent (2.7× on average) and in tumor (2.5× on average) compared to disease-free tissues. CONCLUSIONS EGR-1 and FAS expression is similarly deregulated in tumor and structurally intact adjacent prostate tissues and defines field cancerization. In cases with high suspicion of prostate cancer but negative biopsy, identification of field cancerization could help clinicians target areas for repeat biopsy. Field cancerization at surgical margins on prostatectomy specimen should also be looked at as a predictor of cancer recurrence. EGR-1 and FAS could also serve as molecular targets for chemoprevention. PMID:22127986

  14. Analysis of Mel-18 expression in prostate cancer tissues and correlation with clinicopathologic features.

    PubMed

    Wang, Wei; Lin, Tianxin; Huang, Jian; Hu, Weilie; Xu, Kewei; Liu, Jun

    2011-01-01

    Mel-18 is a member of the polycomb group (PcG) of proteins, which are chromatin regulatory factors that play an important role in development and oncogenesis. This study was designed to investigate the clinical and prognostic significance of Mel-18 in the patients with prostate cancer. Immunostaining with Mel-18 specific antibodies was performed on paraffin sections from 202 patients. Correlations between Mel-18 and the Gleason grading system, clinical stage, serum prostate-specific antigen (PSA) levels, and age were evaluated. PSA recurrence in 76 patients who underwent radical prostatectomy and survival in 59 patients with metastases at diagnosis were analyzed to evaluate the influence of Mel-18 expression in cancer progression using Kaplan-Meier analysis and multivariate Cox regression analysis. Staining was seen in all prostatic tissues. Mel-18 expression was significantly reduced in the prostate cancer patients with PSA levels over 100 ng/ml (P=0.009), advanced clinical stage (>T4, N1, or M1 disease, P=0.029), higher Gleason grade or with a higher Gleason score (P=0.018) than in those with other clinicopathologic features. Negative expression of Mel-18 was associated with significantly higher rates of PSA recurrence after radical prostatectomy than with positive expression of Mel-18 (P = 0.029), and was an independent predictor of PSA recurrence (P=0.034, HR=2.143) in multivariate analysis. Similarly, metastatic prostate cancer patients with negative expression of Mel-18 showed significantly worse survival compared with the positive expression of Mel-18 (P=0.025). In multivariate analysis, negative expression of Mel-18 was an independent predictor of cancer-specific survival (P=0.024, HR=2.365). Our study provides important evidence for the recognition of Mel-18 as a tumor suppressor. The expression of Mel-18 showed potential as a prognostic marker for human prostate cancer. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Frequency analysis of multispectral photoacoustic images for differentiating malignant region from normal region in excised human prostate

    NASA Astrophysics Data System (ADS)

    Sinha, Saugata; Rao, Navalgund A.; Valluru, Keerthi S.; Chinni, Bhargava K.; Dogra, Vikram S.; Helguera, Maria

    2014-03-01

    Frequency domain analysis of the photoacoustic (PA) radio frequency signals can potentially be used as a tool for characterizing microstructure of absorbers in tissue. This study investigates the feasibility of analyzing the spectrum of multiwavelength PA signals generated by excised human prostate tissue samples to differentiate between malignant and normal prostate regions. Photoacoustic imaging at five different wavelengths, corresponding to peak absorption coefficients of deoxyhemoglobin, whole blood, oxyhemoglobin, water and lipid in the near infrared (NIR) (700 nm - 1000 nm) region, was performed on freshly excised prostate specimens taken from patients undergoing prostatectomy for biopsy confirmed prostate cancer. The PA images were co-registered with the histopathology images of the prostate specimens to determine the region of interest (ROI) corresponding to malignant and normal tissue. The calibrated power spectrum of each PA signal from a selected ROI was fit to a linear model to extract the corresponding slope, midband fit and intercept parameters. The mean value of each parameter corresponding to malignant and adjacent normal prostate ROI was calculated for each of the five wavelengths. The results obtained for 9 different human prostate specimens, show that the mean values of midband fit and intercept are significantly different between malignant and normal regions. In addition, the average midband fit and intercept values show a decreasing trend with increasing wavelength. These preliminary results suggest that frequency analysis of multispectral PA signals can be used to differentiate malignant region from the adjacent normal region in human prostate tissue.

  16. Analysis of genetically engineered oncolytic herpes simplex viruses in human prostate cancer organotypic cultures.

    PubMed

    Passer, B J; Wu, C-l; Wu, S; Rabkin, S D; Martuza, R L

    2009-12-01

    Oncolytic herpes simplex viruses type 1 (oHSVs) such as G47Delta and G207 are genetically engineered for selective replication competence in cancer cells. Several factors can influence the overall effectiveness of oHSV tropism, including HSV-1 receptor expression, extracellular matrix milieu and cellular permissiveness. We have taken advantage of human prostate organ cultures derived from radical prostatectomies to investigate oHSV tropism. In this study, we show that both G47Delta and G207 specifically replicate in epithelial cells of the prostatic glands but not in the surrounding stroma. In contrast, both the epithelial and stromal cell compartments were readily infected by wild-type HSV-1. Analysis of oHSV replication in prostate surgical specimens 3 days post infection showed that G47Delta generated approximately 30-fold more viral progeny than did G207. This correlated with the enhanced expression of G47Delta-derived glycoprotein gB protein levels as compared with G207. In benign prostate tissues, G207 and G47Delta titers were notably reduced, whereas strain F titers were maintained at similar levels compared with prostate cancer specimens. Overall, our results show that these oncolytic herpes vectors show both target specificity and replication competence in human prostate cancer specimens and point to the utility of using human prostate organ cultures in assessing oHSV tropism and cellular specificity.

  17. Human Tissue Stimulator

    NASA Technical Reports Server (NTRS)

    1982-01-01

    Neurodyne Corporation Human Tissue Stimulator (HTS) is a totally implantable system used for treatment of chronic pain and involuntary motion disorders by electrical stimulation. It was developed by Pacesetter Systems, Inc. in cooperation with the Applied Physics Laboratory. HTS incorporates a nickel cadmium battery, telemetry and command systems technologies of the same type as those used in NASA's Small Astronomy Satellite-3 in microminiature proportions so that the implantable element is the size of a deck of cards. The stimulator includes a rechargeable battery, an antenna and electronics to receive and process commands and to report on its own condition via telemetry, a wireless process wherein instrument data is converted to electrical signals and sent to a receiver where signals are presented as usable information. The HTS is targeted to nerve centers or to particular areas of the brain to provide relief from intractable pain or arrest involuntary motion. The nickel cadmium battery can be recharged through the skin. The first two HTS units were implanted last year and have been successful. Extensive testing is required before HTS can be made available for general use.

  18. Is Human Papillomavirus Associated with Prostate Cancer Survival?

    PubMed Central

    Barbazza, Renzo; Marongiu, Barbara; Bonin, Serena; Stanta, Giorgio

    2013-01-01

    The role of human papillomavirus (HPV) in prostate carcinogenesis is highly controversial: some studies suggest a positive association between HPV infection and an increased risk of prostate cancer (PCa), whereas others do not reveal any correlation. In this study, we investigated the prognostic impact of HPV infection on survival in 150 primary PCa patients. One hundred twelve (74.67%) patients had positive expression of HPV E7 protein, which was evaluated in tumour tissue by immunohistochemistry. DNA analysis on a subset of cases confirmed HPV infection and revealed the presence of genotype 16. In Kaplan-Meier analysis, HPV-positive cancer patients showed worse overall survival (OS) (median 4.59 years) compared to HPV-negative (median 8.24 years, P = 0.0381). In multivariate analysis age (P < 0.001), Gleason score (P < 0.001), nuclear grading (P = 0.002), and HPV status (P = 0.034) were independent prognostic factors for OS. In our cohort, we observed high prevalence of HPV nuclear E7 oncoprotein and an association between HPV infection and PCa survival. In the debate about the oncogenic activity of HPV in PCa, our results further confirm the need for additional studies to clarify the possible role of HPV in prostate carcinogenesis. PMID:24288430

  19. Optical characteristics of prostate tissues and the key chromophores and fluorophores within tissues related to carcinogenesis

    NASA Astrophysics Data System (ADS)

    Zhou, Kenneth J.; Chen, Jun

    2015-03-01

    Tissues are an impressive complex creation comprised of a vast of assortment of molecules, structures and functional units. Despite this overwhelming complexity, we may still discuss average optical properties as long as we realize the limitations involved. There are five independent macroscopic parameters that are believed to characterize light propagation in tissue: the index of refraction (n), the absorption coefficient (μa), the scattering coefficient (μs), the reduced scattering coefficient (μ's), and the scattering anisotropy (g). This paper summarizes the Optical characteristics of tissue of prostate tissues ex vivo and the key fluorophores related to carcinogenesis. The absorption coefficient (μa) describes the effectiveness of light absorbed by certain chromophore. The key spectra fingerprints of water were introduced to distinguish different water contents in normal and cancerous prostate tissues. Fluorescence occurs when a molecule, atom or nanostructure relaxes to its ground state after being electrically excited. There are three fluorescence parameters of interest we may concern in tissue optics: the fluorescence lifetime (τf), the fluorescence quantum yield (Φ) and the fluorescence emission peak (λmax). The key wavelengths which can be used for cancer detection were reviewed. Scattering of light occurs in media which contains fluctuations in the refractive index n. Tissue ultrastructure extends from membranes to membrane aggregates to collagen fibers to nuclei to cells, which may be an alternative way to detect cancer in tissues.

  20. Poly (ADP-ribose) Polymerase 1 Protein Expression in Normal and Neoplastic Prostatic Tissue

    PubMed Central

    Salemi, M.; Galia, A.; Fraggetta, F.; La Corte, C.; Pepe, P.; La Vignera, S.; Improta, G.; Bosco, P.; Calogero, A.E.

    2013-01-01

    A genetic background has been implicated in the development of prostate cancer. Protein microarrays have enabled the identification of proteins, some of which associated with apoptosis, that may play a role in the development of such a tumor. Inhibition of apoptosis is a co-factor that contributes to the onset and progression of prostate cancer, though the molecular mechanisms are not entirely understood. Poly (ADP-ribose) polymerase 1 (PARP-1) gene is required for translocation of the apoptosis-inducing factor (AIF) from the mitochondria to the nucleus. Hence, it is involved in programmed cell death. Different PARP-1 gene expression has been observed in various tumors such as glioblastoma, lung, ovarian, endometrial, and skin cancers. We evaluated the expression of PARP-1 protein in prostatic cancer and normal prostate tissues by immunohistochemistry in 40 men with prostate cancer and in 37 normal men. Positive nuclear PARP-1 staining was found in all samples (normal prostate and prostate cancer tissues). No cytoplasmic staining was observed in any sample. PARP-1-positive cells resulted significantly higher in patients with prostate carcinoma compared with controls (P<0.001). PARP-1 over-expression in prostate cancer tissue compared with normal prostate suggests a greater activity of PARP-1 in these tumors. These findings suggest that PARP-1 expression in prostate cancer is an attempt to trigger apoptosis in this type of tumor similarly to what reported in other cancers. PMID:23807292

  1. Androgen responsive adult human prostatic epithelial cell lines immortalized by human papillomavirus 18.

    PubMed

    Bello, D; Webber, M M; Kleinman, H K; Wartinger, D D; Rhim, J S

    1997-06-01

    Prostate cancer and benign tumors of the prostate are the two most common neoplastic diseases in men in the United States, however, research on their causes and treatment has been slow because of the difficulty in obtaining fresh samples of human tissue and a lack of well characterized cell lines which exhibit growth and differentiation characteristics of normal prostatic epithelium. Non-neoplastic adult human prostatic epithelial cells from a white male donor were immortalized with human papillomavirus 18 which resulted in the establishment of the RWPE-1 cell line. Cells from the RWPE-1 cell line were further transformed by v-Ki-ras to establish the RWPE-2 cell line. The objectives of this study were to: (1) establish the prostatic epithelial origin and androgen responsiveness of RWPE-1 and RWPE-2 cell lines; (2) examine their response to growth factors; and (3) establish the malignant characteristics of the RWPE-2 cell line. Immunoperoxidase staining showed that both RWPE-1 and RWPE-2 cells express cytokeratins 8 and 18, which are characteristic of luminal prostatic epithelial cells, but they also coexpress basal cell cytokeratins. These cell lines show growth stimulation and prostate specific antigen (PSA) and androgen receptor (AR) expression in response to the synthetic androgen mibolerone, which establishes their prostatic epithelial origin. Both cell lines also show a dose-dependent growth stimulation by EGF and bFGF and growth inhibition when exposed to TGF-beta, however, the transformed RWPE-2 cells are less responsive. RWPE-1 cells neither grow in agar nor form tumors when injected into nude mice with or without Matrigel. However, RWPE-2 cells form colonies in agar and tumors in nude mice. In the in vitro invasion assay, RWPE-1 cells are not invasive whereas RWPE-2 cells are invasive. Nuclear expression of p53 and Rb proteins was heterogeneous but detectable by immunostaining in both cell lines. The RWPE-1 cells, which show many normal cell

  2. Feature-based analysis of mouse prostatic intraepithelial neoplasia in histological tissue sections

    PubMed Central

    Ruusuvuori, Pekka; Valkonen, Mira; Nykter, Matti; Visakorpi, Tapio; Latonen, Leena

    2016-01-01

    This paper describes work presented at the Nordic Symposium on Digital Pathology 2015, in Linköping, Sweden. Prostatic intraepithelial neoplasia (PIN) represents premalignant tissue involving epithelial growth confined in the lumen of prostatic acini. In the attempts to understand oncogenesis in the human prostate, early neoplastic changes can be modeled in the mouse with genetic manipulation of certain tumor suppressor genes or oncogenes. As with many early pathological changes, the PIN lesions in the mouse prostate are macroscopically small, but microscopically spanning areas often larger than single high magnification focus fields in microscopy. This poses a challenge to utilize full potential of the data acquired in histological specimens. We use whole prostates fixed in molecular fixative PAXgene™, embedded in paraffin, sectioned through and stained with H&E. To visualize and analyze the microscopic information spanning whole mouse PIN (mPIN) lesions, we utilize automated whole slide scanning and stacked sections through the tissue. The region of interests is masked, and the masked areas are processed using a cascade of automated image analysis steps. The images are normalized in color space, after which exclusion of secretion areas and feature extraction is performed. Machine learning is utilized to build a model of early PIN lesions for determining the probability for histological changes based on the calculated features. We performed a feature-based analysis to mPIN lesions. First, a quantitative representation of over 100 features was built, including several features representing pathological changes in PIN, especially describing the spatial growth pattern of lesions in the prostate tissue. Furthermore, we built a classification model, which is able to align PIN lesions corresponding to grading by visual inspection to more advanced and mild lesions. The classifier allowed both determining the probability of early histological changes for uncategorized

  3. Honokiol, a constituent of Magnolia species, inhibits adrenergic contraction of human prostate strips and induces stromal cell death.

    PubMed

    Herrmann, Daniel; Schreiber, Andrea; Ciotkowska, Anna; Strittmatter, Frank; Waidelich, Raphaela; Stief, Christian G; Gratzke, Christian; Hennenberg, Martin

    2014-09-01

    Smooth muscle contraction and prostate growth are important targets for medical therapy of lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia. Honokiol and Magnolol are lignan constituents of Magnolia species, which are used in traditional Asian medicine. Here, we examined effects of honokiol and magnolol on contraction of human prostate tissue and on growth of stromal cells. Prostate tissues were obtained from radical prostatectomy. Contraction of prostate strips was examined in organ bath studies. Effects in stromal cells were assessed in cultured immortalized human prostate stromal cells (WPMY-1). Ki-67 mRNA was assessed by reverse transcription-polymerase chain reaction, and proliferation by a fluorescence 5-ethynyl-2'-deoxyuridine assay. Honokiol (100μM) reduced noradrenaline-induced contractions, which was significant at 10 to 100μM noradrenaline. Honokiol reduced phenylephrine-induced contractions, which was significant at 3 to 100μM phenylephrine. Honokiol reduced electric field stimulation-induced contractions very slightly. In WPMY-1 cells, honokiol (24 hours) induced cell death. Magnolol (100μM) was without effects on contraction, and cellular viability. Honokiol inhibits smooth muscle contraction in the human prostate, and induces cell death in cultured stromal cells. Because prostate smooth muscle tone and prostate growth may cause LUTS, it appears possible that honokiol improves voiding symptoms.

  4. Establishment and Genomic Characterization of Mouse Xenografts of Human Primary Prostate Tumors

    PubMed Central

    Priolo, Carmen; Agostini, Michelle; Vena, Natalie; Ligon, Azra H.; Fiorentino, Michelangelo; Shin, Eyoung; Farsetti, Antonella; Pontecorvi, Alfredo; Sicinska, Ewa; Loda, Massimo

    2010-01-01

    Serum prostate-specific antigen screening has led to earlier detection and surgical treatment of prostate cancer, favoring an increasing incidence-to-mortality ratio. However, about one third of tumors that are diagnosed when still confined to the prostate can relapse within 10 years from the first treatment. The challenge is therefore to identify prognostic markers of aggressive versus indolent tumors. Although several preclinical models of advanced prostate tumors are available, a model that recapitulates the genetic and growth behavior of primary tumors is still lacking. Here, we report a complete histopathological and genomic characterization of xenografts derived from primary localized low- and high-grade human prostate tumors that were implanted under the renal capsule of immunodeficient mice. We obtained a tumor take of 56% and show that these xenografts maintained the histological as well as most genomic features of the parental tumors. Serum prostate-specific antigen levels were measurable only in tumor xenograft-bearing mice, but not in those implanted with either normal prostate tissue or in tumors that likely regressed. Finally, we show that a high proliferation rate, but not the pathological stage or the Gleason grade of the original tumor, was a fundamental prerequisite for tumor take in mice. This mouse xenograft model represents a useful preclinical model of primary prostate tumors for their biological characterization, biomarker discovery, and drug testing. PMID:20167861

  5. Expression analysis onto microarrays of randomly selected cDNA clones highlights HOXB13 as a marker of human prostate cancer

    PubMed Central

    Edwards, S; Campbell, C; Flohr, P; Shipley, J; Giddings, I; te-Poele, R; Dodson, A; Foster, C; Clark, J; Jhavar, S; Kovacs, G; Cooper, C S

    2004-01-01

    In a strategy aimed at identifying novel markers of human prostate cancer, we performed expression analysis using microarrays of clones randomly selected from a cDNA library prepared from the LNCaP prostate cancer cell line. Comparisons of expression profiles in primary human prostate cancer, adjacent normal prostate tissue, and a selection of other (nonprostate) normal human tissues, led to the identification of a set of clones that were judged as the best candidate markers of normal and/or malignant prostate tissue. DNA sequencing of the selected clones revealed that they included 10 genes that had previously been established as prostate markers: NKX3.1, KLK2, KLK3 (PSA), FOLH1 (PSMA), STEAP2, PSGR, PRAC, RDH11, Prostein and FASN. Following analysis of the expression patterns of all selected and sequenced genes through interrogation of SAGE databases, a further three genes from our clone set, HOXB13, SPON2 and NCAM2, emerged as additional candidate markers of human prostate cancer. Quantitative RT–PCR demonstrated the specificity of expression of HOXB13 in prostate tissue and revealed its ubiquitous expression in a series of 37 primary prostate cancers and 20 normal prostates. These results demonstrate the utility of this expression-microarray approach in hunting for new markers of individual human cancer types. PMID:15583692

  6. Expression analysis onto microarrays of randomly selected cDNA clones highlights HOXB13 as a marker of human prostate cancer.

    PubMed

    Edwards, S; Campbell, C; Flohr, P; Shipley, J; Giddings, I; Te-Poele, R; Dodson, A; Foster, C; Clark, J; Jhavar, S; Kovacs, G; Cooper, C S

    2005-01-31

    In a strategy aimed at identifying novel markers of human prostate cancer, we performed expression analysis using microarrays of clones randomly selected from a cDNA library prepared from the LNCaP prostate cancer cell line. Comparisons of expression profiles in primary human prostate cancer, adjacent normal prostate tissue, and a selection of other (nonprostate) normal human tissues, led to the identification of a set of clones that were judged as the best candidate markers of normal and/or malignant prostate tissue. DNA sequencing of the selected clones revealed that they included 10 genes that had previously been established as prostate markers: NKX3.1, KLK2, KLK3 (PSA), FOLH1 (PSMA), STEAP2, PSGR, PRAC, RDH11, Prostein and FASN. Following analysis of the expression patterns of all selected and sequenced genes through interrogation of SAGE databases, a further three genes from our clone set, HOXB13, SPON2 and NCAM2, emerged as additional candidate markers of human prostate cancer. Quantitative RT-PCR demonstrated the specificity of expression of HOXB13 in prostate tissue and revealed its ubiquitous expression in a series of 37 primary prostate cancers and 20 normal prostates. These results demonstrate the utility of this expression-microarray approach in hunting for new markers of individual human cancer types.

  7. Gene expression profiling of prostate tissue identifies chromatin regulation as a potential link between obesity and lethal prostate cancer.

    PubMed

    Ebot, Ericka M; Gerke, Travis; Labbé, David P; Sinnott, Jennifer A; Zadra, Giorgia; Rider, Jennifer R; Tyekucheva, Svitlana; Wilson, Kathryn M; Kelly, Rachel S; Shui, Irene M; Loda, Massimo; Kantoff, Philip W; Finn, Stephen; Vander Heiden, Matthew G; Brown, Myles; Giovannucci, Edward L; Mucci, Lorelei A

    2017-07-12

    Obese men are at higher risk of advanced prostate cancer and cancer-specific mortality; however, the biology underlying this association remains unclear. This study examined gene expression profiles of prostate tissue to identify biological processes differentially expressed by obesity status and lethal prostate cancer. Gene expression profiling was performed on tumor (n = 402) and adjacent normal (n = 200) prostate tissue from participants in 2 prospective cohorts who had been diagnosed with prostate cancer from 1982 to 2005. Body mass index (BMI) was calculated from the questionnaire immediately preceding cancer diagnosis. Men were followed for metastases or prostate cancer-specific death (lethal disease) through 2011. Gene Ontology biological processes differentially expressed by BMI were identified using gene set enrichment analysis. Pathway scores were computed by averaging the signal intensities of member genes. Odds ratios (ORs) for lethal prostate cancer were estimated with logistic regression. Among 402 men, 48% were healthy weight, 31% were overweight, and 21% were very overweight/obese. Fifteen gene sets were enriched in tumor tissue, but not normal tissue, of very overweight/obese men versus healthy-weight men; 5 of these were related to chromatin modification and remodeling (false-discovery rate < 0.25). Patients with high tumor expression of chromatin-related genes had worse clinical characteristics (Gleason grade > 7, 41% vs 17%; P = 2 × 10(-4) ) and an increased risk of lethal disease that was independent of grade and stage (OR, 5.26; 95% confidence interval, 2.37-12.25). This study improves our understanding of the biology of aggressive prostate cancer and identifies a potential mechanistic link between obesity and prostate cancer death that warrants further study. Cancer 2017. © 2017 American Cancer Society. © 2017 American Cancer Society.

  8. Melatonin as a negative mitogenic hormonal regulator of human prostate epithelial cell growth: potential mechanisms and clinical significance.

    PubMed

    Tam, Chun W; Chan, Kwok W; Liu, Vincent W S; Pang, Bo; Yao, Kwok-Ming; Shiu, Stephen Y W

    2008-11-01

    Circannual variation in the human serum levels of prostate-specific antigen, a growth marker of the prostate gland, has been reported recently. The present study was conducted to investigate the role of the photoperiodic hormone melatonin (MLT) and its membrane receptors in the modulation of human prostate growth. Expression of MT(1) and MT(2) receptors was detected in benign human prostatic epithelial tissues and RWPE-1 cells. MLT and 2-iodomelatonin inhibited RWPE-1 cell proliferation and up-regulated p27(Kip1) gene and protein expression in the cells. The effects of MLT were blocked by the nonselective MT(1)/MT(2) receptor antagonist luzindole, but were not affected by the selective MT(2) receptor antagonist 4-phenyl-2-propionamidotetraline. Of note, the antiproliferative action of MLT on benign prostate epithelial RWPE-1 cells was effected via increased p27(Kip1) gene transcription through MT(1) receptor-mediated activation of protein kinase A (PKA) and protein kinase C (PKC) in parallel, a signaling process which has previously been demonstrated in 22Rv1 prostate cancer cells. Taken together, the demonstration of the MT(1)/PKA+PKC/p27(Kip1) antiproliferative pathway in benign and malignant prostate epithelial cell lines indicated the potential importance of this MLT receptor-mediated signaling mechanism in growth regulation of the human prostate gland in health and disease. Collectively, our data support the hypothesis that MLT may function as a negative mitogenic hormonal regulator of human prostate epithelial cell growth.

  9. Zinc transporter mRNA expression in the RWPE-1 human prostate epithelial cell line.

    PubMed

    Albrecht, Amy L; Somji, Seema; Sens, Mary Ann; Sens, Donald A; Garrett, Scott H

    2008-08-01

    The human prostate gland undergoes a prominent alteration in Zn+2 homeostasis during the development of prostate cancer. The goal of the present study was to determine if the immortalized human prostate cell line (RWPE-1) could serve as a model system to study the role of zinc in prostate cancer. The study examined the expression of mRNA for 19 members of the zinc transporter gene family in normal prostate tissue, the prostate RWPE-1 cell line, and the LNCaP, DU-145 and PC-3 prostate cancer cell lines. The study demonstrated that the expression of the 19 zinc transporters was similar between the RWPE-1 cell line and the in situ prostate gland. Of the 19 zinc transporters, only 5 had levels that were different between the RWPE-1 cells and the tissue samples; all five being increased (ZnT-6, Zip-1, Zip-3A, Zip-10, and Zip-14). The response of the 19 transporters was also determined when the cell lines were exposed to 75 microM Zn+2 for 24 h. It was shown for the RWPE-1 cells that only 5 transporters responded to Zn+2 with mRNA for ZnT-1 and ZnT-2 being increased while mRNA for ZnT-7, Zip-7 and Zip-10 transporters were decreased. It was shown for the LNCaP, DU-145 and PC-3 cells that Zn+2 had no effect on the mRNA levels of all 19 transporters except for an induction of ZnT-1 in PC-3 cells. Overall, the study suggests that the RWPE-1 cells could be a valuable model for the study of the zinc transporter gene family in the prostate.

  10. An informatics model for tissue banks – Lessons learned from the Cooperative Prostate Cancer Tissue Resource

    PubMed Central

    Patel, Ashokkumar A; Gilbertson, John R; Parwani, Anil V; Dhir, Rajiv; Datta, Milton W; Gupta, Rajnish; Berman, Jules J; Melamed, Jonathan; Kajdacsy-Balla, Andre; Orenstein, Jan; Becich, Michael J

    2006-01-01

    Background Advances in molecular biology and growing requirements from biomarker validation studies have generated a need for tissue banks to provide quality-controlled tissue samples with standardized clinical annotation. The NCI Cooperative Prostate Cancer Tissue Resource (CPCTR) is a distributed tissue bank that comprises four academic centers and provides thousands of clinically annotated prostate cancer specimens to researchers. Here we describe the CPCTR information management system architecture, common data element (CDE) development, query interfaces, data curation, and quality control. Methods Data managers review the medical records to collect and continuously update information for the 145 clinical, pathological and inventorial CDEs that the Resource maintains for each case. An Access-based data entry tool provides de-identification and a standard communication mechanism between each group and a central CPCTR database. Standardized automated quality control audits have been implemented. Centrally, an Oracle database has web interfaces allowing multiple user-types, including the general public, to mine de-identified information from all of the sites with three levels of specificity and granularity as well as to request tissues through a formal letter of intent. Results Since July 2003, CPCTR has offered over 6,000 cases (38,000 blocks) of highly characterized prostate cancer biospecimens, including several tissue microarrays (TMA). The Resource developed a website with interfaces for the general public as well as researchers and internal members. These user groups have utilized the web-tools for public query of summary data on the cases that were available, to prepare requests, and to receive tissues. As of December 2005, the Resource received over 130 tissue requests, of which 45 have been reviewed, approved and filled. Additionally, the Resource implemented the TMA Data Exchange Specification in its TMA program and created a computer program for

  11. An informatics model for tissue banks--lessons learned from the Cooperative Prostate Cancer Tissue Resource.

    PubMed

    Patel, Ashokkumar A; Gilbertson, John R; Parwani, Anil V; Dhir, Rajiv; Datta, Milton W; Gupta, Rajnish; Berman, Jules J; Melamed, Jonathan; Kajdacsy-Balla, Andre; Orenstein, Jan; Becich, Michael J

    2006-05-05

    Advances in molecular biology and growing requirements from biomarker validation studies have generated a need for tissue banks to provide quality-controlled tissue samples with standardized clinical annotation. The NCI Cooperative Prostate Cancer Tissue Resource (CPCTR) is a distributed tissue bank that comprises four academic centers and provides thousands of clinically annotated prostate cancer specimens to researchers. Here we describe the CPCTR information management system architecture, common data element (CDE) development, query interfaces, data curation, and quality control. Data managers review the medical records to collect and continuously update information for the 145 clinical, pathological and inventorial CDEs that the Resource maintains for each case. An Access-based data entry tool provides de-identification and a standard communication mechanism between each group and a central CPCTR database. Standardized automated quality control audits have been implemented. Centrally, an Oracle database has web interfaces allowing multiple user-types, including the general public, to mine de-identified information from all of the sites with three levels of specificity and granularity as well as to request tissues through a formal letter of intent. Since July 2003, CPCTR has offered over 6,000 cases (38,000 blocks) of highly characterized prostate cancer biospecimens, including several tissue microarrays (TMA). The Resource developed a website with interfaces for the general public as well as researchers and internal members. These user groups have utilized the web-tools for public query of summary data on the cases that were available, to prepare requests, and to receive tissues. As of December 2005, the Resource received over 130 tissue requests, of which 45 have been reviewed, approved and filled. Additionally, the Resource implemented the TMA Data Exchange Specification in its TMA program and created a computer program for calculating PSA recurrence

  12. Selection and characterization of DNA aptamer for metastatic prostate cancer recognition and tissue imaging

    PubMed Central

    Wu, Xiaoqiu; Sun, Yang; Li, Jianglin; Hu, Xiaoxiao; Lin, Wei; Han, Dongmei; Zhao, Yifan; Liu, Jing; Ye, Mao; Tan, Weihong

    2016-01-01

    Prostate cancer (PCa) is the second leading cause of death and most prevalent cancer in men. The absence of curative options for castration-resistant metastatic prostate cancer and biomarkers able to discriminate between indolent and aggressive tumors contribute to these statistics. In this study, a DNA aptamer termed DML-7 was successfully selected against human PCa cell line DU145 by using the cell-based systematic evolution of ligands by exponential enrichment (SELEX) method. The selected aptamer DML-7 was found to internalize into target cells in a temperature-dependent manner and exhibit high binding affinity for target cells with dissociation constants in the nanomolar range. Binding analysis further revealed that DML-7 only binds to DU145 and PC-3 cells with metastatic potential, but not to LNCaP or 22Rv1 cells with low or nonmetastatic potential, demonstrating that DML-7 has excellent selectivity for the recognition of the metastatic PCa cells. Clinical tissue imaging further confirmed these results. Therefore, both high binding affinity and specificity to metastatic PCa cells and tissues afford DML-7 with the potential for development into a novel tool for diagnosis and targeted drug delivery against metastatic prostate cancer. PMID:27183906

  13. Dual tumor suppressing and promoting function of Notch1 signaling in human prostate cancer

    PubMed Central

    Lefort, Karine; Ostano, Gian Paola; Mello-Grand, Maurizia; Calpini, Valérie; Scatolini, Maria; Farsetti, Antonella; Dotto, Gian Paolo; Chiorino, Giovanna

    2016-01-01

    Adenocarcinomas of the prostate arise as multifocal heterogeneous lesions as the likely result of genetic and epigenetic alterations and deranged cell-cell communication. Notch signaling is an important form of intercellular communication with a role in growth/differentiation control and tumorigenesis. Contrasting reports exist in the literature on the role of this pathway in prostate cancer (PCa) development. We show here that i) compared to normal prostate tissue, Notch1 expression is significantly reduced in a substantial fraction of human PCas while it is unaffected or even increased in others; ii) acute Notch activation both inhibits and induces process networks associated with prostatic neoplasms; iii) down-modulation of Notch1 expression and activity in immortalized normal prostate epithelial cells increases their proliferation potential, while increased Notch1 activity in PCa cells suppresses growth and tumorigenicity through a Smad3-dependent mechanism involving p21WAF1/CIP1; iv) prostate cancer cells resistant to Notch growth inhibitory effects retain Notch1-induced upregulation of pro-oncogenic genes, like EPAS1 and CXCL6, also overexpressed in human PCas with high Notch1 levels. Taken together, these results reconcile conflicting data on the role of Notch1 in prostate cancer. PMID:27384993

  14. Dual tumor suppressing and promoting function of Notch1 signaling in human prostate cancer.

    PubMed

    Lefort, Karine; Ostano, Paola; Mello-Grand, Maurizia; Calpini, Valérie; Scatolini, Maria; Farsetti, Antonella; Dotto, G Paolo; Chiorino, Giovanna

    2016-07-26

    Adenocarcinomas of the prostate arise as multifocal heterogeneous lesions as the likely result of genetic and epigenetic alterations and deranged cell-cell communication. Notch signaling is an important form of intercellular communication with a role in growth/differentiation control and tumorigenesis. Contrasting reports exist in the literature on the role of this pathway in prostate cancer (PCa) development. We show here that i) compared to normal prostate tissue, Notch1 expression is significantly reduced in a substantial fraction of human PCas while it is unaffected or even increased in others; ii) acute Notch activation both inhibits and induces process networks associated with prostatic neoplasms; iii) down-modulation of Notch1 expression and activity in immortalized normal prostate epithelial cells increases their proliferation potential, while increased Notch1 activity in PCa cells suppresses growth and tumorigenicity through a Smad3-dependent mechanism involving p21WAF1/CIP1; iv) prostate cancer cells resistant to Notch growth inhibitory effects retain Notch1-induced upregulation of pro-oncogenic genes, like EPAS1 and CXCL6, also overexpressed in human PCas with high Notch1 levels. Taken together, these results reconcile conflicting data on the role of Notch1 in prostate cancer.

  15. Contractile properties of human prostate adenomas and the development of infravesical obstruction.

    PubMed

    Gup, D I; Shapiro, E; Baumann, M; Lepor, H

    1989-01-01

    The contractile response of human prostate adenomas to KCl, phenylephrine (alpha 1 adrenergic agonist), UK 14304 (alpha 2 adrenergic agonist), and carbachol (muscarinic cholinergic agonist) was evaluated in tissue specimens obtained from men with symptomatic and asymptomatic BPH. Prostate specimens were obtained from 5 men with asymptomatic BPH undergoing cystoprostatectomy, 11 men with symptomatic BPH undergoing open prostatectomy, and 11 men with symptomatic BPH undergoing transurethral resection of the prostate (TURP). Quantitative symptom score analysis and urinary flow rate determination documented the absence of bladder outlet obstruction in men undergoing cystoprostatectomy and confirmed the presence of bladder outlet obstruction in men undergoing prostatectomy. The magnitude of the contractile response (Emax) and the potency of phenylephrine-induced contractions (EC50) in prostatic preparations obtained from men with symptomatic and asymptomatic BPH were similar. The IC50 for the inhibition of phenylephrine-induced contractions by prazosin was 3.2 nM, confirming that phenylephrine-induced contraction in the human prostate is mediated by the alpha 1 adrenoceptor. The contractile responses of prostate adenomas to muscarinic cholinergic and alpha 2 agonists were negligible. This study demonstrates that the development of bladder outlet obstruction in men with BPH is not related to alterations in the functional response of the smooth muscle component of the prostate adenoma.

  16. Impact of interseed attenuation and tissue composition for permanent prostate implants

    SciTech Connect

    Carrier, Jean-Francois; Beaulieu, Luc; Therriault-Proulx, Francois; Roy, Rene

    2006-03-15

    The purpose is to evaluate the impact of interseed attenuation and prostate composition for prostate treatment plans with {sup 125}I permanent seed implants using the Monte Carlo (MC) method. The effect of seed density (number of seeds per prostate unit volume) is specifically investigated. The study focuses on treatment plans that were generated for clinical cases. For each plan, four different dose calculation techniques are compared: TG-43 based calculation, superposition MC, full MC with water prostate, and full MC with realistic prostate tissue. The prostate tissue description is from the ICRP report 23 (W. S. Snyer, M. J. Cook, E. S. Nasset, L. R. Karkhausen, G. P. Howells, and I. H. Tipton, ''Report of the task group on reference man,'' Technical Report 23, International Commission on Radiological Protection, 1974). According to the comparisons, the seed density has an influence on interseed attenuation. A plan with a typical low seed density (42 0.6 mCi seeds in a 26 cm{sup 3} prostate) suffers a 1.2% drop in the CTV D{sub 90} value due to interseed attenuation. A drop of 3.0% is calculated for a higher seed density (75 0.3 mCi seeds, same prostate). The influence of the prostate composition is similar for all seed densities and prostate sizes. The difference between MC simulations in water and MC simulations in prostate tissue is between 4.4% and 4.8% for the D{sub 90} parameter. Overall, the effect on D{sub 90} is ranging from 5.8% to 12.8% when comparing clinically approved TG-43 and MC simulations in prostate tissue. The impact varies from one patient to the other and depends on the prostate size and the number of seeds. This effect can reach a significant level when reporting correlations between clinical effect and deposited dose.

  17. Impact of interseed attenuation and tissue composition for permanent prostate implants.

    PubMed

    Carrier, Jean-François; Beaulieu, Luc; Therriault-Proulx, François; Roy, René

    2006-03-01

    The purpose is to evaluate the impact of interseed attenuation and prostate composition for prostate treatment plans with 125I permanent seed implants using the Monte Carlo (MC) method. The effect of seed density (number of seeds per prostate unit volume) is specifically investigated. The study focuses on treatment plans that were generated for clinical cases. For each plan, four different dose calculation techniques are compared: TG-43 based calculation, superposition MC, full MC with water prostate, and full MC with realistic prostate tissue. The prostate tissue description is from the ICRP report 23 (W. S. Snyer, M. J. Cook, E. S. Nasset, L. R. Karkhausen, G. P. Howells, and I. H. Tipton, "Report of the task group on reference man," Technical Report 23, International Commission on Radiological Protection, 1974). According to the comparisons, the seed density has an influence on interseed attenuation. A plan with a typical low seed density (42 0.6 mCi seeds in a 26 cm3 prostate) suffers a 1.2% drop in the CTV D90 value due to interseed attenuation. A drop of 3.0% is calculated for a higher seed density (75 0.3 mCi seeds, same prostate). The influence of the prostate composition is similar for all seed densities and prostate sizes. The difference between MC simulations in water and MC simulations in prostate tissue is between 4.4% and 4.8% for the D90 parameter. Overall, the effect on D90 is ranging from 5.8% to 12.8% when comparing clinically approved TG-43 and MC simulations in prostate tissue. The impact varies from one patient to the other and depends on the prostate size and the number of seeds. This effect can reach a significant level when reporting correlations between clinical effect and deposited dose.

  18. N-Myc Drives Neuroendocrine Prostate Cancer Initiated from Human Prostate Epithelial Cells.

    PubMed

    Lee, John K; Phillips, John W; Smith, Bryan A; Park, Jung Wook; Stoyanova, Tanya; McCaffrey, Erin F; Baertsch, Robert; Sokolov, Artem; Meyerowitz, Justin G; Mathis, Colleen; Cheng, Donghui; Stuart, Joshua M; Shokat, Kevan M; Gustafson, W Clay; Huang, Jiaoti; Witte, Owen N

    2016-04-11

    MYCN amplification and overexpression are common in neuroendocrine prostate cancer (NEPC). However, the impact of aberrant N-Myc expression in prostate tumorigenesis and the cellular origin of NEPC have not been established. We define N-Myc and activated AKT1 as oncogenic components sufficient to transform human prostate epithelial cells to prostate adenocarcinoma and NEPC with phenotypic and molecular features of aggressive, late-stage human disease. We directly show that prostate adenocarcinoma and NEPC can arise from a common epithelial clone. Further, N-Myc is required for tumor maintenance, and destabilization of N-Myc through Aurora A kinase inhibition reduces tumor burden. Our findings establish N-Myc as a driver of NEPC and a target for therapeutic intervention.

  19. N-Myc Drives Neuroendocrine Prostate Cancer Initiated from Human Prostate Epithelial Cells

    PubMed Central

    Lee, John K.; Phillips, John W.; Smith, Bryan A.; Park, Jung Wook; Stoyanova, Tanya; McCaffrey, Erin F.; Baertsch, Robert; Sokolov, Artem; Meyerowitz, Justin G.; Mathis, Colleen; Cheng, Donghui; Stuart, Joshua M.; Shokat, Kevan M.; Gustafson, W. Clay; Huang, Jiaoti; Witte, Owen N.

    2016-01-01

    SUMMARY MYCN amplification and overexpression are common in neuroendocrine prostate cancer (NEPC). However, the impact of aberrant N-Myc expression in prostate tumorigenesis and the cellular origin of NEPC have not been established. We define N-Myc and activated AKT1 as oncogenic components sufficient to transform human prostate epithelial cells to prostate adenocarcinoma and NEPC with phenotypic and molecular features of aggressive, late-stage human disease. We directly show that prostate adenocarcinoma and NEPC can arise from a common epithelial clone. Further, N-Myc is required for tumor maintenance and destabilization of N-Myc through Aurora A kinase inhibition reduces tumor burden. Our findings establish N-Myc as a driver of NEPC and a target for therapeutic intervention. PMID:27050099

  20. Molecular pathogenesis of human prostate basal cell hyperplasia.

    PubMed

    Henry, Gervaise; Malewska, Alicia; Mauck, Ryan; Gahan, Jeffrey; Hutchinson, Ryan; Torrealba, Jose; Francis, Franto; Roehrborn, Claus; Strand, Douglas

    2017-05-01

    Understanding the molecular pathogenesis of distinct phenotypes in human benign prostatic hyperplasia (BPH) is essential to improving therapeutic intervention. Current therapies target smooth muscle and luminal epithelia for relief of lower urinary tract symptoms (LUTS) due to BPH, but basal cell hyperplasia (BCH) remains untargeted. The incidence of has been reported at 8-10%, but a molecular and cellular characterization has not been performed on this phenotype. Using freshly digested tissue from surgical specimens, we performed RNA-seq analysis of flow cytometry-purified basal epithelia from 3 patients with and 4 patients without a majority BCH phenotype. qPCR was performed on 28 genes identified as significant from 13 non-BCH and 7 BCH specimens to confirm transcriptomic analysis. IHC was performed on several non-BCH and BCH specimens for 3 proteins identified as significant by transcriptomic analysis. A total of 141 human BPH specimens were analyzed for the presence of BCH. Clinical characteristics of non-BCH and BCH cohorts revealed no significant differences in age, PSA, prostate volume, medical treatment, or comorbidities. Quantitation of cellular subsets by flow cytometry in 11 BCH patients vs. 11 non-BCH patients demonstrated a significant increase in the ratio of basal to luminal epithelia in patients with BCH (P <0.05), but no significant differences in the total number of leukocytes. RNA-seq data from flow cytometry isolated basal epithelia from patients with and without BCH were subjected to gene set enrichment analysis of differentially expressed genes, which revealed increased expression of members of the epidermal differentiation complex. Transcriptomic data were complemented by immunohistochemistry for members of the epidermal differentiation complex, revealing a morphological similarity to other stratified squamous epithelial layers. Increased expression of epidermal differentiation complex members and altered epithelial stratification resembles

  1. Human Prostate Side Population Cells Demonstrate Stem Cell Properties in Recombination with Urogenital Sinus Mesenchyme

    PubMed Central

    Foster, Barbara A.; Gangavarapu, Kalyan J.; Mathew, Grinu; Azabdaftari, Gissou; Morrison, Carl D.; Miller, Austin; Huss, Wendy J.

    2013-01-01

    Stem cell enrichment provides a tool to examine prostate stem cells obtained from benign and malignant tissue. Functional assays can enrich stem cells based on common stem cell phenotypes, such as high ATP binding cassette (ABC) transporter mediated efflux of Hoechst substrates (side population assay). This functional assay is based upon mechanisms that protect cells from environmental insult thus contributing to the survival and protection of the stem cell population. We have isolated and analyzed cells digested from twelve clinical prostate specimens based on the side population assay. Prostate stem cell properties of the isolated cells were tested by serial recombination with rat urogenital mesenchyme. Recombinants with side population cells demonstrate an increase in the frequency of human ductal growth and the number of glands per recombinant when compared to recombinants with non-side population cells. Isolated cells were capable of prostatic growth for up to three generations in the recombination assay with as little as 125 sorted prostate cells. The ability to reproducibly use cells isolated by fluorescence activated cell sorting from human prostate tissue is an essential step to a better understanding of human prostate stem cell biology. ABC transporter G2 (ABCG2) was expressed in recombinants from side population cells indicating the side population cells have self-renewal properties. Epithelial cell differentiation of recombinants was determined by immunohistochemical analysis for expression of the basal, luminal, and neuroendocrine markers, p63, androgen receptor, prostate specific antigen, and chromogranin A, respectively. Thus, the ABCG2 expressing side population demonstrates multipotency and self-renewal properties indicating stem cells are within this population. PMID:23383057

  2. Emerging Roles of Human Prostatic Acid Phosphatase

    PubMed Central

    Kong, Hoon Young; Byun, Jonghoe

    2013-01-01

    Prostate cancer is one of the most prevalent non-skin related cancers. It is the second leading cause of cancer deaths among males in most Western countries. If prostate cancer is diagnosed in its early stages, there is a higher probability that it will be completely cured. Prostatic acid phosphatase (PAP) is a non-specific phosphomonoesterase synthesized in prostate epithelial cells and its level proportionally increases with prostate cancer progression. PAP was the biochemical diagnostic mainstay for prostate cancer until the introduction of prostate-specific antigen (PSA) which improved the detection of early-stage prostate cancer and largely displaced PAP. Recently, however, there is a renewed interest in PAP because of its usefulness in prognosticating intermediate to high-risk prostate cancers and its success in the immunotherapy of prostate cancer. Although PAP is believed to be a key regulator of prostate cell growth, its exact role in normal prostate as well as detailed molecular mechanism of PAP regulation is still unclear. Here, many different aspects of PAP in prostate cancer are revisited and its emerging roles in other environment are discussed. PMID:24009853

  3. The human (PEDB) and mouse (mPEDB) Prostate Expression Databases.

    PubMed

    Nelson, Peter S; Pritchard, Colin; Abbott, Denise; Clegg, Nigel

    2002-01-01

    The Prostate Expression Databases (PEDB and mPEDB) are online resources designed to allow researchers to access and analyze gene expression information derived from the human and murine prostate, respectively. Human PEDB archives more than 84 000 Expressed Sequence Tags (ESTs) from 38 prostate cDNA libraries in a curated relational database that provides detailed library information including tissue source, library construction methods, sequence diversity and sequence abundance. The differential expression of each EST species can be viewed across all libraries using a Virtual Expression Analysis Tool (VEAT), a graphical user interface written in Java for intra- and inter-library sequence comparisons. Recent enhancements to PEDB include (i) the development of a murine prostate expression database, mPEDB, that complements the human gene expression information in PEDB, (ii) the assembly of a non-redundant sequence set or 'prostate unigene' that represents the diversity of gene expression in the prostate, and (iii) an expanded search tool that supports both text-based and BLAST queries. PEDB and mPEDB are accessible via the World Wide Web at http://www.pedb.org and http://www.mpedb.org.

  4. Telocytes play a key role in prostate tissue organisation during the gland morphogenesis.

    PubMed

    Sanches, Bruno D A; Maldarine, Juliana S; Zani, Bruno C; Tamarindo, Guilherme H; Biancardi, Manoel F; Santos, Fernanda C A; Rahal, Paula; Góes, Rejane M; Felisbino, Sérgio L; Vilamaior, Patricia S L; Taboga, Sebastião R

    2017-08-24

    Telocytes are CD34-positive interstitial cells, known to exert several functions, one of which is a role in tissue organisation, previously demonstrated by telocytes in the myocardium. The existence of telocytes in the prostate has recently been reported, however, there is a lack of information regarding the function of these cells in prostate tissue, and information regarding the possible role of these cells in prostatic development. This study used immunofluorescence techniques in prostate tissue and prostatic telocytes in culture to determine the relationship between telocytes and prostate morphogenesis. Furthermore, immunofluorescent labelling of telocytes was performed on prostate tissue at different stages of early postnatal development. Initially, CD34-positive cells are found at the periphery of the developing alveoli, later in the same region, c-kit-positive cells and cells positive for both factors are verified and CD34-positive cells were predominantly observed in the interalveolar stroma and the region surrounding the periductal smooth muscle. Fluorescence assays also demonstrated that telocytes secrete TGF-β1 and are ER-Beta (ERβ) positive. The results suggest that telocytes play a changing role during development, initially supporting the differentiation of periductal and perialveolar smooth muscle, and later, producing dense networks that separate alveoli groups and form a barrier between the interalveolar region and periurethral smooth muscle. We conclude that telocytes play a relevant role in prostate tissue organisation during postnatal development. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  5. Discovery of Hyperpolarized Molecular Imaging Biomarkers in a Novel Prostate Tissue Slice Culture Model

    DTIC Science & Technology

    2013-06-01

    compatible bioreactor and that hyperpolarized 13C spectroscopy could be employed to study real-time metabolism of normal and malignant tissues. The...function of prostate tissue slice cultures (TCSs) in an nuclear magnetic resonance (NMR)-compatible, 3-dimensional tissue culture bioreactor , (2) to use...the TSC/NMR bioreactor model to identify hyperpolarized metabolic biomarkers of prostate cancer presence and aggressiveness, and (3) to use the TSC

  6. Lack of detection of human papillomavirus DNA in prostate carcinomas in patients from northeastern Brazil

    PubMed Central

    Araujo-Neto, Ari P.; Ferreira-Fernandes, Hygor; Amaral, Carolina M.M.; Santos, Lina G.; Freitas, Antônio C.; Silva-Neto, Jacinto C.; Rey, Juan A.; Burbano, Rommel R.; da Silva, Benedito B.; Yoshioka, France K.N.; Pinto, Giovanny R.

    2016-01-01

    Abstract Prostate cancer is the second most common cancer among men in western populations, and despite its high mortality, its etiology remains unknown. Inflammatory processes are related to the etiology of various types of tumors, and prostate inflammation, in particular, has been associated with prostate cancer carcinogenesis and progression. Human papillomavirus (HPV) is associated with benign and malignant lesions in the anogenital tract of both females and males. The possible role of HPV in prostate carcinogenesis is a subject of great controversy. In this study, we aimed to examine the prevalence of HPV infections in prostate carcinomas of patients from northeastern Brazil. This study included 104 tissue samples from primary prostate carcinoma cases. HPV DNA was purified and then amplified using MY09/11 and GP5+/GP6+ degenerate primer sets that detect a wide range of HPV types, and with specific PCR primers sets for E6 and E7 HPV regions to detect HPV 16. None of the samples showed amplification products of HPV DNA for primer sets MY09/11 and GP5+/GP6+, or the specific primer set for the E6 and E7 HPV regions. HPV infection, thus, does not seem to be one of the causes of prostate cancer in the population studied. PMID:27007894

  7. Lack of detection of human papillomavirus DNA in prostate carcinomas in patients from northeastern Brazil.

    PubMed

    Araujo-Neto, Ari P; Ferreira-Fernandes, Hygor; Amaral, Carolina M M; Santos, Lina G; Freitas, Antônio C; Silva-Neto, Jacinto C; Rey, Juan A; Burbano, Rommel R; Silva, Benedito B da; Yoshioka, France K N; Pinto, Giovanny R

    2016-03-01

    Prostate cancer is the second most common cancer among men in western populations, and despite its high mortality, its etiology remains unknown. Inflammatory processes are related to the etiology of various types of tumors, and prostate inflammation, in particular, has been associated with prostate cancer carcinogenesis and progression. Human papillomavirus (HPV) is associated with benign and malignant lesions in the anogenital tract of both females and males. The possible role of HPV in prostate carcinogenesis is a subject of great controversy. In this study, we aimed to examine the prevalence of HPV infections in prostate carcinomas of patients from northeastern Brazil. This study included 104 tissue samples from primary prostate carcinoma cases. HPV DNA was purified and then amplified using MY09/11 and GP5+/GP6+ degenerate primer sets that detect a wide range of HPV types, and with specific PCR primers sets for E6 and E7 HPV regions to detect HPV 16. None of the samples showed amplification products of HPV DNA for primer sets MY09/11 and GP5+/GP6+, or the specific primer set for the E6 and E7 HPV regions. HPV infection, thus, does not seem to be one of the causes of prostate cancer in the population studied.

  8. Neural protein gamma-synuclein interacting with androgen receptor promotes human prostate cancer progression

    PubMed Central

    2012-01-01

    Background Gamma-synuclein (SNCG) has previously been demonstrated to be significantly correlated with metastatic malignancies; however, in-depth investigation of SNCG in prostate cancer is still lacking. In the present study, we evaluated the role of SNCG in prostate cancer progression and explored the underlying mechanisms. Methods First, alteration of SNCG expression in LNCaP cell line to test the ability of SNCG on cellular properties in vitro and vivo whenever exposing with androgen or not. Subsequently, the Dual-luciferase reporter assays were performed to evaluate whether the role of SNCG in LNCaP is through AR signaling. Last, the association between SNCG and prostate cancer progression was assessed immunohistochemically using a series of human prostate tissues. Results Silencing SNCG by siRNA in LNCaP cells contributes to the inhibition of cellular proliferation, the induction of cell-cycle arrest at the G1 phase, the suppression of cellular migration and invasion in vitro, as well as the decrease of tumor growth in vivo with the notable exception of castrated mice. Subsequently, mechanistic studies indicated that SNCG is a novel androgen receptor (AR) coactivator. It interacts with AR and promotes prostate cancer cellular growth and proliferation by activating AR transcription in an androgen-dependent manner. Finally, immunohistochemical analysis revealed that SNCG was almost undetectable in benign or androgen-independent tissues prostate lesions. The high expression of SNCG is correlated with peripheral and lymph node invasion. Conclusions Our data suggest that SNCG may serve as a biomarker for predicting human prostate cancer progression and metastasis. It also may become as a novel target for biomedical therapy in advanced prostate cancer. PMID:23231703

  9. A Vector-Based Short Hairpin RNA Targeting Aurora B Suppresses Human Prostatic Carcinoma Growth.

    PubMed

    Cao, Mei; Qi, Panpan; Chen, Chong; Song, Liju; Wang, Xuege; Li, Ningzhe; Wu, Daoyan; Hu, Guoku; Zhao, Jian

    2017-02-01

    Aurora kinase B, playing a vital, important role in mitosis, is frequently detected to be overexpressed in many cancer cell lines and various tumor tissues, including prostatic carcinoma. Given the essential function of Aurora kinase B in mitosis and its association with tumorigenesis, it might be a drug target for prostatic carcinoma treatment. In our study, short hairpin RNA targeting Aurora kinase B was cloned into a pGPU6 plasmid vector and then transfected into human prostatic carcinoma cells. The expression level of Aurora kinase B was verified by reverse transcription-polymerase chain reaction and Western blot. At the same time, cell apoptosis was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide, fluorescent staining, and flow cytometric analysis. Furthermore, prostate carcinoma cells were injected into mice to establish a tumor xenograft model. Previous studies have shown the effect of pGPU6-shAURKB plasmid on tumor growth in a prostate carcinoma xenogenic implantation model. From the study, we knew that the Aurora kinase B was significantly downregulated in prostate carcinoma cells, and cell apoptosis was also detected higher in treated groups than that in control groups. Moreover, in the prostate carcinoma xenogenic implantation model, compared with the control groups, the tumor growth was inhibited about 78.7% in the pGPU6-shAURKB plasmid-treated group, and cell apoptosis in the experimental group was notably higher than that in control groups. The average duration of tumor-bearing mice was prolonged to about 35 days. The results of experiment indicated that specific knockdown of Aurora kinase B led to prostate carcinoma cells apoptosis and inhibited tumor growth. Our data clearly confirmed that specific knockdown of Aurora kinase B expression by vector-based short hairpin RNA/liposome may be a potential new approach to treat human prostatic carcinoma.

  10. Mitogenic activation of human prostate-derived fibromuscular stromal cells by bradykinin

    PubMed Central

    Walden, Paul D; Lefkowitz, Gary K; Ittmann, Michael; Lepor, Herbert; Monaco, Marie E

    1999-01-01

    Biologically active kinin peptides are released from precursor kininogens by kallikreins. Kinins act on kinin receptors to mediate diverse biological functions including smooth muscle contraction, inflammation, pain and mitogenicity. All components of the kallikrein-kinin system exist in human male genital secretions suggesting that these molecules participate in physiological and pathophysiological genitourinary function. The objective of this study was to assess the consequences of kinin action on prostate cells.Primary cultures of prostate secretory epithelial (PE) and prostate fibromuscular stromal (PS) cells were established from human prostate tissue. Transcripts encoding both the human B1 and B2 bradykinin receptor subtypes were detected in human prostate transition-zone tissue and in cultured cells by RT–PCR. In receptor binding assays, the B1 subtype predominated on PE cell membranes and the B2 subtype predominated on PS cell membranes. In PS cells, but not in PE cells, BK induced significant inositol phosphate accumulation and [3H]-thymidine uptake. These responses were mediated through the B2 receptor subtype.The use of signal transduction inhibitors indicated that mitogenic activation by BK occurred through both protein kinase C (PKC) and protein tyrosine kinase dependent mechanisms. PMA (phorbol 12-myristate 13-acetate) produced maximal [3H]-thymidine uptake by PS cells, resulted in cell elongation and caused the α-actin fibres present in PS smooth muscle cells to became organized into parallel arrays along the length of the elongated cells.In summary, the prostate contains a functional kallikrein-kinin system, which could be significant in physiological and pathophysiological prostate function. PMID:10369476

  11. Upregulation of minichromosome maintenance complex component 3 during epithelial-to-mesenchymal transition in human prostate cancer.

    PubMed

    Stewart, Paul A; Khamis, Zahraa I; Zhau, Haiyen E; Duan, Peng; Li, Quanlin; Chung, Leland W K; Sang, Qing-Xiang Amy

    2017-06-13

    Metastasis is often associated with epithelial-to-mesenchymal transition (EMT). To understand the molecular mechanisms of this process, we conducted proteomic analysis of androgen-repressed cancer of the prostate (ARCaP), an experimental model of metastatic human prostate cancer. The protein signatures of epithelial (ARCaPE) and mesenchymal (ARCaPM) cells were consistent with their phenotypes. Importantly, the expression of mini-chromosome maintenance 3 (MCM3) protein, a crucial subunit of DNA helicase, was significantly higher in ARCaPM cells than that of ARCaPE cells. This increased MCM3 protein expression level was verified using Western blot analysis of the ARCaP cell lineages. Furthermore, immunohistochemical analysis of MCM3 protein levels in human prostate tissue specimens showed elevated expression in bone metastasis and advanced human prostate cancer tissue samples. Subcutaneous injection experiments using ARCaPE and ARCaPM cells in a mouse model also revealed increased MCM3 protein levels in mesenchymal-derived tumors. This study identifies MCM3 as an upregulated molecule in mesenchymal phenotype of human prostate cancer cells and advanced human prostate cancer specimens, suggesting MCM3 may be a new potential drug target for prostate cancer treatment.

  12. Epigenomic profiling of DNA methylation in paired prostate cancer versus adjacent benign tissue.

    PubMed

    Geybels, Milan S; Zhao, Shanshan; Wong, Chao-Jen; Bibikova, Marina; Klotzle, Brandy; Wu, Michael; Ostrander, Elaine A; Fan, Jian-Bing; Feng, Ziding; Stanford, Janet L

    2015-12-01

    Aberrant DNA methylation may promote prostate carcinogenesis. We investigated epigenome-wide DNA methylation profiles in prostate cancer (PCa) compared to adjacent benign tissue to identify differentially methylated CpG sites. The study included paired PCa and adjacent benign tissue samples from 20 radical prostatectomy patients. Epigenetic profiling was done using the Infinium HumanMethylation450 BeadChip. Linear models that accounted for the paired study design and False Discovery Rate Q-values were used to evaluate differential CpG methylation. mRNA expression levels of the genes with the most differentially methylated CpG sites were analyzed. In total, 2,040 differentially methylated CpG sites were identified in PCa versus adjacent benign tissue (Q-value < 0.001), the majority of which were hypermethylated (n = 1,946; 95%). DNA methylation profiles accurately distinguished between PCa and benign tissue samples. Twenty-seven top-ranked hypermethylated CpGs had a mean methylation difference of at least 40% between tissue types, which included 25 CpGs in 17 genes. Furthermore, for 10 genes over 50% of promoter region CpGs were hypermethylated in PCa versus benign tissue. The top-ranked differentially methylated genes included three genes that were associated with both promoter hypermethylation and reduced gene expression: SCGB3A1, HIF3A, and AOX1. Analysis of The Cancer Genome Atlas (TCGA) data provided confirmatory evidence for our findings. This study of PCa versus adjacent benign tissue showed many differentially methylated CpGs and regions in and outside gene promoter regions, which may potentially be used for the development of future epigenetic-based diagnostic tests or as therapeutic targets. © 2015 Wiley Periodicals, Inc.

  13. Breaking through a roadblock in prostate cancer research: an update on human model systems.

    PubMed

    Toivanen, R; Taylor, R A; Pook, D W; Ellem, S J; Risbridger, G P

    2012-09-01

    Prostate cancer is a prevalent disease that affects the aging male population. Whilst there have been significant advances of our biological understanding of the disease, clinical translation of promising agents continues to lag behind. In part, this is due to a paucity of relevant experimental and pre-clinical models required to further develop effective prevention and therapeutic strategies. Genetically modified cell lines fail to entirely represent the genetic and molecular diversity of primary human specimens, particularly from localised disease. Furthermore, primary prostate cancer tissues are extremely difficult to grow in the laboratory and virtually all human models, whether they grow as xenografts in immune-deficient animals or as cell cultures, are genetically modified by the investigator or derived from patients with advanced metastatic disease. In this review, we discuss the latest advances and improvements to current methods of xenografting human primary prostate cancer, and their potential application to translational research.

  14. Hyperspectral stimulated Raman scattering imaging facilitates accurate diagnosis of human prostate cancer

    NASA Astrophysics Data System (ADS)

    Cui, Sishan; Wang, Ping; Yue, Shuhua

    2017-02-01

    Due to the subject nature of histopathology, there is a significant inter-observer discordance for the differentiation between low-risk prostate cancer (Gleason score <= 6), which can be left without treatment, and high-risk prostate cancer (Gleason score >6), which requires active treatment. Our previous study using Raman spectromicroscopy reveals that cholesteryl ester accumulation underlies human prostate cancer aggressiveness. However, Raman spectromicroscopy could only provide compositional information of certain lipid droplets of interest, which overlooked cell-to-cell variation and hindered translation to accurate automated diagnosis. Here, we demonstrated quantitative mapping of cholesteryl ester molar percentage in human prostate cancer tissues using hyperspectral stimulated Raman scattering microscopy that renders compositional information for every pixel in the image. Specifically, hundreds of SRS images at Raman shift between 2800 3000 cm-1 were taken, and multivariate curve resolution algorism was used to retrieve concentration images of lipid, lipofuscin, and protein. We found that the height ratio between the prominent cholesterol band at 2870 cm-1 and the CH2 stretching band at 2850 cm-1 was proportional to the molar percentage of cholesteryl ester present in the total lipids. Based on the calibration curve, we were able to quantitatively map cholesteryl ester level in intact prostate cancer tissues. Our data showed that not only the amount of cholesteryl ester-rich lipid droplets, but also the CE molar percentage, was significantly greater in prostate cancer tissues with Gleason score > 6 compared to the ones with Gleason score <= 6. Our study offers an opportunity towards more accurate prostate cancer diagnosis.

  15. Acoustic radiation force impulse imaging of human prostates: initial in vivo demonstration.

    PubMed

    Zhai, Liang; Polascik, Thomas J; Foo, Wen-Chi; Rosenzweig, Stephen; Palmeri, Mark L; Madden, John; Nightingale, Kathryn R

    2012-01-01

    Reliably detecting prostate cancer (PCa) has been a challenge for current imaging modalities. Acoustic radiation force impulse (ARFI) imaging is an elasticity imaging method that uses remotely generated, focused acoustic beams to probe tissue stiffness. A previous study on excised human prostates demonstrated ARFI images portray various prostatic structures and has the potential to guide prostate needle biopsy with improved sampling accuracy. The goal of this study is to demonstrate the feasibility of ARFI imaging to portray internal structures and PCa in the human prostate in vivo. Custom ARFI imaging sequences were designed and implemented using a modified Siemens Antares™ scanner with a three-dimensional (3-D) wobbler, end-firing, trans-cavity transducer, EV9F4. Nineteen patients were consented and imaged immediately preceding surgical prostatectomy. Pathologies and anatomic structures were identified in histologic slides by a pathologist blinded to ARFI data and were then registered with structures found in ARFI images. The results demonstrated that when PCa is visible, it generally appears as bilaterally asymmetric stiff structures; benign prostatic hyperplasia (BPH) appears heterogeneous with a nodular texture; the verumontanum and ejaculatory ducts appears softer compared with surrounding tissue, which form a unique 'V' shape; and the boundary of the transitional zone (TZ) forms a stiff rim separating the TZ from the peripheral zone (PZ). These characteristic appearances of prostatic structures are consistent with those found in our previous study of prostate ARFI imaging on excised human prostates. Compared with the matched B-mode images, ARFI images, in general, portray prostate structures with higher contrast. With the end-firing transducer used for this study, ARFI depth penetration was limited to 22 mm. Image contrast and resolution were decreased as compared with the previous ex vivo study due to the small transducer aperture. Even with these

  16. Prostate tissue ablation with MRI guided transurethral therapeutic ultrasound and intraoperative assessment of the integrity of the neurovascular bundle

    NASA Astrophysics Data System (ADS)

    Sammet, Steffen; Partanen, Ari; Yousuf, Ambereen; Wardrip, Craig; Niekrasz, Marek; Antic, Tatjana; Razmaria, Aria; Sokka, Sham; Karczmar, Gregory; Oto, Aytekin

    2017-03-01

    demonstrates the effectiveness and precision of transurethral ultrasound ablation of prostatic tissue in canines with MRI monitoring and guidance. The canine prostate is an excellent model for the human prostate with similar anatomical characteristics and diseases. MRI guidance with real-time, intraoperative temperature monitoring reduces the risk of damaging critical surrounding anatomical structures in ultrasound therapy of the prostate.

  17. Targeting tissue factor on tumor vascular endothelial cells and tumor cells for immunotherapy in mouse models of prostatic cancer.

    PubMed

    Hu, Z; Garen, A

    2001-10-09

    The efficacy and safety of an immunoconjugate (icon) molecule, composed of a mutated mouse factor VII (mfVII) targeting domain and the Fc effector domain of an IgG1 Ig (mfVII/Fc icon), was tested with a severe combined immunodeficient (SCID) mouse model of human prostatic cancer and an immunocompetent mouse model of mouse prostatic cancer. The SCID mice were first injected s.c. with a human prostatic tumor line, forming a skin tumor that produces a high blood titer of prostate-specific antigen and metastasizes to bone. The icon was encoded in a replication-incompetent adenoviral vector that was injected directly into the skin tumor. The tumor cells infected by the vector synthesize and secrete the icon into the blood, and the blood-borne icon binds with high affinity and specificity to mouse tissue factor expressed on endothelial cells lining the lumen of the tumor vasculature and to human tissue factor expressed on the tumor cells. The Fc domain of the icon activates a cytolytic immune attack against cells that bind the icon. The immunotherapy tests in SCID mice demonstrated that intratumoral injections of the adenoviral vector encoding the mfVII/human Fc icon resulted in long-term regression of the injected human prostatic tumor and also of a distant uninjected tumor, without associated toxicity to the mice. Comparable results were obtained with a SCID mouse model of human melanoma. At the end of the experiments the mice appeared to be free of viable tumor cells. This protocol also could be efficacious for treating cancer patients who have vascularized tumors.

  18. Determination of optical coefficients and fractal dimensional parameters of cancerous and normal prostate tissues.

    PubMed

    Pu, Yang; Wang, Wubao; Al-Rubaiee, Mohammad; Gayen, Swapan Kumar; Xu, Min

    2012-07-01

    Optical extinction and diffuse reflection spectra of cancerous and normal prostate tissues in the 750 to 860 nm spectral range were measured. Optical extinction measurements using thin ex vivo prostate tissue samples were used to determine the scattering coefficient (μ(s)), while diffuse reflection measurements using thick prostate tissue samples were used to extract the absorption coefficient (μ(a)) and the reduced scattering coefficient (μ'(s)). The anisotropy factor (g) was obtained using the extracted values of μ(s) and μ'(s). The values of fractal dimension (D(f)) of cancerous and normal prostate tissues were obtained by fitting to the wavelength dependence of μ'(s). The number of scattering particles contributing to μ(s) as a function of particle size and the cutoff diameter d(max) as a function of g were investigated using the fractal soft tissue model and Mie theory. Results show that d(max) of the normal tissue is larger than that of the cancerous tissue. The cutoff diameter d(max) is observed to agree with the nuclear size for the normal tissues and the nucleolar size for the cancerous tissues. Transmission spectral polarization imaging measurements were performed that could distinguish the cancerous prostate tissue samples from the normal tissue samples based on the differences between their absorption and scattering parameters.

  19. Expression of peroxisome proliferator-activated receptor (PPAR) in human prostate cancer.

    PubMed

    Segawa, Yoshihiro; Yoshimura, Rikio; Hase, Taro; Nakatani, Tatsuya; Wada, Seiji; Kawahito, Yutaka; Kishimoto, Taketoshi; Sano, Hajime

    2002-05-01

    Recent studies have demonstrated that peroxisome proliferator activator-receptors (PPAR)-gamma is expressed in some cancer cells such as breast, lung, and gastric cancer, and its ligand induces growth arrest of these cancer cells through apoptosis. However, the expression and localization of PPARs in prostate have not been examined. In this study, PPARs expression was investigated in human prostate cancer (PC), prostatic intraepithelial neoplasia (PIN), benign prostatic hyperplasia (BPH), and normal prostate (NP) tissues. Tumor specimens were obtained from 156 patients with PC, 15 with PIN, 20 with BPH, and 12 patients with NP tissues. The expressions were investigated by RT-PCR and immunohistochemical methods. Immunoreactive PPAR-alpha and -beta were significantly apparent in PC tissues. Marked expressions of PPAR-alpha and -beta were also detected in PIN, BPH, and NP groups. However, very weak or no expression of immunoreactive PPAR-gamma was found in BPH and NP cases. In contrast, we found significant expression of immunoreactive PPAR-gamma in cancer cells in PC group and in PIN group. Our results demonstrated that PPAR-gamma is induced in PC, and suggest that PPAR-gamma ligands may mediate its own potent antiproliferative effect against PC cells through differentiation. Copyright 2002 Wiley-Liss, Inc.

  20. The Isolation and Characterization of Human Prostate Cancer Stem Cells

    DTIC Science & Technology

    2015-05-01

    following significant findings/observations: i) 3D culture of human prostate cancer cells with magnetic nanoparticles is not optimal for tumor initiation...include: magnetic nanoparticles and using a stable (non-transformed) human prostate fibroblast cell line as a feeder layer. The former uses inert magnetic... nanoparticles (3D Biosciences, Inc.) that passively diffuse into live cells that then allow 3D growth in an applied magnetic field1. Such a

  1. Gene expression profile of mouse prostate tumors reveals dysregulations in major biological processes and identifies potential murine targets for preclinical development of human prostate cancer therapy.

    PubMed

    Haram, Kerstyn M; Peltier, Heidi J; Lu, Bin; Bhasin, Manoj; Otu, Hasan H; Choy, Bob; Regan, Meredith; Libermann, Towia A; Latham, Gary J; Sanda, Martin G; Arredouani, Mohamed S

    2008-10-01

    Translation of preclinical studies into effective human cancer therapy is hampered by the lack of defined molecular expression patterns in mouse models that correspond to the human counterpart. We sought to generate an open source TRAMP mouse microarray dataset and to use this array to identify differentially expressed genes from human prostate cancer (PCa) that have concordant expression in TRAMP tumors, and thereby represent lead targets for preclinical therapy development. We performed microarrays on total RNA extracted and amplified from eight TRAMP tumors and nine normal prostates. A subset of differentially expressed genes was validated by QRT-PCR. Differentially expressed TRAMP genes were analyzed for concordant expression in publicly available human prostate array datasets and a subset of resulting genes was analyzed by QRT-PCR. Cross-referencing differentially expressed TRAMP genes to public human prostate array datasets revealed 66 genes with concordant expression in mouse and human PCa; 56 between metastases and normal and 10 between primary tumor and normal tissues. Of these 10 genes, two, Sox4 and Tubb2a, were validated by QRT-PCR. Our analysis also revealed various dysregulations in major biologic pathways in the TRAMP prostates. We report a TRAMP microarray dataset of which a gene subset was validated by QRT-PCR with expression patterns consistent with previous gene-specific TRAMP studies. Concordance analysis between TRAMP and human PCa associated genes supports the utility of the model and suggests several novel molecular targets for preclinical therapy.

  2. Endocrine Disruption and Human Prostate Cancer

    DTIC Science & Technology

    2008-03-01

    described in Task 1, was to expose pregnant female rats to vinclozolin and test if the inductive and instructive properties of the prostate stroma is...ethane dimethane sulphonate ) during sexual differentiation produces diverse profiles of reproductive malformations in the male rat. Toxicol Ind Health...BPH Benign prostate hyperplasia cDNA Complementary deoxyribonucleic acid DP Dorsal prostate EDC Endocrine disruptor E Estrogen FgF10

  3. Magnetic resonance microscopy of prostate tissue: How basic science can inform clinical imaging development

    SciTech Connect

    Bourne, Roger

    2013-03-15

    This commentary outlines how magnetic resonance imaging (MRI) microscopy studies of prostate tissue samples and whole organs have shed light on a number of clinical imaging mysteries and may enable more effective development of new clinical imaging methods.

  4. Boosting antitumor responses of T lymphocytes infiltrating human prostate cancers

    PubMed Central

    Bronte, Vincenzo; Kasic, Tihana; Gri, Giorgia; Gallana, Keti; Borsellino, Giovanna; Marigo, Ilaria; Battistini, Luca; Iafrate, Massimo; Prayer-Galetti, Tommaso; Pagano, Francesco; Viola, Antonella

    2005-01-01

    Immunotherapy may provide valid alternative therapy for patients with hormone-refractory metastatic prostate cancer. However, if the tumor environment exerts a suppressive action on antigen-specific tumor-infiltrating lymphocytes (TIL), immunotherapy will achieve little, if any, success. In this study, we analyzed the modulation of TIL responses by the tumor environment using collagen gel matrix–supported organ cultures of human prostate carcinomas. Our results indicate that human prostatic adenocarcinomas are infiltrated by terminally differentiated cytotoxic T lymphocytes that are, however, in an unresponsive status. We demonstrate the presence of high levels of nitrotyrosines in prostatic TIL, suggesting a local production of peroxynitrites. By inhibiting the activity of arginase and nitric oxide synthase, key enzymes of L-arginine metabolism that are highly expressed in malignant but not in normal prostates, reduced tyrosine nitration and restoration of TIL responsiveness to tumor were achieved. The metabolic control exerted by the tumor on TIL function was confirmed in a transgenic mouse prostate model, which exhibits similarities with human prostate cancer. These results identify a novel and dominant mechanism by which cancers induce immunosuppression in situ and suggest novel strategies for tumor immunotherapy. PMID:15824085

  5. Boosting antitumor responses of T lymphocytes infiltrating human prostate cancers.

    PubMed

    Bronte, Vincenzo; Kasic, Tihana; Gri, Giorgia; Gallana, Keti; Borsellino, Giovanna; Marigo, Ilaria; Battistini, Luca; Iafrate, Massimo; Prayer-Galetti, Tommaso; Pagano, Francesco; Viola, Antonella

    2005-04-18

    Immunotherapy may provide valid alternative therapy for patients with hormone-refractory metastatic prostate cancer. However, if the tumor environment exerts a suppressive action on antigen-specific tumor-infiltrating lymphocytes (TIL), immunotherapy will achieve little, if any, success. In this study, we analyzed the modulation of TIL responses by the tumor environment using collagen gel matrix-supported organ cultures of human prostate carcinomas. Our results indicate that human prostatic adenocarcinomas are infiltrated by terminally differentiated cytotoxic T lymphocytes that are, however, in an unresponsive status. We demonstrate the presence of high levels of nitrotyrosines in prostatic TIL, suggesting a local production of peroxynitrites. By inhibiting the activity of arginase and nitric oxide synthase, key enzymes of L-arginine metabolism that are highly expressed in malignant but not in normal prostates, reduced tyrosine nitration and restoration of TIL responsiveness to tumor were achieved. The metabolic control exerted by the tumor on TIL function was confirmed in a transgenic mouse prostate model, which exhibits similarities with human prostate cancer. These results identify a novel and dominant mechanism by which cancers induce immunosuppression in situ and suggest novel strategies for tumor immunotherapy.

  6. Agonist and antagonist switch DNA motifs recognized by human androgen receptor in prostate cancer

    PubMed Central

    Chen, Zhong; Lan, Xun; Thomas-Ahner, Jennifer M; Wu, Dayong; Liu, Xiangtao; Ye, Zhenqing; Wang, Liguo; Sunkel, Benjamin; Grenade, Cassandra; Chen, Junsheng; Zynger, Debra L; Yan, Pearlly S; Huang, Jiaoti; Nephew, Kenneth P; Huang, Tim H-M; Lin, Shili; Clinton, Steven K; Li, Wei; Jin, Victor X; Wang, Qianben

    2015-01-01

    Human transcription factors recognize specific DNA sequence motifs to regulate transcription. It is unknown whether a single transcription factor is able to bind to distinctly different motifs on chromatin, and if so, what determines the usage of specific motifs. By using a motif-resolution chromatin immunoprecipitation-exonuclease (ChIP-exo) approach, we find that agonist-liganded human androgen receptor (AR) and antagonist-liganded AR bind to two distinctly different motifs, leading to distinct transcriptional outcomes in prostate cancer cells. Further analysis on clinical prostate tissues reveals that the binding of AR to these two distinct motifs is involved in prostate carcinogenesis. Together, these results suggest that unique ligands may switch DNA motifs recognized by ligand-dependent transcription factors in vivo. Our findings also provide a broad mechanistic foundation for understanding ligand-specific induction of gene expression profiles. PMID:25535248

  7. Discovery of Hyperpolarized Molecular Imaging Biomarkers in a Novel Prostate Tissue Slice Culture Model

    DTIC Science & Technology

    2013-06-01

    compatible bioreactor optimized in year 1 to identify hyperpolarized metabolic biomarkers of prostate cancer presence and aggressiveness. To...accomplish this goal my group finished the engineering of a 5 mm bioreactor and acquired hyperpolarized [1-13C]pyruvate data indicating that similar signal...to noise and quality data can be achieved with 4 to 5 prostate tissue slices in the 5 mm bioreactor as was acquired from 30-40 tissue slices in the

  8. Ghrelin O-acyltransferase (GOAT) is expressed in prostate cancer tissues and cell lines and expression is differentially regulated in vitro by ghrelin

    PubMed Central

    2013-01-01

    Background Ghrelin is a 28 amino acid peptide hormone that is expressed in the stomach and a range of peripheral tissues, where it frequently acts as an autocrine/paracrine growth factor. Ghrelin is modified by a unique acylation required for it to activate its cognate receptor, the growth hormone secretagogue receptor (GHSR), which mediates many of the actions of ghrelin. Recently, the enzyme responsible for adding the fatty acid residue (octanoyl/acyl group) to the third amino acid of ghrelin, GOAT (ghrelin O-acyltransferase), was identified. Methods We used cell culture, quantitative real-time reverse transcription (RT)-PCR and immunohistochemistry to demonstrate the expression of GOAT in prostate cancer cell lines and tissues from patients. Real-time RT-PCR was used to demonstrate the expression of prohormone convertase (PC)1/3, PC2 and furin in prostate cancer cell lines. Prostate-derived cell lines were treated with ghrelin and desacyl ghrelin and the effect on GOAT expression was measured using quantitative RT-PCR. Results We have demonstrated that GOAT mRNA and protein are expressed in the normal prostate and human prostate cancer tissue samples. The RWPE-1 and RWPE-2 normal prostate-derived cell lines and the LNCaP, DU145, and PC3 prostate cancer cell lines express GOAT and at least one other enzyme that is necessary to produce mature, acylated ghrelin from proghrelin (PC1/3, PC2 or furin). Finally, ghrelin, but not desacyl ghrelin (unacylated ghrelin), can directly regulate the expression of GOAT in the RWPE-1 normal prostate derived cell line and the PC3 prostate cancer cell line. Ghrelin treatment (100nM) for 6 hours significantly decreased GOAT mRNA expression two-fold (P < 0.05) in the PC3 prostate cancer cell line, however, ghrelin did not regulate GOAT expression in the DU145 and LNCaP prostate cancer cell lines. Conclusions This study demonstrates that GOAT is expressed in prostate cancer specimens and cell lines. Ghrelin regulates GOAT

  9. Positive correlation between PEDF expression levels and macrophage density in the human prostate

    PubMed Central

    Nelius, Thomas; Samathanam, Christina; Martinez-Marin, Dalia; Gaines, Natalie; Stevens, Jessica; Hickson, Johnny; de Riese, Werner; Filleur, Stéphanie

    2012-01-01

    BACKGROUND In this study, we investigated the capacity of PEDF to modulate the recruitment and the differentiation of monocytes/macrophages both in vitro and in human prostate. METHODS Using Boyden chambers, we assessed PEDF effect on the migration of monocytes and chemically-activated RAW264.7 macrophages. Normal, prostatitis and prostate cancer specimens were retrospectively selected and examined by immunohistochemistry for PEDF expression and infiltration of immune CD68+macrophagic cells. PEDF expression and macrophage density were then correlated with each other and clinicopathological parameters. M1 and M2 differentiation markers were quantified by qRT-PCR, western blotting and ELISA. RESULTS In chemotaxis, PEDF induced the migration of monocytes/macrophages. In immunohistochemistry, macrophages were markedly increased in prostatitis and malignant compared to normal tissues. PEDF was expressed at variable levels in the stroma and epithelium. PEDF mRNA was down-regulated in both prostate cancer and prostatitis compared to normal tissues. In correlation studies, macrophage density and PEDF expression were respectively positively and negatively associated with prostate size. Most importantly, PEDF expression positively correlated with macrophage density. Finally, PEDF stimulated the expression of iNOS, IL12 and TNFα; and inhibited IL10 and arginase 1 in mouse and human macrophages confirming a M1-type differentiation. CONCLUSIONS Our data demonstrate that PEDF acts directly on monocytes/macrophages by inducing their migration and differentiation into M1-type cells. These findings suggest a possible role of macrophages in PEDF anti-tumor properties and may support further development of PEDF-based anti-cancer therapy. PMID:23038613

  10. Phenotypic characterization of telomerase-immortalized primary non-malignant and malignant tumor-derived human prostate epithelial cell lines

    SciTech Connect

    Gu Yongpeng; Li Hongzhen; Miki, Jun; Kim, Kee-Hong; Furusato, Bungo; Sesterhenn, Isabell A.; Chu, Wei-Sing; McLeod, David G.; Srivastava, Shiv; Ewing, Charles M.; Isaacs, William B.; Rhim, Johng S. . E-mail: jrhim@cpdr.org

    2006-04-01

    In vitro human prostate cell culture models are critical for clarifying the mechanism of prostate cancer progression and for testing preventive and therapeutic agents. Cell lines ideal for the study of human primary prostate tumors would be those derived from spontaneously immortalized tumor cells; unfortunately, explanted primary prostate cells survive only short-term in culture, and rarely immortalize spontaneously. Therefore, we recently have generated five immortal human prostate epithelial cell cultures derived from both the benign and malignant tissues of prostate cancer patients with telomerase, a gene that prevents cellular senescence. Examination of these cell lines for their morphologies and proliferative capacities, their abilities to grow in low serum, to respond to androgen stimulation, to grow above the agar layer, to form tumors in SCID mice, suggests that they may serve as valid, useful tools for the elucidation of early events in prostate tumorigenesis. Furthermore, the chromosome alterations observed in these immortalized cell lines expressing aspects of the malignant phenotypes imply that these cell lines accurately recapitulate the genetic composition of primary tumors. These novel in vitro models may offer unique models for the study of prostate carcinogenesis and also provide the means for testing both chemopreventive and chemotherapeutic agents.

  11. Racial differences in adipose tissue distribution and risk of aggressive prostate cancer among men undergoing radiotherapy.

    PubMed

    Allott, Emma H; Howard, Lauren E; Song, Hai-Jun; Sourbeer, Katharine N; Koontz, Bridget F; Salama, Joseph K; Freedland, Stephen J

    2014-11-01

    Although elevated body mass index (BMI) has been associated with increased risk of aggressive prostate cancer, the importance of adipose tissue distribution is not well understood. We examined associations between overall and visceral obesity and aggressive prostate cancer risk. Moreover, given racial differences in adipose tissue distribution, we examined whether race modified these associations. We conducted a cross-sectional analysis of 308 radiotherapy-treated patients with prostate cancer within the Durham VA from 2005 to 2011. Multivariable logistic regression examined the association between BMI categories and tertiles of waist circumference (WC), visceral fat area (VFA), and periprostatic adipose tissue area (PPAT) with high-grade prostate cancer risk (Gleason score ≥7 vs. ≤6). Models stratified by race examined whether these associations differed between black and nonblack men. Both elevated BMI (Ptrend = 0.054) and WC (Ptrend = 0.040) were associated with increased high-grade prostate cancer risk, with similar results between races, although the association with BMI was not statistically significant. In contrast, elevated VFA was associated with increased aggressive prostate cancer risk in black men (Ptrend = 0.002) but not nonblack men (Ptrend = 0.831), with a significant interaction between race and VFA (Pinteraction = 0.035). Though similar patterns were observed for PPAT, none was statistically significant. Among men undergoing radiotherapy for prostate cancer, visceral obesity is associated with increased aggressive prostate cancer risk, particularly among black men. If confirmed in future studies, these results suggest that adipose tissue distribution differences may contribute to prostate cancer racial disparity. These findings highlight the need to elucidate mechanisms contributing to racial differences in the association between visceral obesity and aggressive prostate cancer. ©2014 American Association for Cancer Research.

  12. Second harmonic microscopic imaging and spectroscopic characterization in prostate pathological tissue.

    PubMed

    Huang, Yanyue; Zhuang, Zhengfei

    2014-01-01

    Second harmonic microscopic imaging and spectroscopy technology has become a powerful tool for biomedical studies, especially in cancer research. In this paper, second harmonic generation in benign prostatic hyperplasia (BPH) and prostate cancer (PC) tissues in mouse model (C57BL6) have been reported. Excitated samples with different wavelength near-infrared laser from 780 to 850 nm we found that second harmonic signals from BPH nuclei stronger than that from PC, and a wavelength sensitivity was also observed in this experiment. Providing useful help for prostate malignancy diagnosis and identifying tissue components on clinic. © 2013 Wiley Periodicals, Inc.

  13. Material characterization of ex vivo prostate tissue via spherical indentation in the clinic.

    PubMed

    Carson, William C; Gerling, Gregory J; Krupski, Tracey L; Kowalik, Casey G; Harper, Jeffrey C; Moskaluk, Christopher A

    2011-04-01

    The mechanical characterization of prostate tissue has not received much attention and is often disconnected from the clinic, where samples are readily attained. We developed a spherical indenter for the clinic to generate force-displacement data from ex vivo prostate tissue. Indentation velocity, depth, and sphere diameter, and four means of estimating elastic modulus (EM) were validated. EM was then estimated for 26 prostate specimens obtained via prostatectomy and 6 samples obtained from autopsy. Prostatectomy prostates were evaluated clinically upon digital rectal exam and pathologically post-extirpation. Whole-mount measurements yielded median EM of 43.2 kPa (SD=59.8 kPa). Once sliced into cross-sections, median EM for stage T2 and T3 glands were 30.9 and 71.0 kPa, respectively, but not significantly different. Furthermore, we compared within-organ EM difference for prostates with (median=46.5 kPa, SD=22.2 kPa) and without (median=31.0 kPa, SD=63.1 kPa) palpable abnormalities. This work finds that diseased prostate tissue is stiffer than normal tissue, stiffness increases with disease severity, and large variability exists between samples, even though disease differences within a prostate are detectable. A further study of late-stage cancers would help to strengthen the findings presented in this work. Copyright © 2010 IPEM. Published by Elsevier Ltd. All rights reserved.

  14. Xenotransplantation Models to Study the Effects of Toxicants on Human Fetal Tissues1

    PubMed Central

    Spade, Daniel J.; McDonnell, Elizabeth V.; Heger, Nicholas E.; Sanders, Jennifer A.; Saffarini, Camelia M.; Gruppuso, Philip A.; De Paepe, Monique E.; Boekelheide, Kim

    2015-01-01

    Many diseases that manifest throughout the lifetime are influenced by factors affecting fetal development. Fetal exposure to xenobiotics, in particular, may influence the development of adult diseases. Established animal models provide systems for characterizing both developmental biology and developmental toxicology. However, animal model systems do not allow researchers to assess the mechanistic effects of toxicants on developing human tissue. Human fetal tissue xenotransplantation models have recently been implemented to provide human-relevant mechanistic data on the many tissue-level functions that may be affected by fetal exposure to toxicants. This review describes the development of human fetal tissue xenotransplant models for testis, prostate, lung, liver, and adipose tissue, aimed at studying the effects of xenobiotics on tissue development, including implications for testicular dysgenesis, prostate disease, lung disease, and metabolic syndrome. The mechanistic data obtained from these models can complement data from epidemiology, traditional animal models, and in vitro studies to quantify the risks of toxicant exposures during human development. PMID:25477288

  15. P21-Activated Kinase Inhibitors FRAX486 and IPA3: Inhibition of Prostate Stromal Cell Growth and Effects on Smooth Muscle Contraction in the Human Prostate

    PubMed Central

    Wang, Yiming; Gratzke, Christian; Tamalunas, Alexander; Wiemer, Nicolas; Ciotkowska, Anna; Rutz, Beata; Waidelich, Raphaela; Strittmatter, Frank; Liu, Chunxiao; Stief, Christian G.; Hennenberg, Martin

    2016-01-01

    Prostate smooth muscle tone and hyperplastic growth are involved in the pathophysiology and treatment of male lower urinary tract symptoms (LUTS). Available drugs are characterized by limited efficacy. Patients’ adherence is particularly low to combination therapies of 5α-reductase inhibitors and α1-adrenoceptor antagonists, which are supposed to target contraction and growth simultaneously. Consequently, molecular etiology of benign prostatic hyperplasia (BPH) and new compounds interfering with smooth muscle contraction or growth in the prostate are of high interest. Here, we studied effects of p21-activated kinase (PAK) inhibitors (FRAX486, IPA3) in hyperplastic human prostate tissues, and in stromal cells (WPMY-1). In hyperplastic prostate tissues, PAK1, -2, -4, and -6 may be constitutively expressed in catecholaminergic neurons, while PAK1 was detected in smooth muscle and WPMY-1 cells. Neurogenic contractions of prostate strips by electric field stimulation were significantly inhibited by high concentrations of FRAX486 (30 μM) or IPA3 (300 μM), while noradrenaline- and phenylephrine-induced contractions were not affected. FRAX486 (30 μM) inhibited endothelin-1- and -2-induced contractions. In WPMY-1 cells, FRAX486 or IPA3 (24 h) induced concentration-dependent (1–10 μM) degeneration of actin filaments. This was paralleled by attenuation of proliferation rate, being observed from 1 to 10 μM FRAX486 or IPA3. Cytotoxicity of FRAX486 and IPA3 in WPMY-1 cells was time- and concentration-dependent. Stimulation of WPMY-1 cells with endothelin-1 or dihydrotestosterone, but not noradrenaline induced PAK phosphorylation, indicating PAK activation by endothelin-1. Thus, PAK inhibitors may inhibit neurogenic and endothelin-induced smooth muscle contractions in the hyperplastic human prostate, and growth of stromal cells. Targeting prostate smooth muscle contraction and stromal growth at once by a single compound is principally possible, at least under

  16. Characterization of human tissue carnosinase.

    PubMed Central

    Lenney, J F; Peppers, S C; Kucera-Orallo, C M; George, R P

    1985-01-01

    Human tissue carnosinase (EC 3.4.13.3) had optimum activity at pH9.5 and was a cysteine peptidase, being activated by dithiothreitol and inhibited by p-hydroxymercuribenzoate. By optimizing assay conditions, the activity per g of tissue was increased 10-fold compared with values in the literature. The enzyme was present in every human tissue assayed and was entirely different from serum carnosinase. Highly purified tissue carnosinase had a broader specificity than hog kidney carnosinase. Although tissue carnosinase was very strongly inhibited by bestatin, it did not hydrolyse tripeptides, and thus appears to be a dipeptidase rather than an aminopeptidase. It had a relative molecular mass of 90 000, an isoelectric point of 5.6, and a Km value of 10 mM-carnosine. Two forms of kidney and brain carnosinase were separated by high-resolution anion-exchange chromatography, although only one form was detected by various electrophoretic methods. Homocarnosinase and Mn2+-independent carnosinase were not detected in human tissues, although these enzymes are present in rat and hog kidney. PMID:4026801

  17. [Markers of prostate cancer stem cells: research advances].

    PubMed

    Wang, Shun-Qi; Huang, Sheng-Song

    2013-12-01

    Prostate cancer is one of the most seriously malignant diseases threatening men's health, and the mechanisms of its initiation and progression are not yet completely understood. Recent years have witnessed distinct advances in researches on prostate cancer stem cells in many aspects using different sources of materials, such as human prostate cancer tissues, human prostate cancer cell lines, and mouse models of prostate cancer. Prostate cancer stem cell study offers a new insight into the mechanisms of the initiation and progression of prostate cancer and contributes positively to its treatment. This article presents an overview on the prostate cancer stem cell markers utilized in the isolation and identification of prostate cancer stem cells.

  18. Expression and initial promoter characterization of PCAN1 in retinal tissue and prostate cell lines.

    PubMed

    Cross, D; Reding, D J; Salzman, S A; Zhang, K Q; Catalona, W J; Burke, J; Burmester, J K

    2004-01-01

    Prostate cancer is the most frequently diagnosed neoplasia in men and one of the leading causes of cancer-related deaths in men over 60. In an effort to understand the molecular events leading to prostate cancer, we have identified PCAN1 (prostate cancer gene 1) (also known as GDEP), a gene that is highly expressed in prostate epithelial tissue and frequently mutated in prostate tumors. Here we demonstrate its expression in neural retina, and retinoblastoma cell culture but not retinal pigment epithelial cell culture. We further characterize PCAN1 expression in the prostate cell lines RWPE1, RWPE2, and LnCAP FGC. We demonstrate an increase in expression when the cells are grown in the presence of Matrigel, an artificial extracellular basement membrane. Expression was time dependent, with expression observed on d 6 and little or no expression on d 12. Testosterone was not found to increase PCAN1 expression in this culture system. In addition, normal prostate epithelial cells co-cultured with normal prostate stromal cells did not exhibit PCAN1 expression at any time. To definitively locate the transcription initiation sites, we performed restriction-ligase-mediated 5' RACE, to selectively amplify only mRNA with a 5' cap. An initial characterization of the sequence upstream of the initiation sites determined six possible binding sites for the prostate specific regulatory protein NKX3.1 and four potential binding sites for the PPAR/RXR heterodimer that is involved in the control of cell differentiation and apoptosis.

  19. FGF signalling in prostate development, tissue homoeostasis and tumorigenesis.

    PubMed

    Lin, Yongshun; Wang, Fen

    2010-04-09

    The FGFs (fibroblast growth factors) regulate a broad spectrum of biological activities by activating transmembrane FGFR (FGF receptor) tyrosine kinases and their coupled intracellular signalling pathways. In the prostate, the mesenchymal-epithelial interactions mediated by androgen signalling and paracrine factors are essential for gland organogenesis, homoeostasis and tumorigenesis. FGFs mediate these mesenchymal-epithelial interactions in the prostate by paracrinal crosstalk through a diverse set of ligands and receptors. Gain- and loss-of-function studies in mouse models have demonstrated the requirement for the FGF signalling axis in prostate development and homoeostasis. The aberrant induction of this axis in either compartment of the prostate results in developmental disorders, disrupts the homoeostatic balance and leads to prostate carcinogenesis. FGFs are also implicated in mediating androgen signalling in the prostate between mesenchymal and epithelial compartments. Therefore studying FGF signalling in the prostate will help us to better understand the underlying molecular mechanisms by which the gland develops, maintains homoeostasis and undergoes carcinogenesis; as well as yield clues on how androgens mediate these processes and how advanced-tumour prostate cells escape strict androgen regulations.

  20. Overexpression and knock-down studies highlight that a disintegrin and metalloproteinase 28 controls proliferation and migration in human prostate cancer

    PubMed Central

    Rudnicka, Caroline; Mochizuki, Satsuki; Okada, Yasunori; McLaughlin, Claire; Leedman, Peter J.; Stuart, Lisa; Epis, Michael; Hoyne, Gerard; Boulos, Sherif; Johnson, Liam; Schlaich, Markus; Matthews, Vance

    2016-01-01

    Abstract Prostate cancer is one of the most prevalent cancers in men. It is critical to identify and characterize oncogenes that drive the pathogenesis of human prostate cancer. The current study builds upon previous research showing that a disintegrin and metallproteinase (ADAM)28 is involved in the pathogenesis of numerous cancers. Our novel study used overexpression, pharmacological, and molecular approaches to investigate the biological function of ADAM28 in human prostate cancer cells, with a focus on cell proliferation and migration. The results of this study provide important insights into the role of metalloproteinases in human prostate cancer. The expression of ADAM28 protein levels was assessed within human prostate tumors and normal adjacent tissue by immunohistochemistry. Immunocytochemistry and western blotting were used to assess ADAM28 protein expression in human prostate cancer cell lines. Functional assays were conducted to assess proliferation and migration in human prostate cancer cells in which ADAM28 protein expression or activity had been altered by overexpression, pharmacological inhibition, or by siRNA gene knockdown. The membrane bound ADAM28 was increased in human tumor biopsies and prostate cancer cell lines. Pharmacological inhibition of ADAM28 activity and/or knockdown of ADAM28 significantly reduced proliferation and migration of human prostate cancer cells, while overexpression of ADAM28 significantly increased proliferation and migration. ADAM28 is overexpressed in primary human prostate tumor biopsies, and it promotes human prostate cancer cell proliferation and migration. This study supports the notion that inhibition of ADAM28 may be a potential novel therapeutic strategy for human prostate cancer. PMID:27749584

  1. Overexpression and knock-down studies highlight that a disintegrin and metalloproteinase 28 controls proliferation and migration in human prostate cancer.

    PubMed

    Rudnicka, Caroline; Mochizuki, Satsuki; Okada, Yasunori; McLaughlin, Claire; Leedman, Peter J; Stuart, Lisa; Epis, Michael; Hoyne, Gerard; Boulos, Sherif; Johnson, Liam; Schlaich, Markus; Matthews, Vance

    2016-10-01

    Prostate cancer is one of the most prevalent cancers in men. It is critical to identify and characterize oncogenes that drive the pathogenesis of human prostate cancer. The current study builds upon previous research showing that a disintegrin and metallproteinase (ADAM)28 is involved in the pathogenesis of numerous cancers. Our novel study used overexpression, pharmacological, and molecular approaches to investigate the biological function of ADAM28 in human prostate cancer cells, with a focus on cell proliferation and migration. The results of this study provide important insights into the role of metalloproteinases in human prostate cancer.The expression of ADAM28 protein levels was assessed within human prostate tumors and normal adjacent tissue by immunohistochemistry. Immunocytochemistry and western blotting were used to assess ADAM28 protein expression in human prostate cancer cell lines. Functional assays were conducted to assess proliferation and migration in human prostate cancer cells in which ADAM28 protein expression or activity had been altered by overexpression, pharmacological inhibition, or by siRNA gene knockdown.The membrane bound ADAM28 was increased in human tumor biopsies and prostate cancer cell lines. Pharmacological inhibition of ADAM28 activity and/or knockdown of ADAM28 significantly reduced proliferation and migration of human prostate cancer cells, while overexpression of ADAM28 significantly increased proliferation and migration.ADAM28 is overexpressed in primary human prostate tumor biopsies, and it promotes human prostate cancer cell proliferation and migration. This study supports the notion that inhibition of ADAM28 may be a potential novel therapeutic strategy for human prostate cancer.

  2. Pre-clinical Orthotopic Murine Model of Human Prostate Cancer.

    PubMed

    Shahryari, Varahram; Nip, Hannah; Saini, Sharanjot; Dar, Altaf A; Yamamura, Soichiro; Mitsui, Yozo; Colden, Melissa; Bucay, Nathan; Tabatabai, Laura Z; Greene, Kirsten; Deng, Guoren; Tanaka, Yuichiro; Dahiya, Rajvir; Majid, Shahana

    2016-08-29

    To study the multifaceted biology of prostate cancer, pre-clinical in vivo models offer a range of options to uncover critical biological information about this disease. The human orthotopic prostate cancer xenograft mouse model provides a useful alternative approach for understanding the specific interactions between genetically and molecularly altered tumor cells, their organ microenvironment, and for evaluation of efficacy of therapeutic regimens. This is a well characterized model designed to study the molecular events of primary tumor development and it recapitulates the early events in the metastatic cascade prior to embolism and entry of tumor cells into the circulation. Thus it allows elucidation of molecular mechanisms underlying the initial phase of metastatic disease. In addition, this model can annotate drug targets of clinical relevance and is a valuable tool to study prostate cancer progression. In this manuscript we describe a detailed procedure to establish a human orthotopic prostate cancer xenograft mouse model.

  3. Differential expression of neuropilin-1 in malignant and benign prostatic stromal tissue.

    PubMed

    Vanveldhuizen, Peter J; Zulfiqar, Muhammad; Banerjee, Snigdha; Cherian, Rachel; Saxena, Neela K; Rabe, Amy; Thrasher, J Brantley; Banerjee, Sushanta K

    2003-01-01

    Neuropilin-1 (NRP-1), a co-receptor for VEGF165, is overexpressed in various prostate cancer cell lines and in advanced prostate tumors. However, distribution of the NRP-1 in prostate tumors has not yet been evaluated. Using immunohistochemical analysis, we evaluated 21 archival prostate tumors and 5 benign glands for the expression of NRP-1. In addition, we utilized a quantitative RT-PCR method to examine mRNA expression in 9 additional prostate tumors obtained from radical prostatectomy specimens and compared this expression to the adjacent normal tissue. The RT-PCR analyses demonstrated overexpression of NRP-1 mRNA in malignant tissue samples by 10.0-fold as compared to adjacent normal tissue. By immunohistochemistry, NRP-1 protein was undetected or minimally detected in the epithelial tumor cells. However, NRP-1 immuno-reaction was detected in the surrounding tumor stroma. Variable immuno-reaction for NRP-1 was also seen in the adjacent normal tumor stroma and the stroma of the benign prostate samples. These observations suggest that neuropilin-1 is expressed in the prostatic stromal cells, not epithelial tumor cells, and this expression is significantly increased in the malignant phenotype.

  4. Hydrogen sulfide mediates the anti-survival effect of sulforaphane on human prostate cancer cells

    SciTech Connect

    Pei, Yanxi; Wu, Bo; Cao, Qiuhui; Wu, Lingyun; Yang, Guangdong

    2011-12-15

    Hydrogen sulfide (H{sub 2}S) is a novel gasotransmitter that regulates cell proliferation and other cellular functions. Sulforaphane (SFN) is a sulfur-containing compound that exhibits anticancer properties, and young sprouts of broccoli are particularly rich in SFN. There is consistent epidemiological evidence that the consumption of sulfur-containing vegetables, such as garlic and cruciferous vegetables, may help reduce the occurrence of prostate cancer. Here we found that a large amount of H{sub 2}S is released when SFN is added into cell culture medium or mixed with mouse liver homogenates, respectively. Both SFN and NaHS (a H{sub 2}S donor) decreased the viability of PC-3 cells (a human prostate cancer cell line) in a dose-dependent manner, and supplement of methemoglobin or oxidized glutathione (two H{sub 2}S scavengers) reversed SFN-reduced cell viability. We further found both cystathionine gamma-lyase (CSE) and cystathionine beta-synthase are expressed in PC-3 cells and mouse prostate tissues. H{sub 2}S production in prostate tissues from CSE knockout mice was only 20% of that from wild-type mice, suggesting CSE is a major H{sub 2}S-producing enzyme in prostate. CSE overexpression enhanced H{sub 2}S production and inhibited cell viability in PC-3 cells. In addition, both SFN and NaHS activated p38 mitogen-activated protein kinases (MAPK) and c-Jun N-terminal kinase (JNK). Pre-treatment of PC-3 cells with methemoglobin decreased SFN-stimulated MAPK activities. Suppression of both p38 MAPK and JNK reversed H{sub 2}S- or SFN-reduced viability of PC-3 cells. Our results demonstrated that H{sub 2}S mediates the inhibitory effect of SFN on the proliferation of PC-3 cells, which suggests that H{sub 2}S-releasing diet or drug might be beneficial in the treatment of prostate cancer. Highlights: Black-Right-Pointing-Pointer A large amount of H{sub 2}S is released from sulforaphane. Black-Right-Pointing-Pointer H{sub 2}S mediates the anti-survival effect of

  5. Lysophosphatidic Acid Regulation and Roles in Human Prostate Cancer

    DTIC Science & Technology

    2006-08-01

    DAMD17-02-1-0060 TITLE: Lysophosphatidic Acid Regulation and Roles in Human Prostate Cancer PRINCIPAL INVESTIGATOR: Sarah Spiegel...Final 3. DATES COVERED (From - To) 2 Jan 2002 – 31 Jul 2006 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Lysophosphatidic Acid Regulation and Roles ...important role in the pathophysiology of prostate cancer. Therefore, targeting this kinase, offers additional therapeutic benefits in treatment of

  6. Prediction of Aggressive Human Prostate Cancer by Cathepsin B

    DTIC Science & Technology

    2008-03-01

    for CB was added to the wells. Following several washes to remove unbound antibody-enzyme reagent, a substrate solution HRP (horse- radish ...prostate cancer. Clin Cancer Res 6: 3430-3433, 2000. 8 Guo Y, Sigman DB, Borkowski A and Kyprianou N: Racial differences in prostate cancer growth ...cystatins in tumor growth and progression. Biol Chem Hoppe Seyler 1990;371 Suppl:193-198. 39. Yan S, Sloane BF. Molecular regulation of human cathepsin B

  7. Detection of prostate stem cell antigen expression in human prostate cancer using quantum-dot-based technology.

    PubMed

    Ruan, Yuan; Yu, Weimin; Cheng, Fan; Zhang, Xiaobin; Larré, Stéphane

    2012-01-01

    Quantum dots (QDs) are a new class of fluorescent labeling for biological and biomedical applications. In this study, we detected prostate stem cell antigen (PSCA) expression correlated with tumor grade and stage in human prostate cancer by QDs-based immunolabeling and conventional immunohistochemistry (IHC), and evaluated the sensitivity and stability of QDs-based immunolabeling in comparison with IHC. Our data revealed that increasing levels of PSCA expression accompanied advanced tumor grade (QDs labeling, r = 0.732, p < 0.001; IHC, r = 0.683, p < 0.001) and stage (QDs labeling, r = 0.514, p = 0.001; IHC, r = 0.432, p = 0.005), and the similar tendency was detected by the two methods. In addition, by comparison between the two methods, QDs labeling was consistent with IHC in detecting the expression of PSCA in human prostate tissue correlated with different pathological types (K = 0.845, p < 0.001). During the observation time, QDs exhibited superior stability. The intensity of QDs fluorescence remained stable for two weeks (p = 0.083) after conjugation to the PSCA protein, and nearly 93% of positive expression with their fluorescence still could be seen after four weeks.

  8. A Prospective Study of Chronic Inflammation in Benign Prostate Tissue and Risk of Prostate Cancer: Linked PCPT and SELECT Cohorts.

    PubMed

    Platz, Elizabeth A; Kulac, Ibrahim; Barber, John R; Drake, Charles G; Joshu, Corinne E; Nelson, William G; Lucia, M Scott; Klein, Eric A; Lippman, Scott M; Parnes, Howard L; Thompson, Ian M; Goodman, Phyllis J; Tangen, Catherine M; De Marzo, Angelo M

    2017-10-01

    Background: We leveraged two trials to test the hypothesis of an inflammation-prostate cancer link prospectively in men without indication for biopsy.Methods: Prostate Cancer Prevention Trial (PCPT) participants who had an end-of-study biopsy performed per protocol that was negative for cancer and who subsequently enrolled in the Selenium and Vitamin E Cancer Prevention Trial (SELECT) were eligible. We selected all 100 cases and sampled 200 frequency-matched controls and used PCPT end-of-study biopsies as "baseline." Five men with PSA > 4 ng/mL at end-of-study biopsy were excluded. Tissue was located for 92 cases and 193 controls. We visually assessed inflammation in benign tissue. We estimated ORs and 95% confidence intervals (CI) using logistic regression adjusting for age and race.Results: Mean time between biopsy and diagnosis was 5.9 years. In men previously in the PCPT placebo arm, 78.1% of cases (N = 41) and 68.2% of controls (N = 85) had at least one baseline biopsy core (∼5 evaluated per man) with inflammation. The odds of prostate cancer (N = 41 cases) appeared to increase with increasing mean percentage of tissue area with inflammation, a trend that was statistically significant for Gleason sum <4+3 disease (N = 31 cases; vs. 0%, >0-<1.8% OR = 1.70, 1.8-<5.0% OR = 2.39, ≥5% OR = 3.31, Ptrend = 0.047). In men previously in the finasteride arm, prevalence of inflammation did not differ between cases (76.5%; N = 51) and controls (75.0%; N = 108).Conclusions: Benign tissue inflammation was positively associated with prostate cancer.Impact: This first prospective study of men without biopsy indication supports the hypothesis that inflammation influences prostate cancer development. Cancer Epidemiol Biomarkers Prev; 26(10); 1549-57. ©2017 AACR. ©2017 American Association for Cancer Research.

  9. Differentially Expressed Genes and Signature Pathways of Human Prostate Cancer

    PubMed Central

    Myers, Jennifer S.; von Lersner, Ariana K.; Robbins, Charles J.; Sang, Qing-Xiang Amy

    2015-01-01

    Genomic technologies including microarrays and next-generation sequencing have enabled the generation of molecular signatures of prostate cancer. Lists of differentially expressed genes between malignant and non-malignant states are thought to be fertile sources of putative prostate cancer biomarkers. However such lists of differentially expressed genes can be highly variable for multiple reasons. As such, looking at differential expression in the context of gene sets and pathways has been more robust. Using next-generation genome sequencing data from The Cancer Genome Atlas, differential gene expression between age- and stage- matched human prostate tumors and non-malignant samples was assessed and used to craft a pathway signature of prostate cancer. Up- and down-regulated genes were assigned to pathways composed of curated groups of related genes from multiple databases. The significance of these pathways was then evaluated according to the number of differentially expressed genes found in the pathway and their position within the pathway using Gene Set Enrichment Analysis and Signaling Pathway Impact Analysis. The “transforming growth factor-beta signaling” and “Ran regulation of mitotic spindle formation” pathways were strongly associated with prostate cancer. Several other significant pathways confirm reported findings from microarray data that suggest actin cytoskeleton regulation, cell cycle, mitogen-activated protein kinase signaling, and calcium signaling are also altered in prostate cancer. Thus we have demonstrated feasibility of pathway analysis and identified an underexplored area (Ran) for investigation in prostate cancer pathogenesis. PMID:26683658

  10. Tissue mimicking materials for the detection of prostate cancer using shear wave elastography: a validation study.

    PubMed

    Cao, Rui; Huang, Zhihong; Varghese, Tomy; Nabi, Ghulam

    2013-02-01

    Quantification of stiffness changes may provide important diagnostic information and aid in the early detection of cancers. Shear wave elastography is an imaging technique that assesses tissue stiffness using acoustic radiation force as an alternate to manual palpation reported previously with quasistatic elastography. In this study, the elastic properties of tissue mimicking materials, including agar, polyacrylamide (PAA), and silicone, are evaluated with an objective to determine material characteristics which resemble normal and cancerous prostate tissue. Acoustic properties and stiffness of tissue mimicking phantoms were measured using compressional mechanical testing and shear wave elastography using supersonic shear imaging. The latter is based on the principles of shear waves generated using acoustic radiation force. The evaluation included tissue mimicking materials (TMMs) within the prostate at different positions and sizes that could mimic cancerous and normal prostate tissue. Patient data on normal and prostate cancer tissues quantified using biopsy histopathology were used to validate the findings. Pathologist reports on histopathology were blinded to mechanical testing and elastographic findings. Young's modulus values of 86.2 ± 4.5 and 271.5 ± 25.7 kPa were obtained for PAA mixed with 2% Al(2)O(3) particles and silicone, respectively. Young's modulus of TMMs from mechanical compression testing showed a clear trend of increasing stiffness with an increasing percentage of agar. The silicone material had higher stiffness values when compared with PAA with Al(2)O(3). The mean Young's modulus value in cancerous tissue was 90.5 ± 4.5 kPa as compared to 93.8 ± 4.4 and 86.2 ± 4.5 kPa obtained with PAA with 2% Al(2)O(3) phantom at a depth of 52.4 and 36.6 mm, respectively. PAA mixed with Al(2)O(3) provides the most suitable tissue mimicking material for prostate cancer tumor material, while agar could form the surrounding background to simulate normal

  11. Coagulation of human prostate volumes with MRI-controlled transurethral ultrasound therapy: Results in gel phantoms

    PubMed Central

    N’Djin, William Apoutou; Burtnyk, Mathieu; Kobelevskiy, Ilya; Hadjis, Stefan; Bronskill, Michael; Chopra, Rajiv

    2012-01-01

    Purpose: The feasibility and safety of magnetic resonance imaging (MRI)-controlled transurethral ultrasound therapy were demonstrated recently in a preliminary human study in which a small subvolume of prostate tissue was treated prior to radical prostatectomy. Translation of this technology to full clinical use, however, requires the capability to generate thermal coagulation in a volume up to that of the prostate gland itself. The aim of this study was to investigate the parameters required to treat a full 3D human prostate accurately with a multi-element transurethral applicator and multiplanar MR temperature control. Methods: The approach was a combination of simulations (to select appropriate parameters) followed by experimental confirmation in tissue-mimicking phantoms. A ten-channel, MRI-compatible transurethral ultrasound therapy system was evaluated using six human prostate models (average volume: 36 cm3) obtained from the preliminary human feasibility study. Real-time multiplanar MR thermometry at 3 T was used to control the spatial heating pattern in up to nine planes simultaneously. Treatment strategies incorporated both single (4.6 or 8.1 MHz) and dual (4.6 and 14.4 MHz) frequencies, as well as maximum acoustic surface powers of 10 or 20 W cm−2. Results: Treatments at 4.6 MHz were capable of coagulating a volume equivalent to 97% of the prostate. Increasing power from 10 to 20 W cm−2 reduced treatment times by approximately 50% with full treatments taking 26 ± 3 min at a coagulation rate of 1.8 ± 0.4 cm3 min−1. A dual-frequency 4.6/14.4 MHz treatment strategy was shown to be the most effective configuration for achieving full human prostate treatment while maintaining good treatment accuracy for small treatment radii. The dual-frequency approach reduced overtreatment close to the prostate base and apex, confirming the simulations. Conclusions: This study reinforces the capability of MRI-controlled transurethral ultrasound therapy to treat

  12. Coagulation of human prostate volumes with MRI-controlled transurethral ultrasound therapy: Results in gel phantoms.

    PubMed

    N'Djin, William Apoutou; Burtnyk, Mathieu; Kobelevskiy, Ilya; Hadjis, Stefan; Bronskill, Michael; Chopra, Rajiv

    2012-07-01

    The feasibility and safety of magnetic resonance imaging (MRI)-controlled transurethral ultrasound therapy were demonstrated recently in a preliminary human study in which a small subvolume of prostate tissue was treated prior to radical prostatectomy. Translation of this technology to full clinical use, however, requires the capability to generate thermal coagulation in a volume up to that of the prostate gland itself. The aim of this study was to investigate the parameters required to treat a full 3D human prostate accurately with a multi-element transurethral applicator and multiplanar MR temperature control. The approach was a combination of simulations (to select appropriate parameters) followed by experimental confirmation in tissue-mimicking phantoms. A ten-channel, MRI-compatible transurethral ultrasound therapy system was evaluated using six human prostate models (average volume: 36 cm(3) ) obtained from the preliminary human feasibility study. Real-time multiplanar MR thermometry at 3 T was used to control the spatial heating pattern in up to nine planes simultaneously. Treatment strategies incorporated both single (4.6 or 8.1 MHz) and dual (4.6 and 14.4 MHz) frequencies, as well as maximum acoustic surface powers of 10 or 20 W cm(-2) . Treatments at 4.6 MHz were capable of coagulating a volume equivalent to 97% of the prostate. Increasing power from 10 to 20 W cm(-2) reduced treatment times by approximately 50% with full treatments taking 26 ± 3 min at a coagulation rate of 1.8 ± 0.4 cm(3)  min(-1) . A dual-frequency 4.6/14.4 MHz treatment strategy was shown to be the most effective configuration for achieving full human prostate treatment while maintaining good treatment accuracy for small treatment radii. The dual-frequency approach reduced overtreatment close to the prostate base and apex, confirming the simulations. This study reinforces the capability of MRI-controlled transurethral ultrasound therapy to treat full prostate volumes in a

  13. Coagulation of human prostate volumes with MRI-controlled transurethral ultrasound therapy: results in gel phantoms.

    PubMed

    N'djin, William Apoutou; Burtnyk, Mathieu; Kobelevskiy, Ilya; Hadjis, Stefan; Bronskill, Michael; Chopra, Rajiv

    2012-07-01

    The feasibility and safety of magnetic resonance imaging (MRI)-controlled transurethral ultrasound therapy were demonstrated recently in a preliminary human study in which a small subvolume of prostate tissue was treated prior to radical prostatectomy. Translation of this technology to full clinical use, however, requires the capability to generate thermal coagulation in a volume up to that of the prostate gland itself. The aim of this study was to investigate the parameters required to treat a full 3D human prostate accurately with a multi-element transurethral applicator and multiplanar MR temperature control. The approach was a combination of simulations (to select appropriate parameters) followed by experimental confirmation in tissue-mimicking phantoms. A ten-channel, MRI-compatible transurethral ultrasound therapy system was evaluated using six human prostate models (average volume: 36 cm(3)) obtained from the preliminary human feasibility study. Real-time multiplanar MR thermometry at 3 T was used to control the spatial heating pattern in up to nine planes simultaneously. Treatment strategies incorporated both single (4.6 or 8.1 MHz) and dual (4.6 and 14.4 MHz) frequencies, as well as maximum acoustic surface powers of 10 or 20 W cm(-2). Treatments at 4.6 MHz were capable of coagulating a volume equivalent to 97% of the prostate. Increasing power from 10 to 20 W cm(-2) reduced treatment times by approximately 50% with full treatments taking 26 ± 3 min at a coagulation rate of 1.8 ± 0.4 cm(3) min(-1). A dual-frequency 4.6∕14.4 MHz treatment strategy was shown to be the most effective configuration for achieving full human prostate treatment while maintaining good treatment accuracy for small treatment radii. The dual-frequency approach reduced overtreatment close to the prostate base and apex, confirming the simulations. This study reinforces the capability of MRI-controlled transurethral ultrasound therapy to treat full prostate volumes in a short

  14. Testosterone uptake by prostatic tissue from young and old rats.

    PubMed

    Ghanadian, R; Fotherby, K

    1975-01-01

    The uptake of [3H]-testosterone in vitro by the ventral lobe of the prostate of rats more than 11 months old was significantly less than that of rats 4-5 weeks old. There were significant decreases between young and old rats in the RNA and DNA content of the prostate but not in the activity of acid or alkaline phosphatases. Alkaline phosphatase activity was higher than that of acid phosphatase. Testosterone uptake by the prostate was higher in culture medium TC199 than in Krebs-Ringer buffer solution.

  15. Comparison of Prostatic Tissue Processed by Microwave and Conventional Technique Using Morphometry

    PubMed Central

    Jain, Promil; Kumar, Sanjay; Arora, B; Singh, Sneh; Chabbra, Sonia; Sen, Rajeev

    2015-01-01

    Background and Objectives: Rapid processing of histopathological specimens and decreased turnaround time is important to fulfill the needs of clinicians treating sick patients, so the present study was conducted to compare the time taken and quality of sections in processing of prostatic tissue by rapid microwave and conventional techniques using morphometry. Methods: Four to five mm thick paired prostate tissue pieces of fifty cases of prostatectomy specimens were taken. One tissue piece of the pair was processed routinely overnight by conventional tissue processing and the other by microwave processing. Time taken for processing by both conventional technique and microwave technique was noted and compared. Then, both were stained with conventional method of hematoxylin and eosin staining and examined for histological typing and grading. Morphometric study was done on slides of prostatic tissue processed by both conventional and microwave technique. Result: The prostatectomy specimens included both benign (86%) and malignant (14%) prostatic lesions in the age range of 46-85 years. The time taken for steps of dehydration, clearing and impregnation in microwave technique was significantly less as compared to histoprocessing done by conventional technique. Morphology, staining patterns of prostatic tissue processed within minutes by microwave technique, whether benign or malignant, were comparable to those sections which were processed in days using standard technique. Conclusion: Domestic microwave oven can be used for histoprocessing to accelerate the processing with preservation of morphology and is cheaper than commercially available microwave ovens and processing time was considerably reduced from days to minutes. PMID:26516319

  16. Comparison of Prostatic Tissue Processed by Microwave and Conventional Technique Using Morphometry.

    PubMed

    Jain, Promil; Kumar, Sanjay; Arora, B; Singh, Sneh; Chabbra, Sonia; Sen, Rajeev

    2015-01-01

    Rapid processing of histopathological specimens and decreased turnaround time is important to fulfill the needs of clinicians treating sick patients, so the present study was conducted to compare the time taken and quality of sections in processing of prostatic tissue by rapid microwave and conventional techniques using morphometry. Four to five mm thick paired prostate tissue pieces of fifty cases of prostatectomy specimens were taken. One tissue piece of the pair was processed routinely overnight by conventional tissue processing and the other by microwave processing. Time taken for processing by both conventional technique and microwave technique was noted and compared. Then, both were stained with conventional method of hematoxylin and eosin staining and examined for histological typing and grading. Morphometric study was done on slides of prostatic tissue processed by both conventional and microwave technique. The prostatectomy specimens included both benign (86%) and malignant (14%) prostatic lesions in the age range of 46-85 years. The time taken for steps of dehydration, clearing and impregnation in microwave technique was significantly less as compared to histoprocessing done by conventional technique. Morphology, staining patterns of prostatic tissue processed within minutes by microwave technique, whether benign or malignant, were comparable to those sections which were processed in days using standard technique. Domestic microwave oven can be used for histoprocessing to accelerate the processing with preservation of morphology and is cheaper than commercially available microwave ovens and processing time was considerably reduced from days to minutes.

  17. Tissue Engineered Human Skin Equivalents

    PubMed Central

    Zhang, Zheng; Michniak-Kohn, Bozena B.

    2012-01-01

    Human skin not only serves as an important barrier against the penetration of exogenous substances into the body, but also provides a potential avenue for the transport of functional active drugs/reagents/ingredients into the skin (topical delivery) and/or the body (transdermal delivery). In the past three decades, research and development in human skin equivalents have advanced in parallel with those in tissue engineering and regenerative medicine. The human skin equivalents are used commercially as clinical skin substitutes and as models for permeation and toxicity screening. Several academic laboratories have developed their own human skin equivalent models and applied these models for studying skin permeation, corrosivity and irritation, compound toxicity, biochemistry, metabolism and cellular pharmacology. Various aspects of the state of the art of human skin equivalents are reviewed and discussed. PMID:24300178

  18. Nonylphenol effects on human prostate non tumorigenic cells.

    PubMed

    Forte, Maurizio; Di Lorenzo, Mariana; Carrizzo, Albino; Valiante, Salvatore; Vecchione, Carmine; Laforgia, Vincenza; De Falco, Maria

    2016-05-16

    Nonylphenol (NP) is an industrial chemical with estrogenic activity both in vivo and in vitro; estrogens play a critical role in the development of prostate and may be the cause of some pathological states, including cancer. In this study we examined the effects of NP on human prostate non tumorigenic epithelial cells (PNT1A) investigating on cell proliferation, interaction with estrogen receptors (ERs) and gene expression of genes involved in prostate diseases. We found that NP affects cell proliferation at 10(-6)M, promoting a cytoplasm-nucleus translocation of ERα and not ERβ, like the natural estrogen 17β-estradiol (E2). Moreover, we showed that NP enhances gene expression of key regulators of cell cycle. Estrogen selective antagonist ICI182780 in part reverted the observed effects of NP. These results confirm the estrogenic activity of NP and suggest that other transduction pathways may be involved in NP action on prostate.

  19. Detecting mechanical abnormalities in prostate tissue using FE-based image registration.

    PubMed

    Courtis, Patrick; Samani, Abbas

    2007-01-01

    An image registration-based elastography algorithm is presented for assessing the stiffness of tissue regions inside the prostate for the purpose of detecting tumors. A 3D finite-element model of the prostate is built from ultrasound images and used to simulate the deformation of the prostate induced by a TRUS probe. To reconstruct the stiffness of tissues, their Young's moduli are varied using Powell's method so that the mutual information between a simulated and deformed image volume is maximized. The algorithm was validated using a gelatin prostate phantom embedded with a cylindrical inclusion that simulated a tumor. Results from the phantom study showed that the technique could detect the increased stiffness of the simulated tumor with a reasonable accuracy.

  20. Tissue engineering a human phalanx.

    PubMed

    Landis, W J; Chubinskaya, S; Tokui, T; Wada, Y; Isogai, N; Jacquet, R

    2016-03-21

    A principal purpose of tissue engineering is the augmentation, repair or replacement of diseased or injured human tissue. This study was undertaken to determine whether human biopsies as a cell source could be utilized for successful engineering of human phalanges consisting of both bone and cartilage. This paper reports the use of cadaveric human chondrocytes and periosteum as a model for the development of phalanx constructs. Two factors, osteogenic protein-1 [OP-1/bone morphogenetic protein-7 (BMP7)], alone or combined with insulin-like growth factor (IGF-1), were examined for their potential enhancement of chondrocytes and their secreted extracellular matrices. Design of the study included culture of chondrocytes and periosteum on biodegradable polyglycolic acid (PGA) and poly-l-lactic acid (PLLA)-poly-ε-caprolactone (PCL) scaffolds and subsequent implantation in athymic nu/nu (nude) mice for 5, 20, 40 and 60 weeks. Engineered constructs retrieved from mice were characterized with regard to genotype and phenotype as a function of developmental (implantation) time. Assessments included gross observation, X-ray radiography or microcomputed tomography, histology and gene expression. The resulting data showed that human cell-scaffold constructs could be successfully developed over 60 weeks, despite variability in donor age. Cartilage formation of the distal phalanx models enhanced with both OP-1 and IGF-1 yielded more cells and extracellular matrix (collagen and proteoglycans) than control chondrocytes without added factors. Summary data demonstrated that human distal phalanx models utilizing cadaveric chondrocytes and periosteum were successfully fabricated and OP-1 and OP-1/IGF-1 accelerated construct development and mineralization. The results suggest that similar engineering and transplantation of human autologous tissues in patients are clinically feasible. Copyright © 2016 John Wiley & Sons, Ltd.

  1. Advancing the Capabilities of an Authentic Ex Vivo Model of Primary Human Prostate Cancer

    DTIC Science & Technology

    2014-10-01

    which slices of human PCa are embedded under the renal capsules of immune-deficient mice (21, 22). The TSG model will benefit from extending the...performed sub- renal implantation of benign TSCs that have been cultured for 3 days, combining the in vitro TSC and in vivo TSG models . Future work...characterization of in vivo tumorgraft models for primary prostate cancer in which thin, precision-cut slices of tissue are implanted under the renal

  2. Human kallikrein 4 signal peptide induces cytotoxic T cell responses in healthy donors and prostate cancer patients.

    PubMed

    Wilkinson, Ray; Woods, Katherine; D'Rozario, Rachael; Prue, Rebecca; Vari, Frank; Hardy, Melinda Y; Dong, Ying; Clements, Judith A; Hart, Derek N J; Radford, Kristen J

    2012-02-01

    Immunotherapy is a promising new treatment for patients with advanced prostate and ovarian cancer, but its application is limited by the lack of suitable target antigens that are recognized by CD8+ cytotoxic T lymphocytes (CTL). Human kallikrein 4 (KLK4) is a member of the kallikrein family of serine proteases that is significantly overexpressed in malignant versus healthy prostate and ovarian tissue, making it an attractive target for immunotherapy. We identified a naturally processed, HLA-A*0201-restricted peptide epitope within the signal sequence region of KLK4 that induced CTL responses in vitro in most healthy donors and prostate cancer patients tested. These CTL lysed HLA-A*0201+ KLK4 + cell lines and KLK4 mRNA-transfected monocyte-derived dendritic cells. CTL specific for the HLA-A*0201-restricted KLK4 peptide were more readily expanded to a higher frequency in vitro compared to the known HLA-A*0201-restricted epitopes from prostate cancer antigens; prostate-specific antigen (PSA), prostate-specific membrane antigen (PSMA) and prostatic acid phosphatase (PAP). These data demonstrate that KLK4 is an immunogenic molecule capable of inducing CTL responses and identify it as an attractive target for prostate and ovarian cancer immunotherapy.

  3. An Embryonic Growth Pathway is Reactivated in Human Prostate Cancer

    DTIC Science & Technology

    2005-06-01

    assess growth of the four cell lines, a Gompertz prostatectomy (n = 2), and six prostate cancer (PC) speci- growth model was fitted to each line. Day... Gompertz model with men (N), in hyperplastic (benign) tissue from men without line-specific asymptote and growth rate was estimated via Gauss-New...histologically confirmed tumor with histologically con- The plots and Gompertz fits were generated in R version 1.6.25.1 (36). firmed benign tissue obtained from

  4. Light penetration in the human prostate: a whole prostate clinical study at 763 nm

    NASA Astrophysics Data System (ADS)

    Moore, Caroline M.; Mosse, C. Alexander; Allen, Clare; Payne, Heather; Emberton, Mark; Bown, Stephen G.

    2011-01-01

    Photodynamic therapy (PDT) is being investigated as a treatment for localized prostate cancer. Photodynamic therapy uses a photosensitizing drug which is activated by a specific wavelength of light, in the presence of oxygen. The activated drug reacts with tissue oxygen to produce reactive oxygen species which are responsible for localized tissue necrosis. One of the determinants of the PDT effect is the penetration of light in the prostate. This study assesses the penetration depth of 763 nm light throughout the prostate. Eight men undergoing multiple hollow needle insertion for high dose rate brachytherapy were recruited. 763 nm light, produced by a diode laser, was delivered to the prostate using cylindrically diffusing optical fibers within the plastic needles. Light was detected at different distances from the source, using an isotropic detector within nearby needles. Penetration depth was calculated using the Boltzmann approximation to the diffusion equation. Delivery detector fiber separation was measured on computed tomography. The mean penetration depth was 0.57 cm, but there was within patient variation of a mean factor of 4.3. Further work is ongoing to assess the effect of such variability in light penetration, on the PDT effect.

  5. Molecular profiling of indolent human prostate cancer: tackling technical challenges to achieve high-fidelity genome-wide data.

    PubMed

    Dunn, Thomas A; Fedor, Helen L; De Marzo, Angelo M; Luo, Jun

    2012-05-01

    The contemporary problem of prostate cancer overtreatment can be partially attributed to the diagnosis of potentially indolent prostate cancers that pose low risk to aged men, and lack of sufficiently accurate risk stratification methods to reliably seek out men with indolent diseases. Since progressive acquisition and accumulation of genomic alterations, both genetic and epigenetic, is a defining feature of all human cancers at different stages of disease progression, it is hypothesized that RNA and DNA alterations characteristic of indolent prostate tumors may be different from those previously characterized in the setting of clinically significant prostate cancer. Approaches capable of detecting such alterations on a genome-wide level are the most promising. Such analysis may uncover molecular events defining early initiating stages along the natural history of prostate cancer progression, and ultimately lead to rational development of risk stratification methods for identification of men who can safely forego treatment. However, defining and characterizing indolent prostate cancer in a clinically relevant context remains a challenge, particularly when genome-wide approaches are employed to profile formalin-fixed paraffin-embedded (FFPE) tissue specimens. Here, we provide the conceptual basis underlying the importance of understanding indolent prostate cancer from molecular profiling studies, identify the key hurdles in sample acquisition and variables that affect molecular data derived from FFPE tissues, and highlight recent progresses in efforts to address these technical challenges.

  6. Chronic inflammation in benign prostate tissue is associated with high-grade prostate cancer in the placebo arm of the Prostate Cancer Prevention Trial*

    PubMed Central

    Gurel, Bora; Lucia, M. Scott; Thompson, Ian M.; Goodman, Phyllis J.; Tangen, Catherine M.; Kristal, Alan R.; Parnes, Howard L.; Hoque, Ashraful; Lippman, Scott M.; Sutcliffe, Siobhan; Peskoe, Sarah B.; Drake, Charles G.; Nelson, William G.; De Marzo, Angelo M.; Platz, Elizabeth A.

    2014-01-01

    Background Chronic inflammation is hypothesized to influence prostate cancer development, although a definitive link has not been established. Methods Prostate cancer cases (N=191) detected on a for-cause (clinically indicated) or end-of-study (protocol directed) biopsy, and frequency-matched controls (N=209), defined as negative for cancer on an end-of-study biopsy, were sampled from the placebo arm of the Prostate Cancer Prevention Trial. Inflammation prevalence and extent in benign areas of biopsy cores were visually assessed using digital images of H&E stained sections. Logistic regression was used to estimate associations. Results 86.2% of cases and 78.2% of controls had at least one biopsy core (of 3 assessed) with inflammation in benign areas, most of which was chronic. Men who had at least one biopsy core with inflammation had 1.78 (95% CI 1.04–3.06) times the odds of prostate cancer compared with men who had zero cores with inflammation. The association was stronger for high-grade disease (Gleason sum 7–10, N=94; odds ratio [OR]=2.24, 95% CI 1.06–4.71). These patterns were present when restricting to cases and controls in whom intraprostatic inflammation was the least likely to have influenced biopsy recommendation because their PSA was low (<2 ng/mL at biopsy). Conclusion Inflammation, most of which was chronic, was common in benign prostate tissue, and was positively associated with prostate cancer, especially high-grade. The association did not appear to be due to detection bias. Impact This study supports an etiologic link between inflammation and prostate carcinogenesis, and suggests an avenue for prevention by mitigating intraprostatic inflammation. PMID:24748218

  7. Prostate cancer in native Japanese and Japanese-American men: effects of dietary differences on prostatic tissue.

    PubMed

    Marks, Leonard S; Kojima, Munekado; Demarzo, Angelo; Heber, David; Bostwick, David G; Qian, Junqi; Dorey, Frederick J; Veltri, Robert W; Mohler, James L; Partin, Alan W

    2004-10-01

    To investigate the relationship between diet and prostate cancer (CaP) among native Japanese (NJ) and second-generation or third-generation Japanese-American (J-A) men--focusing on the effects of animal fat and soy on prostatic tissues. The subjects were 50 Japanese men undergoing radical prostatectomy, 25 NJ living in Nagoya, Japan and 25 U.S.-born J-A men, living in Los Angeles, California. A priori, the NJ men were believed to be a low-fat, high-soy group and the J-A men, a high-fat, low-soy group. The studies included postoperative measurements of diet (Block questionnaire), body fat (bioimpedance), blood, urine, and prostatic biomarkers in malignant and adjacent normal tissue, using a tissue microarray made from the original paraffin blocks. The NJ and J-A men were similar in age (65 to 70 years old; P <0.05), prostate-specific antigen level (7.1 to 8.6 ng/mL), prostate volume (35 to 38 cm3), and Gleason score (5.6 to 6.6), but their body composition differed. J-A men had more body fat (24% versus 19%), higher serum triglyceride levels (245 versus 106 mg/dL), lower estradiol levels (27 versus 31 ng/mL), and much lower urinary soy-metabolite levels (1:3) than NJ men (P <0.02). In both NJ and J-A groups, expression of numerous tissue biomarkers separated normal from CaP tissue, including markers for apoptosis (Bcl-2, caspase-3), growth factor receptors (epidermal growth factor receptor), racemase, 5-lipoxygenase, kinase inhibition (p27), and cell proliferation (Ki-67; all P <0.02). Furthermore, within both normal and CaP tissues, caspase-3 and 5-lipoxygenase were expressed more in NJ than in J-A men (P <0.01). Nuclear morphometry showed that the chromatin in each of the four groups (normal versus CaP, NJ versus J-A) was different (area under the curve 85% to 94%, P <0.01), despite fundamental genetic homogeneity. NJ and J-A men, products of similar genetics but differing environments, were shown to have differences in body composition that could influence Ca

  8. Distribution of miRNA expression across human tissues

    PubMed Central

    Ludwig, Nicole; Leidinger, Petra; Becker, Kurt; Backes, Christina; Fehlmann, Tobias; Pallasch, Christian; Rheinheimer, Steffi; Meder, Benjamin; Stähler, Cord; Meese, Eckart; Keller, Andreas

    2016-01-01

    We present a human miRNA tissue atlas by determining the abundance of 1997 miRNAs in 61 tissue biopsies of different organs from two individuals collected post-mortem. One thousand three hundred sixty-four miRNAs were discovered in at least one tissue, 143 were present in each tissue. To define the distribution of miRNAs, we utilized a tissue specificity index (TSI). The majority of miRNAs (82.9%) fell in a middle TSI range i.e. were neither specific for single tissues (TSI > 0.85) nor housekeeping miRNAs (TSI < 0.5). Nonetheless, we observed many different miRNAs and miRNA families that were predominantly expressed in certain tissues. Clustering of miRNA abundances revealed that tissues like several areas of the brain clustered together. Considering -3p and -5p mature forms we observed miR-150 with different tissue specificity. Analysis of additional lung and prostate biopsies indicated that inter-organism variability was significantly lower than inter-organ variability. Tissue-specific differences between the miRNA patterns appeared not to be significantly altered by storage as shown for heart and lung tissue. MiRNAs TSI values of human tissues were significantly (P = 10−8) correlated with those of rats; miRNAs that were highly abundant in certain human tissues were likewise abundant in according rat tissues. We implemented a web-based repository enabling scientists to access and browse the data (https://ccb-web.cs.uni-saarland.de/tissueatlas). PMID:26921406

  9. Distribution of miRNA expression across human tissues.

    PubMed

    Ludwig, Nicole; Leidinger, Petra; Becker, Kurt; Backes, Christina; Fehlmann, Tobias; Pallasch, Christian; Rheinheimer, Steffi; Meder, Benjamin; Stähler, Cord; Meese, Eckart; Keller, Andreas

    2016-05-05

    We present a human miRNA tissue atlas by determining the abundance of 1997 miRNAs in 61 tissue biopsies of different organs from two individuals collected post-mortem. One thousand three hundred sixty-four miRNAs were discovered in at least one tissue, 143 were present in each tissue. To define the distribution of miRNAs, we utilized a tissue specificity index (TSI). The majority of miRNAs (82.9%) fell in a middle TSI range i.e. were neither specific for single tissues (TSI > 0.85) nor housekeeping miRNAs (TSI < 0.5). Nonetheless, we observed many different miRNAs and miRNA families that were predominantly expressed in certain tissues. Clustering of miRNA abundances revealed that tissues like several areas of the brain clustered together. Considering -3p and -5p mature forms we observed miR-150 with different tissue specificity. Analysis of additional lung and prostate biopsies indicated that inter-organism variability was significantly lower than inter-organ variability. Tissue-specific differences between the miRNA patterns appeared not to be significantly altered by storage as shown for heart and lung tissue. MiRNAs TSI values of human tissues were significantly (P = 10(-8)) correlated with those of rats; miRNAs that were highly abundant in certain human tissues were likewise abundant in according rat tissues. We implemented a web-based repository enabling scientists to access and browse the data (https://ccb-web.cs.uni-saarland.de/tissueatlas).

  10. Erythropoietin receptor expression in the human urogenital tract: immunolocalization in the prostate, neurovascular bundle and penis.

    PubMed

    Liu, Tongyun; Allaf, Mohamad E; Lagoda, Gwen; Burnett, Arthur L

    2007-11-01

    To investigate whether the erythropoietin (EPO) receptor is expressed in human periprostatic (including the neurovascular bundles) and penile tissues, and define its distribution in these tissues, as the administration of exogenous EPO in cavernous nerve injury promoted the recovery of erectile function in a rat model. Human prostate (six samples) and penile (two) tissue were collected and paraffin-embedded. Tissue was sectioned and processed for immunohistochemical studies using an antibody for the EPO receptor; immunolocalization was assessed using light microscopy. There was prominent staining for the EPO receptor in neuronal cell bodies of the periprostatic neurovascular bundles, and in the axons emanating from these ganglia. The glandular epithelium of the prostate also had weak staining. There was EPO receptor immunoreactivity in the penile specimens in the penile dorsal nerves, sinusoidal endothelium of the corpus cavernosum, and endothelial cells lining the dorsal veins and arteries. All slides processed with no primary antibody or blocking peptide showed no staining. EPO receptor expression was identified and localized in human penile tissues and in the periprostatic neurovascular bundles responsible for erectile function. This suggests a likely role for endogenous EPO within these tissues, and provides the rationale for its clinical use as a protective agent locally.

  11. Inter- and intra-observer variability in prostate definition with tissue harmonic and brightness mode imaging.

    PubMed

    Sandhu, Gurpreet Kaur; Dunscombe, Peter; Meyer, Tyler; Pavamani, Simon; Khan, Rao

    2012-01-01

    The objective of this study was to compare the relative utility of tissue harmonic (H) and brightness (B) transrectal ultrasound (TRUS) images of the prostate by studying interobserver and intraobserver variation in prostate delineation. Ten patients with early-stage disease were randomly selected. TRUS images of prostates were acquired using B and H modes. The prostates on all images were contoured by an experienced radiation oncologist (RO) and five equally trained observers. The observers were blinded to information regarding patient and imaging mode. The volumes of prostate glands and areas of midgland slices were calculated. Volumes contoured were compared among the observers and between observer group and RO. Contours on one patient were repeated five times by four observers to evaluate the intraobserver variability. A one-sample Student t-test showed the volumes outlined by five observers are in agreement (p > 0.05) with the RO. Paired Student t-test showed prostate volumes (p = 0.008) and midgland areas (p = 0.006) with H mode were significantly smaller than that with B mode. Two-factor analysis of variances showed significant interobserver variability (p < 0.001) in prostate volumes and areas. Inter- and intraobserver consistency was quantified as the standard deviation of mean volumes and areas, and concordance indices. It was found that for small glands (≤35 cc) H mode provided greater interobserver consistency; however, for large glands (≥35 cc), B mode provided more consistent estimates. H mode provided superior inter- and intraobserver agreement in prostate volume definition for small to medium prostates. In large glands, H mode does not exhibit any additional advantage. Although harmonic imaging has not proven advantageous for all cases, its utilization seems to be judicious for small prostates. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

  12. The regulation of adiponectin receptors in human prostate cancer cell lines

    SciTech Connect

    Mistry, T.; Digby, J.E.; Chen, J.; Desai, K.M.; Randeva, H.S. . E-mail: H.Randeva@warwick.ac.uk

    2006-09-29

    Obesity is a risk factor for prostate cancer, and plasma levels of the adipokine, adiponectin, are low in the former but high in the latter. Adiponectin has been shown to modulate cell proliferation and apoptosis, suggesting that adiponectin and its receptors (Adipo-R1, Adipo-R2) may provide a molecular association between obesity and prostate carcinogenesis. We show for First time, the protein distribution of Adipo-R1 and Adipo-R2 in LNCaP and PC3 cells, and in human prostate tissue. Using real-time RT-PCR we provide novel data demonstrating the differential regulation of Adipo-R1 and Adipo-R2 mRNA expression by testosterone, 5-{alpha} dihydrotestosterone, {beta}-estradiol, tumour necrosis factor-{alpha}, leptin, and adiponectin in LNCaP and PC3 cells. Our findings suggest that adiponectin and its receptors may contribute to the molecular association between obesity and prostate cancer through a complex interaction with other hormones and cytokines that also play important roles in the pathophysiology of obesity and prostate cancer.

  13. Mapping MRI/MRS Parameters with Genetic Over-expression Profiles In Human Prostate Cancer: Demonstrating the Potential

    PubMed Central

    Lenkinski, Robert E.; Bloch, B. Nicholas; Liu, Fangbing; Frangioni, John V.; Perner, Sven; Rubin, Mark A.; Genega, Elizabeth; Rofsky, Neil M.; Gaston, Sandra M.

    2009-01-01

    Magnetic resonance imaging (MRI) and MR spectroscopy can probe a variety of physiological (e.g. blood vessel permeability) and metabolic characteristics of prostate cancer. However, little is known about the changes in gene expression that underlie the spectral and imaging features observed in prostate cancer. Tumor induced changes in vascular permeability and angiogenesis are thought to contribute to patterns of dynamic contrast enhanced (DCE) MRI images of prostate cancer even though the genetic basis of tumor vasculogenesis is complex and the specific mechanisms underlying these DCEMRI features have not yet been determined. In order to identify the changes in gene expression that correspond to MRS and DCEMRI patterns in human prostate cancers, we have utilized tissue print micropeel techniques to generate “whole mount” molecular maps of radical prostatectomy specimens that correspond to pre-surgical MRI/MRS studies. These molecular maps include RNA expression profiles from both Affymetrix GeneChip microarrays and quantitative reverse transcriptase PCR (qrt-PCR) analysis, as well as immunohistochemical studies. Using these methods on patients with prostate cancer, we found robust over-expression of choline kinase a in the majority of primary tumors. We also observed overexpression of neuropeptide Y (NPY), a newly identified angiogenic factor, in a subset of DCEMRI positive prostate cancers. These studies set the stage for establishing MRI/MRS parameters as validated biomarkers for human prostate cancer. PMID:18752015

  14. Quantification of Mesenchymal Stem Cells (MSCs) at sites of human prostate cancer.

    PubMed

    Brennen, W Nathaniel; Chen, Shuangling; Denmeade, Samuel R; Isaacs, John T

    2013-01-01

    Circulating bone marrow-derived Mesenchymal Stem Cells (BM-MSCs) have an innate tropism for tumor tissue in response to the inflammatory microenvironment present in malignant lesions. The prostate is bombarded by numerous infectious and inflammatory insults over a lifetime. Chronic inflammation is associated with CXCL12, CCL5, and CCL2, which are highly overexpressed in prostate cancer. Among other cell types, these chemoattractant stimuli recruit BM-MSCs to the tumor. MSCs are minimally defined as plastic-adhering cells characterized by the expression of CD90, CD73, and CD105 in the absence of hematopoietic markers, which can differentiate into osteoblasts, chondrocytes, and adipocytes. MSCs are immunoprivileged and have been implicated in tumorigenesis through multiple mechanisms, including promoting proliferation, angiogenesis, and metastasis, in addition to the generation of an immunosuppressive microenvironment. We have demonstrated that MSCs represent 0.01-1.1% of the total cells present in core biopsies from primary human prostatectomies. Importantly, these analyses were performed on samples prior to expansion in tissue culture. MSCs in these prostatectomy samples are FAP-, CD90-, CD73-, and CD105-positive, and CD14-, CD20-, CD34-, CD45-, and HLA-DR-negative. Additionally, like BM-MSCs, these prostate cancer-derived stromal cells (PrCSCs) were shown to differentiate into osteoblasts, adipocytes and chondrocytes. In contrast to primary prostate cancer-derived epithelial cells, fluorescently-labeled PrCSCs and BM-MSCs were both shown to home to CWR22RH prostate cancer xenografts following IV injection. These studies demonstrate that not only are MSCs present in sites of prostate cancer where they may contribute to carcinogenesis, but these cells may also potentially be used to deliver cytotoxic or imaging agents for therapeutic and/or diagnostic purposes.

  15. Blood and tissue biomarkers in prostate cancer: state of the art.

    PubMed

    Fiorentino, Michelangelo; Capizzi, Elisa; Loda, Massimo

    2010-02-01

    The prevalence of prostate cancer (PCa) is high and increases with age. PCa is the most common cutaneous cancer in American men. Prostate-specific antigen (PSA) screening has impacted the detection of PCa and is directly responsible for a dramatic decrease in stage at diagnosis. Gleason score and stage at the time of diagnosis remain the mainstay to predict prognosis, in the absence of more accurate and reliable tissue or blood biomarkers. Despite extensive research efforts, very few biomarkers of PCa have been introduced to date in clinical practice. Even screening with PSA has recently been questioned. A thorough analysis of all tissue and serum biomarkers in prostate cancer research cannot be easily synthesized, and goes beyond the scope of the present article. Therefore the authors focus here on the most recently reported tissue and circulating biomarkers for PCa whose application in clinical practice is either current or expected in the near future.

  16. High-Resolution Radioluminescence Microscopy for the Study of Prostate Tissue Slice Cell Metabolism and Monitoring of Treatment Response

    DTIC Science & Technology

    2015-09-01

    a few cells) image of the local metabolism in prostate cancer tissue slice cultures (TSCs). Our hypothesis is that the local glucose concentration in...prostate TSCs is correlated to the malignancy of the disease. We aim at developing a microscopy technology to image the uptake of radiotracers into...5 Objective 1: Design of a radioluminescence microscope for the imaging of FDG uptake in prostate tissue slice cultures (TSCs

  17. Aberrant hypomethylation-mediated CD147 overexpression promotes aggressive tumor progression in human prostate cancer.

    PubMed

    Liang, Yu-Xiang; Mo, Ru-Jun; He, Hui-Chan; Chen, Jia-Hong; Zou, Jun; Han, Zhao-Dong; Lu, Jian-Ming; Cai, Chao; Zeng, Yan-Ru; Zhong, Wei-De; Wu, Chin-Lee

    2015-05-01

    Our previous study revealed the potential role of CD147 in human prostate cancer (PCa). Here, we investigated the CD147 promoter methylation status and the correlation with tumorigenicity in human PCa. CD147 mRNA and protein expression levels were both significantly higher in the 4 PCa cell lines, than in the 2 non-tumorigenic benign human prostatic epithelial cell lines (all P<0.01). We showed hypomethylation of promoter regions of CD147 in PCa cell lines with significant CD147 expression as compared to non-tumorigenic benign human prostatic epithelial cell lines slowly expressing CD147. Additionally, the treatment of methylated cell lines with 5-aza-2'-deoxycytidine increased CD147 expression significantly in low-expressing cell lines and also activated the expression of matrix metalloproteinase (MMP)-2, which may be one of the most important downstream targets of CD147. Furthermore, PCa tissues displayed decreased DNA methylation in the promoter region of CD147 compared to the corresponding non-cancerous prostate tissues, and methylation intensity correlated inversely with the CD147 mRNA levels. There was a significant negative correlation between CD147 mRNA levels and the number of methylated sites in PCa tissues (r=-0.467, P<0.01). In conclusion, our data offer convincing evidence for the first time that the DNA promoter hypomethylation of CD147 may be one of the regulatory mechanisms involved in the cancer-related overexpression of CD147 and may play a crucial role in the tumorigenesis of PCa.

  18. Trans-urethral ultrasound (TUUS) imaging for visualization and analysis of the prostate and associated tissues.

    PubMed

    Holmes, D R; Robb, R

    2000-01-01

    The incidence of prostate disease is high. However, accurate assessment of pathological conditions is still difficult. Although CT, MRI, and TRUS imaging methods provide useful information, each has specific drawbacks. Our work examines the potential and utility of 3D trans-urethral ultrasound (TUUS) for improved imaging of the prostate. Four normal canines were examined with TUUS. The catheter was placed in the urethra and used to image the prostate, rectum, bladder, ureter, neuro-vascular bundles, arteries, and surrounding tissue. 2D and 3D datasets were acquired and digitized. The 2D data provides useful visualization of the tissue. The clinician was also able to watch urine enter the bladder and perform a digital rectal exam in real-time. 3D data visualization required torodial reconstruction. The algorithm was optimized to provide very fast 3D reconstructions of the prostate. Segmentation of the data proved challenging, but 3D visualization, including volume rendered data and surface rendered data, were well accepted by clinicians. Clinicians and researchers determined a number of potential applications of these new techniques, including: prostate cancer diagnosis and staging, assessment of Benign Nodular Enlargement, assessment of physiologic function of the bladder, evaluation of morphologic properties of the prostate, and image guided biopsy and therapy.

  19. Hypermethylation of CpG islands in primary and metastatic human prostate cancer.

    PubMed

    Yegnasubramanian, Srinivasan; Kowalski, Jeanne; Gonzalgo, Mark L; Zahurak, Marianna; Piantadosi, Steven; Walsh, Patrick C; Bova, G Steven; De Marzo, Angelo M; Isaacs, William B; Nelson, William G

    2004-03-15

    Aberrant DNA methylation patterns may be the earliest somatic genome changes in prostate cancer. Using real-time methylation-specific PCR, we assessed the extent of hypermethylation at 16 CpG islands in DNA from seven prostate cancer cell lines (LNCaP, PC-3, DU-145, LAPC-4, CWR22Rv1, VCaP, and C42B), normal prostate epithelial cells, normal prostate stromal cells, 73 primary prostate cancers, 91 metastatic prostate cancers, and 25 noncancerous prostate tissues. We found that CpG islands at GSTP1, APC, RASSF1a, PTGS2, and MDR1 were hypermethylated in >85% of prostate cancers and cancer cell lines but not in normal prostate cells and tissues; CpG islands at EDNRB, ESR1, CDKN2a, and hMLH1 exhibited low to moderate rates of hypermethylation in prostate cancer tissues and cancer cell lines but were entirely unmethylated in normal tissues; and CpG islands at DAPK1, TIMP3, MGMT, CDKN2b, p14/ARF, and CDH1 were not abnormally hypermethylated in prostate cancers. Receiver operator characteristic curve analyses suggested that CpG island hypermethylation changes at GSTP1, APC, RASSF1a, PTGS2, and MDR1 in various combinations can distinguish primary prostate cancer from benign prostate tissues with sensitivities of 97.3-100% and specificities of 92-100%. Hypermethylation of the CpG island at EDNRB was correlated with the grade and stage of the primary prostate cancers. PTGS2 CpG island hypermethylation portended an increased risk of recurrence. Furthermore, CpG island hypermethylation patterns in prostate cancer metastases were very similar to the primary prostate cancers and tended to show greater differences between cases than between anatomical sites of metastasis.

  20. [Prostate cancer detection by assessing stiffness of different tissues using shear wave ultrasound elastog- raphy].

    PubMed

    Glybochko, P V; Alyaev, Yu G; Amosov, A V; Krupinov, G E; Ganzha, T M; Vorobev, A V; Lumpov, I S; Semendyaev, R I

    2016-08-01

    Early detection of prostate cancer (PCa) remains a challenging issue. There are studies underway aimed to develop and implement new methods for prostate cancer screening by tumor imaging and obtaining tissue samples from suspicious areas for morphological examination. One of these new methods is shear wave ultrasound elastography (SWUE). The current literature is lacking sufficient coverage of informativeness and specificity of SWUE in the prostate cancer detection, there is no clear criteria for assessing tissue stiffness at different values of PSA and tumor grade, and in prostate hyperplasia and prostatitis. To evaluate the informativeness and specificity of SWUE compared with other diagnostic methods. SWUE has been used in the Clinic of Urology of Sechenov First MSMU since October 2015. During this period, 302 patients were examined using SWUE. SWUE was performed with Aixplorer ultrasound system (Super Sonic Imagine), which provides a single-stage SWUE imaging with both B-mode and real-time mode. The first group (prospective study) included 134 men aged 47 to 81 years with suspected prostate cancer scheduled to either initial or repeat prostate biopsy. PSA levels ranged from 4 to 24 ng/ml. The second group (retrospective study) comprised 120 men with confirmed prostate cancer and PSA levels between 4 and 90 ng/ml. The third group (the control group), comprised 48 healthy men whose PSA level did not exceed 3 ng/ml. All patients of the groups 1 and 2 underwent a standard comprehensive examination. Patients in group 1 were subsequently subjected to transrectal prostate biopsy guided by localization of areas with abnormal tissue stiffness. PCa was detected in 100 of 134 patients. 217 patients of groups 1 and 2 underwent radical prostatectomy. In 28 of them, the match between the cancer location and differentiation in the removed prostate and SWUE findings before surgery was examined. Contrast-enhanced magnetic resonance imaging of pelvic organs was performed in 63

  1. Trans-urethral ultrasound (TUUS) imaging for visualization and analysis of the prostate and associated tissues

    NASA Astrophysics Data System (ADS)

    Holmes, David R., III; Robb, Richard A.

    2000-04-01

    Accurate assessment of pathological conditions in the prostate is difficult. Screening methods include palpation if the prostate gland, blood chemical testing, and diagnostic imaging. Trans-rectal Ultrasound (TRUS) is commonly used for the assessment of pathological conditions, however, TRUS is severely constrained by the relative distal location of the imaging probe. Trans-urethral Ultrasound (TUUS) may overcome some limitations of TRUS. A TUUS catheter was used to image the prostate, rectum, bladder, ureter, neuro-vascular bundles, arteries, and surrounding tissue. In addition, 360 degrees rotational scans were recorded for reconstruction into 3D volumes. Segmentation was challenging, however, new techniques such as active contour methods show potential. 3D visualizations, including both volume and surface rendering, were provided to clinicians off-line. On-line 3D visualization techniques are currently being developed. Potential applications of TUUS include: prostate cancer diagnosis and staging as well as image guided biopsy and therapy.

  2. Capillary Force Seeding of Sphere-Templated Hydrogels for Tissue-Engineered Prostate Cancer Xenografts

    PubMed Central

    Long, Thomas J.; Takeno, Marc; Sprenger, Cynthia C.; Plymate, Stephen R.

    2013-01-01

    Biomaterial-based tissue-engineered tumor models are now widely used in cancer biology studies. However, specific methods for efficient and reliable cell seeding into these and tissue-engineering constructs used for regenerative medicine often remain poorly defined. Here, we describe a capillary force-based method for seeding the human prostate cancer cell lines M12 and LNCaP C4-2 into sphere-templated poly(2-hydroxyethyl methacrylate) hydrogels. The capillary force seeding method improved the cell number and distribution within the porous scaffolds compared to well-established protocols such as static and centrifugation seeding. Seeding efficiency was found to be strongly dependent on the rounded cell diameter relative to the pore diameter and pore interconnect size, parameters that can be controllably modulated during scaffold fabrication. Cell seeding efficiency was evaluated quantitatively using a PicoGreen DNA assay, which demonstrated some variation in cell retention using the capillary force method. When cultured within the porous hydrogels, both cell lines attached and proliferated within the network, but histology showed the formation of a necrotic zone by 7 days likely due to oxygen and nutrient diffusional limitations. The necrotic zone thickness was decreased by dynamically culturing cells in an orbital shaker. Proliferation analysis showed that despite a variable seeding efficiency, by 7 days in culture, scaffolds contained a roughly consistent number of cells as they proliferated to fill the pores of the scaffold. These studies demonstrate that sphere-templated polymeric scaffolds have the potential to serve as an adaptable cell culture substrate for engineering a three-dimensional prostate cancer model. PMID:23373788

  3. Vitamin D Receptor Protein Expression in Tumor Tissue and Prostate Cancer Progression

    PubMed Central

    Hendrickson, Whitney K.; Flavin, Richard; Kasperzyk, Julie L.; Fiorentino, Michelangelo; Fang, Fang; Lis, Rosina; Fiore, Christopher; Penney, Kathryn L.; Ma, Jing; Kantoff, Philip W.; Stampfer, Meir J.; Loda, Massimo; Mucci, Lorelei A.; Giovannucci, Edward

    2011-01-01

    Purpose Data suggest that circulating 25-hydroxyvitamin D [25(OH)D] interacts with the vitamin D receptor (VDR) to decrease proliferation and increase apoptosis for some malignancies, although evidence for prostate cancer is less clear. How VDR expression in tumor tissue may influence prostate cancer progression has not been evaluated in large studies. Patients and Methods We examined protein expression of VDR in tumor tissue among 841 patients with prostate cancer in relation to risk of lethal prostate cancer within two prospective cohorts, the Physicians' Health Study and Health Professionals Follow-Up Study. We also examined the association of VDR expression with prediagnostic circulating 25(OH)D and 1,25-dihydroxyvitamin D levels and with two VDR single nucleotide polymorphisms, FokI and BsmI. Results Men whose tumors had high VDR expression had significantly lower prostate-specific antigen (PSA) at diagnosis (P for trend < .001), lower Gleason score (P for trend < .001), and less advanced tumor stage (P for trend < .001) and were more likely to have tumors harboring the TMPRSS2:ERG fusion (P for trend = .009). Compared with the lowest quartile, men whose tumors had the highest VDR expression had significantly reduced risk of lethal prostate cancer (hazard ratio [HR], 0.17; 95% CI, 0.07 to 0.41). This association was only slightly attenuated after adjustment for Gleason score and PSA at diagnosis (HR, 0.33; 95% CI, 0.13 to 0.83) or, additionally, for tumor stage (HR, 0.37; 95% CI, 0.14 to 0.94). Neither prediagnostic plasma vitamin D levels nor VDR polymorphisms were associated with VDR expression. Conclusion High VDR expression in prostate tumors is associated with a reduced risk of lethal cancer, suggesting a role of the vitamin D pathway in prostate cancer progression. PMID:21537045

  4. A double-blind, randomized, neoadjuvant study of the tissue effects of POMx pills in men with prostate cancer before radical prostatectomy.

    PubMed

    Freedland, Stephen J; Carducci, Michael; Kroeger, Nils; Partin, Alan; Rao, Jian-Yu; Jin, Yusheng; Kerkoutian, Susan; Wu, Hong; Li, Yunfeng; Creel, Patricia; Mundy, Kelly; Gurganus, Robin; Fedor, Helen; King, Serina A; Zhang, Yanjun; Heber, David; Pantuck, Allan J

    2013-10-01

    Pomegranates slow prostate cancer xenograft growth and prolong prostate-specific antigen (PSA) doubling times in single-arm human studies. Pomegranates' effects on human prostate tissue are understudied. We hypothesized that orally administered pomegranate extract (POMx; Pom Wonderful) would lower tissue 8-hydroxy-2'-deoxyguanosine (8-OHdG), an oxidative stress biomarker. Seventy men were randomized to two tablets, POMx or placebo, daily up to four weeks before radical prostatectomy. Tissue was analyzed for intraprostatic urolithin A, a pomegranate metabolite, benign and malignant 8-OHdG, and cancer pS6 kinase, NF-κB, and Ki67. Primary endpoint was differences in 8-OHdG, and the study was powered to detect 35% reduction. POMx was associated with 16% lower benign tissue 8-OHdG (P = 0.095), which was not statistically significant. POMx was well tolerated with no treatment-related withdrawals. There were no differences in baseline clinicopathological features between arms. Urolithin A was detected in 21 of the 33 patients in the POMx group versus 12 of the 35 in the placebo group (P = 0.031). Cancer pS6 kinase, NF-κB, Ki67, and serum PSA changes were similar between arms. POMx before surgery results in pomegranate metabolite accumulation in prostate tissues. Our primary endpoint in this modest-sized short-term trial was negative. Future larger longer studies are needed to more definitively test whether POMx reduces prostate oxidative stress, as well as further animal testing to better understand the multiple mechanisms through which POMx may alter prostate cancer biology.

  5. A Double Blind, Randomized, Neoadjuvant Study of the Tissue effects of POMx Pills in Men with Prostate Cancer Prior to Radical Prostatectomy

    PubMed Central

    Freedland, Stephen J.; Carducci, Michael; Kroeger, Nils; Partin, Alan; Rao, Jian-yu; Jin, Yusheng; Kerkoutian, Susan; Wu, Hong; Li, Yunfeng; Creel, Patricia; Mundy, Kelly; Gurganus, Robin; Fedor, Helen; King, Serina A.; Zhang, Yanjun; Heber, David; Pantuck, Allan J.

    2013-01-01

    Pomegranates slow prostate cancer xenograft growth and prolong PSA doubling times in single-arm human studies. Pomegranates’ effects on human prostate tissue are understudied. We hypothesized orally administered pomegranate extract (POMx; PomWonderful, Los Angeles, CA) would lower tissue 8-hydroxy-2-deoxyguanosine (8-OHdG), an oxidative stress biomarker. 70 men were randomized to 2 tablets POMx or placebo daily up to 4 weeks prior to radical prostatectomy. Tissue was analyzed for intra-prostatic Urolithin A, a pomegranate metabolite, benign and malignant 8-OHdG, and cancer pS6 kinase, NFκB, and Ki67. Primary end-point was differences in 8-OHdG powered to detect 30% reduction. POMx was associated with 16% lower benign tissue 8-OHdG (p=0.095), which was not statistically significant. POMx was well-tolerated with no treatment-related withdrawals. There were no differences in baseline clinicopathological features between arms. Urolithin A was detected in 21/33 patient in the POMx group vs. 12/35 in the placebo group (p=0.031). Cancer pS6 kinase, NFκB, Ki67, and serum PSA changes were similar between arms. POMx prior to surgery results in pomegranate metabolite accumulation in prostate tissues. Our primary end-point in this modest-sized short-term trial was negative. Future larger longer studies are needed to more definitely test whether POMx reduces prostate oxidative stress as well as further animal testing to better understand the multiple mechanisms through which POMx may alter prostate cancer biology. PMID:23985577

  6. Dicarbonyl/L-xylulose reductase: a potential biomarker identified by laser-capture microdissection-micro serial analysis of gene expression of human prostate adenocarcinoma.

    PubMed

    Cho-Vega, Jeong Hee; Tsavachidis, Spiridon; Do, Kim-Anh; Nakagawa, Junichi; Medeiros, L Jeffrey; McDonnell, Timothy J

    2007-12-01

    To identify genes involved in prostate carcinogenesis, we used laser-capture microdissection-micro serial analysis of gene expression to construct libraries of paired cancer and normal cells from human tissue samples. After computational comparison of the two libraries, we identified dicarbonyl/l-xylulose reductase (DCXR), an enzyme that catalyzes alpha-dicarbonyl and l-xylulose, as being significantly up-regulated in prostate cancer cells. The specificity of DCXR up-regulation for prostate cancer tissues was confirmed by quantitative real-time reverse transcriptase-PCR, virtual Northern blot, and Western blot analyses. Furthermore, DCXR expression at the protein level was assessed using fresh-frozen tissues and a tissue microarray consisting of 46 cases of organ-confined early-stage prostate cancer and 29 cases of chemohormonally treated prostate cancer. In most normal prostate epithelial cells, DCXR was expressed at low levels and was localized predominantly in the cytoplasmic membrane. In contrast, in virtually all grades of early-stage prostate cancer and in all chemohormonally treated cases, DCXR was strikingly overexpressed and was localized predominantly in the cytoplasm and nucleus. In all samples, the stromal cells were completely devoid of DCXR expression. Based on these findings, we suggest that DCXR overexpression has the potential to be an additional useful biomarker for prostate cancer.

  7. Online Image-based Monitoring of Soft-tissue Displacements for Radiation Therapy of the Prostate

    SciTech Connect

    Schlosser, Jeffrey; Salisbury, Kenneth; Hristov, Dimitre

    2012-08-01

    Purpose: Emerging prolonged, hypofractionated radiotherapy regimens rely on high-dose conformality to minimize toxicity and thus can benefit from image guidance systems that continuously monitor target position during beam delivery. To address this need we previously developed, as a potential add-on device for existing linear accelerators, a novel telerobotic ultrasound system capable of real-time, soft-tissue imaging. Expanding on this capability, the aim of this work was to develop and characterize an image-based technique for real-time detection of prostate displacements. Methods and Materials: Image processing techniques were implemented on spatially localized ultrasound images to generate two parameters representing prostate displacements in real time. In a phantom and five volunteers, soft-tissue targets were continuously imaged with a customized robotic manipulator while recording the two tissue displacement parameters (TDPs). Variations of the TDPs in the absence of tissue displacements were evaluated, as was the sensitivity of the TDPs to prostate translations and rotations. Robustness of the approach to probe force was also investigated. Results: With 95% confidence, the proposed method detected in vivo prostate displacements before they exceeded 2.3, 2.5, and 2.8 mm in anteroposterior, superoinferior, and mediolateral directions. Prostate pitch was detected before exceeding 4.7 Degree-Sign at 95% confidence. Total system time lag averaged 173 ms, mostly limited by ultrasound acquisition rate. False positives (FPs) (FP) in the absence of displacements did not exceed 1.5 FP events per 10 min of continuous in vivo imaging time. Conclusions: The feasibility of using telerobotic ultrasound for real-time, soft-tissue-based monitoring of target displacements was confirmed in vivo. Such monitoring has the potential to detect small clinically relevant intrafractional variations of the prostate position during beam delivery.

  8. The Isolation and Characterization of Human Prostate Cancer Stem Cells

    DTIC Science & Technology

    2012-02-01

    magnetic field.1 This technique is based on the cellular uptake and magnetic levitation of a...culture based on magnetic cell levitation . Nature nanotechnology;5(4):291-6. Appendix None. ...have focused attention on two alternative strategies: magnetic nanoparticles and human prostate fibroblasts

  9. The human retrovirus XMRV in prostate cancer and chronic fatigue syndrome.

    PubMed

    Silverman, Robert H; Nguyen, Carvell; Weight, Christopher J; Klein, Eric A

    2010-07-01

    Xenotropic murine leukemia virus-related virus (XMRV) is an authentic, newly recognized human retrovirus first identified in prostate cancer tissues from men with a deficiency in the innate immunity gene RNASEL. At present, studies have detected XMRV at widely different rates in prostate cancer cases (0-27%) and in patients with chronic fatigue syndrome (CFS; 0-67%). Indirect or direct modes of carcinogenesis by XMRV have been suggested depending on whether the virus was found in stroma or malignant epithelium. Viral replication in the prostate might be affected by androgens, which stimulate XMRV through a transcriptional enhancer site in viral DNA. By contrast, host restriction factors, such as APOBEC3 and tetherin, inhibit virus replication. Immune dysfunction mediated by XMRV has been suggested as a possible factor in CFS. Recent studies show that some existing antiretroviral drugs suppress XMRV infections and diagnostic assays are under development. Although other retroviruses of the same genus as XMRV (gammaretroviruses) cause cancer and neurological disease in animals, whether XMRV is a cause of either prostate cancer or CFS remains unknown. Emerging science surrounding XMRV is contributing to our knowledge of retroviral infections while focusing intense interest on two major human diseases.

  10. FGFR1-WNT-TGF-β signaling in prostate cancer mouse models recapitulates human reactive stroma

    PubMed Central

    Carstens, Julienne L.; Shahi, Payam; Van Tsang, Susan; Smith, Billie; Creighton, Chad J.; Zhang, Yiqun; Seamans, Amber; Seethammagari, Mamatha; Vedula, Indira; Levitt, Jonathan M.; Ittmann, Michael M.; Rowley, David R.; Spencer, David M.

    2014-01-01

    The reactive stroma surrounding tumor lesions performs critical roles ranging from supporting tumor cell proliferation to inducing tumorigenesis and metastasis. Therefore, it is critical to understand the cellular components and signaling control mechanisms that underlay the etiology of reactive stroma. Previous studies have individually implicated fibroblast growth factor receptor 1 (FGFR1) and canonical WNT/β-catenin signaling in prostate cancer progression and the initiation and maintenance of a reactive stroma; however, both pathways are frequently found co-activated in cancer tissue. Using autochthonous transgenic mouse models for inducible FGFR1 (JOCK1) and prostate-specific and ubiquitously expressed inducible β-catenin (Pro-Cat and Ubi-Cat, respectively) and bigenic crosses between these lines (Pro-Cat × JOCK1 and Ubi-Cat × JOCK1), we describe WNT-induced synergistic acceleration of FGFR1-driven adenocarcinoma, associated with a pronounced fibroblastic reactive stroma activation surrounding prostatic intraepithelial neoplasia (mPIN) lesions found both in situ and reconstitution assays. Both mouse and human reactive stroma exhibited increased transforming growth factor-beta (TGF-β) signaling adjacent to pathologic lesions likely contributing to invasion. Furthermore, elevated stromal TGF-β signaling was associated with higher Gleason scores in archived human biopsies, mirroring murine patterns. Our findings establish the importance of the FGFR1-WNT-TGF-β signaling axes as driving forces behind reactive stroma in aggressive prostate adenocarcinomas, deepening their relevance as therapeutic targets. PMID:24305876

  11. Quantitative RT-PCR analysis of estrogen receptor gene expression in laser microdissected prostate cancer tissue.

    PubMed

    Walton, Thomas J; Li, Geng; McCulloch, Thomas A; Seth, Rashmi; Powe, Desmond G; Bishop, Michael C; Rees, Robert C

    2009-06-01

    Real-time quantitative RT-PCR analysis of laser microdissected tissue is considered the most accurate technique for determining tissue gene expression. The discovery of estrogen receptor beta (ERbeta) has focussed renewed interest on the role of estrogen receptors in prostate cancer, yet few studies have utilized the technique to analyze estrogen receptor gene expression in prostate cancer. Fresh tissue was obtained from 11 radical prostatectomy specimens and from 6 patients with benign prostate hyperplasia. Pure populations of benign and malignant prostate epithelium were laser microdissected, followed by RNA isolation and electrophoresis. Quantitative RT-PCR was performed using primers for androgen receptor (AR), estrogen receptor beta (ERbeta), estrogen receptor alpha (ERalpha), progesterone receptor (PGR) and prostate specific antigen (PSA), with normalization to two housekeeping genes. Differences in gene expression were analyzed using the Mann-Whitney U-test. Correlation coefficients were analyzed using Spearman's test. Significant positive correlations were seen when AR and AR-dependent PSA, and ERalpha and ERalpha-dependent PGR were compared, indicating a representative population of RNA transcripts. ERbeta gene expression was significantly over-expressed in the cancer group compared with benign controls (P < 0.01). In contrast, PGR expression was significantly down-regulated in the cancer group (P < 0.05). There were no significant differences in AR, ERalpha or PSA expression between the groups. This study represents the first to show an upregulation of ERbeta gene expression in laser microdissected prostate cancer specimens. In concert with recent studies the findings suggest differential production of ERbeta splice variants, which may play important roles in the genesis of prostate cancer. (c) 2009 Wiley-Liss, Inc.

  12. Radiation Effect on Human Tissue

    NASA Technical Reports Server (NTRS)

    Richmond, Robert C.; Cruz, Angela; Bors, Karen; Curreri, Peter A. (Technical Monitor)

    2002-01-01

    Predicting the occurrence of human cancer following exposure of an epidemiologic population to any agent causing genetic damage is a difficult task. To an approximation, this is because the uncertainty of uniform exposure to the damaging agent, and the uncertainty of uniform processing of that damage within a complex set of biological variables, degrade the confidence of predicting the delayed expression of cancer as a relatively rare event within clinically normal individuals. This situation begs the need for alternate controlled experimental models that are predictive for the development of human cancer following exposures to agents causing genetic damage. Such models historically have not been of substantial proven value. It is more recently encouraging, however, that developments in molecular and cell biology have led to an expanded knowledge of human carcinogenesis, and of molecular markers associated with that process. It is therefore appropriate to consider new laboratory models developed to accomodate that expanded knowledge in order to assess the cancer risks associated with exposures to genotoxic agents. When ionizing radiation of space is the genotoxic agent, then a series of additional considerations for human cancer risk assessment must also be applied. These include the dose of radiation absorbed by tissue at different locations in the body, the quality of the absorbed radiation, the rate at which absorbed dose accumulates in tissue, the way in which absorbed dose is measured and calculated, and the alterations in incident radiation caused by shielding materials. It is clear that human cancer risk assessment for damage caused by ionizing radiation is a multidisciplinary responsibility, and that within this responsibility no single discipline can hold disproportionate sway if a risk assessment model of radiation-induced human cancer is to be developed that has proven value. Biomolecular and cellular markers from the work reported here are considered

  13. Radiation Effect on Human Tissue

    NASA Technical Reports Server (NTRS)

    Richmond, Robert C.; Cruz, Angela; Bors, Karen; Curreri, Peter A. (Technical Monitor)

    2002-01-01

    Predicting the occurrence of human cancer following exposure of an epidemiologic population to any agent causing genetic damage is a difficult task. To an approximation, this is because the uncertainty of uniform exposure to the damaging agent, and the uncertainty of uniform processing of that damage within a complex set of biological variables, degrade the confidence of predicting the delayed expression of cancer as a relatively rare event within clinically normal individuals. This situation begs the need for alternate controlled experimental models that are predictive for the development of human cancer following exposures to agents causing genetic damage. Such models historically have not been of substantial proven value. It is more recently encouraging, however, that developments in molecular and cell biology have led to an expanded knowledge of human carcinogenesis, and of molecular markers associated with that process. It is therefore appropriate to consider new laboratory models developed to accomodate that expanded knowledge in order to assess the cancer risks associated with exposures to genotoxic agents. When ionizing radiation of space is the genotoxic agent, then a series of additional considerations for human cancer risk assessment must also be applied. These include the dose of radiation absorbed by tissue at different locations in the body, the quality of the absorbed radiation, the rate at which absorbed dose accumulates in tissue, the way in which absorbed dose is measured and calculated, and the alterations in incident radiation caused by shielding materials. It is clear that human cancer risk assessment for damage caused by ionizing radiation is a multidisciplinary responsibility, and that within this responsibility no single discipline can hold disproportionate sway if a risk assessment model of radiation-induced human cancer is to be developed that has proven value. Biomolecular and cellular markers from the work reported here are considered

  14. Microbiota of Human Breast Tissue

    PubMed Central

    Urbaniak, Camilla; Cummins, Joanne; Brackstone, Muriel; Macklaim, Jean M.; Gloor, Gregory B.; Baban, Chwanrow K.; Scott, Leslie; O'Hanlon, Deidre M.; Burton, Jeremy P.; Francis, Kevin P.; Tangney, Mark

    2014-01-01

    In recent years, a greater appreciation for the microbes inhabiting human body sites has emerged. In the female mammary gland, milk has been shown to contain bacterial species, ostensibly reaching the ducts from the skin. We decided to investigate whether there is a microbiome within the mammary tissue. Using 16S rRNA sequencing and culture, we analyzed breast tissue from 81 women with and without cancer in Canada and Ireland. A diverse population of bacteria was detected within tissue collected from sites all around the breast in women aged 18 to 90, not all of whom had a history of lactation. The principal phylum was Proteobacteria. The most abundant taxa in the Canadian samples were Bacillus (11.4%), Acinetobacter (10.0%), Enterobacteriaceae (8.3%), Pseudomonas (6.5%), Staphylococcus (6.5%), Propionibacterium (5.8%), Comamonadaceae (5.7%), Gammaproteobacteria (5.0%), and Prevotella (5.0%). In the Irish samples the most abundant taxa were Enterobacteriaceae (30.8%), Staphylococcus (12.7%), Listeria welshimeri (12.1%), Propionibacterium (10.1%), and Pseudomonas (5.3%). None of the subjects had signs or symptoms of infection, but the presence of viable bacteria was confirmed in some samples by culture. The extent to which these organisms play a role in health or disease remains to be determined. PMID:24610844

  15. SEM and X-ray microanalysis of human prostatic calculi

    SciTech Connect

    Vilches, J.; Lopez, A.; De Palacio, L.; Munoz, C.; Gomez, J.

    1982-02-01

    Calculi removed from human prostates affected with nodular hyperplasia were analyzed with scanning electron microscopy and EDAX system. The general spectrum was made up of Na, Al, Mg, S, P, Ca and Zn. Two types of stone were identified morphostructurally and microanalytically: calculi type I of nodular surface with high peaks of S, and calculi type II polyfaceted with high peaks of P and Ca. Their formation from corpora amylacea and/or exogenous constituents is discussed. The superficial deposit of Zn suggests its incorporation from the prostatic liquid and does not seem to play an important role in the genesis.

  16. Potential Prognostic Markers for Human Prostate Cancer

    DTIC Science & Technology

    2001-03-01

    such as proliferation, differentiation and assay [15]. TGF[3 may be produced by metastatic motility. Upregulation of growth factor synthesis or prostate...via mod- ronment include neuroendocrine cells. These cells ulation of tumor cell receptor expression. Control of can secrete bombesin, a gastrin ...controls, indicating that addition ofT015 accelerates tumor expansion. TIl15 synthesis triggered a dramatic increase in cell motility, boosting serum

  17. Expression of the human relaxin gene in the corpus luteum of the menstrual cycle and in the prostate.

    PubMed

    Ivell, R; Hunt, N; Khan-Dawood, F; Dawood, M Y

    1989-10-01

    DNA-RNA hybridization has been used to assess the presence of relaxin gene transcripts in human luteal tissues of pregnancy and the menstrual cycle, as well as in the human testis and prostate. The results imply a substantial capacity for hormone biosynthesis in the mid to late luteal phase of the ovary in non-pregnant women. In men the prostate has been shown also to express relaxin gene transcripts, though levels are low. The testis appears negative. The results suggest that functions for relaxin must be sought also outside pregnancy.

  18. Telomerase as an Androgen Receptor-Regulated Target in Selenium Chemoprevention of Prostate Cancer

    DTIC Science & Technology

    2009-05-01

    samples and in all human prostate cancer cell lines, but not in normal or benign prostatic hyperplasia tissues (1-5). The inhibition of telomerase by...clinical implications. Telomerase activation has been reported in >90% of prostate cancer samples, but not in normal or benign prostatic hyperplasia tissues

  19. Resonance sensor measurements of stiffness variations in prostate tissue in vitro--a weighted tissue proportion model.

    PubMed

    Jalkanen, Ville; Andersson, Britt M; Bergh, Anders; Ljungberg, Börje; Lindahl, Olof A

    2006-12-01

    Prostate cancer is the most common type of cancer in men in Europe and the US. The methods to detect prostate cancer are still precarious and new techniques are needed. A piezoelectric transducer element in a feedback system is set to vibrate with its resonance frequency. When the sensor element contacts an object a change in the resonance frequency is observed, and this feature has been utilized in sensor systems to describe physical properties of different objects. For medical applications it has been used to measure stiffness variations due to various patho-physiological conditions. In this study the sensor's ability to measure the stiffness of prostate tissue, from two excised prostatectomy specimens in vitro, was analysed. The specimens were also subjected to morphometric measurements, and the sensor parameter was compared with the morphology of the tissue with linear regression. In the probe impression interval 0.5-1.7 mm, the maximum R(2) > or = 0.60 (p < 0.05, n = 75). An increase in the proportion of prostate stones (corpora amylacea), stroma, or cancer in relation to healthy glandular tissue increased the measured stiffness. Cancer and stroma had the greatest effect on the measured stiffness. The deeper the sensor was pressed, the greater, i.e., deeper, volume it sensed. Tissue sections deeper in the tissue were assigned a lower mathematical weighting than sections closer to the sensor probe. It is concluded that cancer increases the measured stiffness as compared with healthy glandular tissue, but areas with predominantly stroma or many stones could be more difficult to differ from cancer.

  20. Elevated expression of HIF-lα in actively growing prostate tissues is associated with clinical features of benign prostatic hyperplasia

    PubMed Central

    Li, Xin; Wang, Hui; Liu, Shuai; Wu, Haihu; Bi, Dongbin; Ding, Kejia; Lu, Jiaju

    2016-01-01

    Background Benign prostatic hyperplasia (BPH) is one of the most common diseases in middle-age or older men. Increasing evidence has shown that BPH is associated with hypoxia microenvironment. Methods We retrospectively collected patient data and tissue samples from fetal prostates(FP), normal prostates(NP), intra-acinar of BPH, peri-acinar of BPH, prostate cancers and sarcomas of prostate. The expression of HIF-1α, as well as VEGF was visualized by immunohistochemistry and statistically analyzed with clinical parameters. Results Expression of HIF-lα was observed in intra-acinar of BPH (69.5%), prostate cancer (85.7%) and all FPs, while NP and peri-acinar of BPH tissues were all stained negative. HIF-lα levels in FPs and the malignant tumors were higher than BPH tissues(p < 0.05), and the expression of HIF-lα in intra-acinar of BPH was higher than NP and peri-acinar of BPH (p < 0.05). The expression of HIF-lα was correlated with the weight of intra-acinar of prostate (p < 0.05). And patients with prostate weight larger that 72.45g were prone to have HIF-lα moderate-positive expression, according to the ROC curve (AUC = 0.734, 95%CI = 0.630-0.838). Moreover, the risk of acute urine retention (AUR) for HIF-lα moderate-positive patients increased significantly (OR=5.517, 95%CI = 2.434-12.504). Conclusions HIF-lα expression is increased in highly proliferative prostate tissues and correlated with the weight of intra-acinar prostate. Moreover, HIF-lα is also an independent risk factor for AUR occurrence in BPH patients. PMID:26919249

  1. Linking obesogenic dysregulation to prostate cancer progression

    PubMed Central

    Taylor, Renea A; Lo, Jennifer; Ascui, Natasha; Watt, Matthew J

    2015-01-01

    The global epidemic of obesity is closely linked to the development of serious co-morbidities, including many forms of cancer. Epidemiological evidence consistently shows that obesity is associated with a similar or mildly increased incidence of prostate cancer but, more prominently, an increased risk for aggressive prostate cancer and prostate cancer-specific mortality. Studies in mice demonstrate that obesity induced by high-fat feeding increases prostate cancer progression; however, the mechanisms underpinning this relationship remain incompletely understood. Adipose tissue expansion in obesity leads to local tissue dysfunction and is associated with low-grade inflammation, alterations in endocrine function and changes in lipolysis that result in increased delivery of fatty acids to tissues of the body. The human prostate gland is covered anteriorly by the prominent peri-prostatic adipose tissue and laterally by smaller adipose tissue depots that lie directly adjacent to the prostatic surface. We discuss how the close association between dysfunctional adipose tissue and prostate epithelial cells might result in bi-directional communication to cause increased prostate cancer aggressiveness and progression. However, the literature indicates that several ‘mainstream’ hypotheses regarding obesity-related drivers of prostate cancer progression are not yet supported by a solid evidence base and, in particular, are not supported by experiments using human tissue. Understanding the links between obesity and prostate cancer will have major implications for the health policy for men with prostate cancer and the development of new therapeutic or preventative strategies. PMID:26581226

  2. Differential expression of a human kallikrein 5 (KLK5) splice variant in ovarian and prostate cancer.

    PubMed

    Kurlender, Lisa; Yousef, George M; Memari, Nader; Robb, John-Desmond; Michael, Iacovos P; Borgoño, Carla; Katsaros, Dionyssios; Stephan, Carsten; Jung, Klaus; Diamandis, Eleftherios P

    2004-01-01

    The presence of more than one mRNA form is common among kallikrein genes. We identified an mRNA transcript of the human kallikrein gene 5 (KLK5), denoted KLK5 splice variant 1 (KLK5-SV1). This variant has a different 5'-splice site, but encodes the same protein as the classical KLK5 transcript. RT-PCR analysis of this variant transcript expression in 29 human tissues indicated highest expression in the cervix, salivary gland, kidney, mammary gland, and skin. Comparative analysis of the expression levels of KLK5-SV1, another splice variant named KLK5 splice variant 2 (KLK5-SV2), and the classical KLK5 form showed that out of all three mRNA transcripts, the classical form is predominantly expressed (found in more tissues and at higher expression levels) followed by KLK5-SV1. KLK5-SV1 is expressed at high levels in ovarian, pancreatic, breast and prostate cancer cell lines. KLK5-SV1 was also found to be expressed in 9/10 ovarian cancer tissues, but it was not found in one normal ovarian tissue tested. Hormonal regulation experiments suggest that KLK5-SV1 is regulated by steroid hormones in the BT-474 breast cancer cell line. Furthermore, this variant had significantly higher expression in normal prostate tissues compared to their matched cancer tissue counterparts. KLK5-SV1 may have clinical utility in various malignancies and should be further explored as a potential new biomarker for prostate and ovarian cancer.

  3. Inhibition of microRNA-500 has anti-cancer effect through its conditional downstream target of TFPI in human prostate cancer.

    PubMed

    Cai, Bing; Chen, Wei; Pan, Yue; Chen, Hongde; Zhang, Yirong; Weng, Zhiliang; Li, Yeping

    2017-07-01

    We investigated the prognostic potential and regulatory mechanism of microRNA-500 (miR-500), and human gene of tissue factor pathway inhibitor (TFPI) in prostate cancer. MiR-500 expression was assessed by qRT-PCR in prostate cancer cell lines and primary tumors. Cancer patients' clinicopathological factors and overall survival were analyzed according to endogenous miR-500 level. MiR-500 was downregulated in DU145 and VCaP cells. Its effect on prostate cancer proliferation, invasion in vitro, and tumorigenicity in vivo, were probed. Possible downstream target of miR-500, TFPI was assessed by luciferase assay and qRT-PCR in prostate cancer cells. In miR-500-downregulated DU145 and VCaP cells, TFPI was silenced to see whether it was directly involved in the regulation of miR-500 in prostate cancer. TFPI alone was either upregulated or downregulated in DU145 and VCaP cells. Their effect on prostate cancer development was further evaluated. MiR-500 is upregulated in both prostate cancer cells and primary tumors. In prostate cancer patients, high miR-500 expression is associated with poor prognosis and overall survival. In DU145 and VCaP cells, miR-500 downregulation inhibited cancer proliferation, invasion in vitro, and explant growth in vivo. TFPI was verified to be associated with miR-500 in prostate cancer. Downregulation of TFPI reversed anti-cancer effects of miR-500 downregulation in prostate cancer cells. However, neither TFPI upregulation nor downregulation alone had any functional impact on prostate cancer development. MiR-500 may be a potential biomarker and molecular target in prostate cancer. TFPI may conditionally regulate prostate cancer in miR-500-downregualted prostate cancer cells. © 2017 Wiley Periodicals, Inc.

  4. Human kallikrein 11: a new biomarker of prostate and ovarian carcinoma.

    PubMed

    Diamandis, Eleftherios P; Okui, Akira; Mitsui, Shinichii; Luo, Liu-Ying; Soosaipillai, Antoninus; Grass, Linda; Nakamura, Terukazu; Howarth, David J C; Yamaguchi, Nozomi

    2002-01-01

    Human kallikrein 11 (hK11) is a putative serine protease of the human kallikrein gene family. Currently, no methods are available for measuring hK11 in biological fluids and tissues. Our aim was to develop immunological reagents and assays for measuring hK11 and examine if the concentration of this kallikrein is altered in disease states. We produced recombinant hK11 protein in a baculovirus system and used it to develop monoclonal and polyclonal antibodies against hK11. We then developed an immunofluorometric procedure for measuring hK11 in biological fluids and tissue extracts with high sensitivity and specificity. We further quantified hK11 in various biological fluids and in serum of patients with various cancers. The hK11 immunofluorometric assay is highly sensitive (detection limit, 0.1 microg/l) and specific (no detectable cross-reactivity for other homologous kallikreins). We established the tissue expression pattern of hK11 at the protein level and found the highest levels in the prostate, followed by stomach, trachea, skin, and colon. We have immunohistochemically localized hK11 in epithelial cells of various organs. We further detected hK11 in amniotic fluid, milk of lactating women, cerebrospinal fluid, follicular fluid, and breast cancer cytosols. However, highest levels were seen in prostatic tissue extracts and seminal plasma. hK11 in seminal plasma and prostatic extracts is present at approximately 300-fold lower levels than prostate-specific antigen and at approximately the same levels as hK2. hK11 expression in breast cancer cell lines is up-regulated by estradiol. Elevated serum levels of hK11 were found in 70% of women with ovarian cancer and in 60% of men with prostate cancer. This is the first reported immunological assay for hK11. Analysis of this biomarker in serum may aid in the diagnosis and monitoring of ovarian and prostatic carcinoma.

  5. Androgenic Regulation of White Adipose Tissue-Prostate Cancer Interactions

    DTIC Science & Technology

    2015-08-01

    with prostate cancer, is associated with insulin resistance, type-2 diabetes , the metabolic syndrome, and cardiovascular disease in general (Bain, 2010...initially sensitive to hormonal manipulation, and androgen-deprivation therapy (ADT) generally reverses androgen receptor (AR)– dependent growth and...hormone-insensitive population of cancer cells as a result of suppression by androgen ablation of the androgen- dependent cell population; activation of

  6. Serum tissue polypeptide antigen (TPA) and prostatic acid phosphatase (PAP) in patients with prostatic cancer.

    PubMed

    Marczyńska, A; Kulpa, J; Leńko, J; Augustyn, M

    1988-01-01

    Concurrent measurements of serum TPA and PAP concentrations by double antibody radioimmunoassays were done in 49 patients with prostatic cancer in different clinical stages. The reference group comprised patients suffering from BPH. Positive TPA was found in 32.7% of cancer patients, the lowest percentage in stage A (11.1%) and the highest in stage D (55.6%). The additional value as a diagnostic aid of the TPA test was revealed on the basis of examination of the selected group of patients with not increased PAP. Positive TPA was found in 16.7% of patients: none in stage A, 22.2% in stage B, and 33.3% in stage D. Prostatic cancer remains the most common malignancy of the genitourinary tract. The improvement in the results of treatment involves not only a modernization of treatment modalities but also the introduction of laboratory tests which give the most ample information on the stage of tumour development and improve possibilities to control tumour therapy. Besides the refinement of the determination procedures of specific prostatic markers, prostatic acid phosphatase (PAP), through radio- and enzyme-immunological methods, there is a search for additional markers which might be helpful in diagnosis and follow-up of treatment.

  7. Stiffness of benign and malignant prostate tissue measured by shear-wave elastography: a preliminary study.

    PubMed

    Rouvière, Olivier; Melodelima, Christelle; Hoang Dinh, Au; Bratan, Flavie; Pagnoux, Gaele; Sanzalone, Thomas; Crouzet, Sébastien; Colombel, Marc; Mège-Lechevallier, Florence; Souchon, Rémi

    2017-05-01

    To measure benign and malignant prostate tissue stiffness using shear-wave elastography (SWE). Thirty consecutive patients underwent transrectal SWE in the axial and sagittal planes before prostatectomy. After reviewing prostatectomy specimens, two radiologists measured stiffness in regions corresponding to cancers, lateral and median benign peripheral zone (PZ) and benign transition zone (TZ). Cancers were stiffer than benign PZ and TZ. All tissue classes were stiffer on sagittal than on axial imaging, in TZ than in PZ, and in median PZ than in lateral PZ. At multivariate analysis, the nature of tissue (benign or malignant; P < 0.00001), the imaging plane (axial or sagittal; P < 0.00001) and the location within the prostate (TZ, median PZ or lateral PZ; P = 0.0065) significantly and independently influenced tissue stiffness. On axial images, the thresholds maximising the Youden index in TZ, lateral PZ and median PZ were respectively 62 kPa, 33 kPa and 49 kPa. On sagittal images, the thresholds were 76 kPa, 50 kPa and 72 kPa, respectively. SWE can distinguish prostate malignant and benign tissues. Tissue stiffness is influenced by the imaging plane and the location within the gland. • Prostate cancers were stiffer than the benign peripheral zone • All tissue classes were stiffer on sagittal than on axial imaging • All tissue classes were stiffer in the transition zone than in the peripheral zone • All tissue classes were stiffer in the median than in the lateral peripheral zone • Taking into account imaging plane and zonal anatomy can improve cancer detection.

  8. Tookad-mediated photodynamic effects on the prostate and its adjacent tissues: in vivo study in canine models

    NASA Astrophysics Data System (ADS)

    Huang, Zheng; Chen, Qun; Luck, David; Beckers, Jill; Blanc, Dominique; Hetzel, Fred W.

    2005-04-01

    Photodynamic therapy (PDT) mediated with a vascular acting photosensitizer Tookad (pd-bacteriopheophorbide), was investigated as an alternative treatment modality for prostate cancer. Tookad photodynamic effects on the prostate and its adjacent tissues were evaluated in canine models. Interstitial prostate PDT was performed by irradiating individual lobes with a diode laser (763 nm) and 1-cm cylindrical diffuser fibers at various light doses to activate the IV administered photosensitizer Tookad (1 - 2 mg/kg). The sensitivity of the adjacent tissues to Tookad-PDT was determined by superficially irradiating the surfaces of the bladder, colon, abdominal muscle and pelvic plexus with a microlens fiber at various drug/light doses. PDT effect on the prostatic urethra was evaluated by transurethral irradiation. The prostate and adjacent tissues were harvested one-week after the treatment and subjected to histopathologic examination. At one-week post interstitial prostate PDT, the animals recovered well with little or no urethral complications. PDT induced prostate lesions were characterized by marked hemorrhagic necrosis. The bladder, colon, abdominal muscle and pelvic plexus, appeared to also be sensitive to Tookad-PDT at light dose levels greater than 40 Jcm2. Urethral mucosa appeared less sensitive to Tookad-PDT. In conclusion, Tookad-mediated PDT demonstrates very strong vascular effects and can provide an effective alternative for the treatment of localized prostate cancer. Protection of the adjacent tissues should be taken into consideration in the total prostate ablation process due to their sensitivity to the Tookad-mediated PDT.

  9. Tissue composition and density impact on the clinical parameters for (125)I prostate implants dosimetry.

    PubMed

    Oliveira, Susana Maria; Teixeira, Nuno José; Fernandes, Lisete; Teles, Pedro; Vieira, Guy; Vaz, Pedro

    2014-11-01

    The MCNPX code was used to calculate the TG-43U1 recommended parameters in water and prostate tissue in order to quantify the dosimetric impact in 30 patients treated with (125)I prostate implants when replacing the TG-43U1 formalism parameters calculated in water by a prostate-like medium in the planning system (PS) and to evaluate the uncertainties associated with Monte Carlo (MC) calculations. The prostate density was obtained from the CT of 100 patients with prostate cancer. The deviations between our results for water and the TG-43U1 consensus dataset values were -2.6% for prostate V100, -13.0% for V150, and -5.8% for D90; -2.0% for rectum V100, and -5.1% for D0.1; -5.0% for urethra D10, and -5.1% for D30. The same differences between our water and prostate results were all under 0.3%. Uncertainties estimations were up to 2.9% for the gL(r) function, 13.4% for the F(r,θ) function and 7.0% for Λ, mainly due to seed geometry uncertainties. Uncertainties in extracting the TG-43U1 parameters in the MC simulations as well as in the literature comparison are of the same order of magnitude as the differences between dose distributions computed for water and prostate-like medium. The selection of the parameters for the PS should be done carefully, as it may considerably affect the dose distributions. The seeds internal geometry uncertainties are a major limiting factor in the MC parameters deduction. Copyright © 2014. Published by Elsevier Ltd.

  10. Tissue mimicking materials for the detection of prostate cancer using shear wave elastography: A validation study

    PubMed Central

    Cao, Rui; Huang, Zhihong; Varghese, Tomy; Nabi, Ghulam

    2013-01-01

    Purpose: Quantification of stiffness changes may provide important diagnostic information and aid in the early detection of cancers. Shear wave elastography is an imaging technique that assesses tissue stiffness using acoustic radiation force as an alternate to manual palpation reported previously with quasistatic elastography. In this study, the elastic properties of tissue mimicking materials, including agar, polyacrylamide (PAA), and silicone, are evaluated with an objective to determine material characteristics which resemble normal and cancerous prostate tissue. Methods: Acoustic properties and stiffness of tissue mimicking phantoms were measured using compressional mechanical testing and shear wave elastography using supersonic shear imaging. The latter is based on the principles of shear waves generated using acoustic radiation force. The evaluation included tissue mimicking materials (TMMs) within the prostate at different positions and sizes that could mimic cancerous and normal prostate tissue. Patient data on normal and prostate cancer tissues quantified using biopsy histopathology were used to validate the findings. Pathologist reports on histopathology were blinded to mechanical testing and elastographic findings. Results: Young's modulus values of 86.2 ± 4.5 and 271.5 ± 25.7 kPa were obtained for PAA mixed with 2% Al2O3 particles and silicone, respectively. Young's modulus of TMMs from mechanical compression testing showed a clear trend of increasing stiffness with an increasing percentage of agar. The silicone material had higher stiffness values when compared with PAA with Al2O3. The mean Young's modulus value in cancerous tissue was 90.5 ± 4.5 kPa as compared to 93.8 ± 4.4 and 86.2 ± 4.5 kPa obtained with PAA with 2% Al2O3 phantom at a depth of 52.4 and 36.6 mm, respectively. Conclusions: PAA mixed with Al2O3 provides the most suitable tissue mimicking material for prostate cancer tumor material, while agar could form the surrounding

  11. Deep RNA sequencing analysis of readthrough gene fusions in human prostate adenocarcinoma and reference samples

    PubMed Central

    2011-01-01

    Background Readthrough fusions across adjacent genes in the genome, or transcription-induced chimeras (TICs), have been estimated using expressed sequence tag (EST) libraries to involve 4-6% of all genes. Deep transcriptional sequencing (RNA-Seq) now makes it possible to study the occurrence and expression levels of TICs in individual samples across the genome. Methods We performed single-end RNA-Seq on three human prostate adenocarcinoma samples and their corresponding normal tissues, as well as brain and universal reference samples. We developed two bioinformatics methods to specifically identify TIC events: a targeted alignment method using artificial exon-exon junctions within 200,000 bp from adjacent genes, and genomic alignment allowing splicing within individual reads. We performed further experimental verification and characterization of selected TIC and fusion events using quantitative RT-PCR and comparative genomic hybridization microarrays. Results Targeted alignment against artificial exon-exon junctions yielded 339 distinct TIC events, including 32 gene pairs with multiple isoforms. The false discovery rate was estimated to be 1.5%. Spliced alignment to the genome was less sensitive, finding only 18% of those found by targeted alignment in 33-nt reads and 59% of those in 50-nt reads. However, spliced alignment revealed 30 cases of TICs with intervening exons, in addition to distant inversions, scrambled genes, and translocations. Our findings increase the catalog of observed TIC gene pairs by 66%. We verified 6 of 6 predicted TICs in all prostate samples, and 2 of 5 predicted novel distant gene fusions, both private events among 54 prostate tumor samples tested. Expression of TICs correlates with that of the upstream gene, which can explain the prostate-specific pattern of some TIC events and the restriction of the SLC45A3-ELK4 e4-e2 TIC to ERG-negative prostate samples, as confirmed in 20 matched prostate tumor and normal samples and 9 lung cancer

  12. Genetic and least squares algorithms for estimating spectral EIS parameters of prostatic tissues.

    PubMed

    Halter, Ryan J; Hartov, Alex; Paulsen, Keith D; Schned, Alan; Heaney, John

    2008-06-01

    We employed electrical impedance spectroscopy (EIS) to evaluate the electrical properties of prostatic tissues. We collected freshly excised prostates from 23 men immediately following radical prostatectomy. The prostates were sectioned into 3 mm slices and electrical property measurements of complex resistivity were recorded from each of the slices using an impedance probe over the frequency range of 100 Hz to 100 kHz. The area probed was marked so that following tissue fixation and slide preparation, histological assessment could be correlated directly with the recorded EIS spectra. Prostate cancer (CaP), benign prostatic hyperplasia (BPH), non-hyperplastic glandular tissue and stroma were the primary prostatic tissue types probed. Genetic and least squares parameter estimation algorithms were implemented for fitting a Cole-type resistivity model to the measured data. The four multi-frequency-based spectral parameters defining the recorded spectrum (rho(infinity), Deltarho, f(c) and alpha) were determined using these algorithms and statistically analyzed with respect to the tissue type. Both algorithms fit the measured data well, with the least squares algorithm having a better average goodness of fit (95.2 mOmega m versus 109.8 mOmega m) and a faster execution time (80.9 ms versus 13 637 ms) than the genetic algorithm. The mean parameters, from all tissue samples, estimated using the genetic algorithm ranged from 4.44 to 5.55 Omega m, 2.42 to 7.14 Omega m, 3.26 to 6.07 kHz and 0.565 to 0.654 for rho(infinity), Deltarho, f(c) and alpha, respectively. These same parameters estimated using the least squares algorithm ranged from 4.58 to 5.79 Omega m, 2.18 to 6.98 Omega m, 2.97 to 5.06 kHz and 0.621 to 0.742 for rho(infinity), Deltarho, f(c) and alpha, respectively. The ranges of these parameters were similar to those reported in the literature. Further, significant differences (p < 0.01) were observed between CaP and BPH for the spectral parameters Deltarho and f

  13. Virus, Oncolytic virus and Human Prostate Cancer.

    PubMed

    Liu, Guang Bin; Zhao, Liang; Zhang, Lifang; Zhao, Kong-Nan

    2016-12-15

    Prostate cancer (PCa), a disease, is characterized by abnormal cell growth in the prostate - a gland in the male reproductive system. PCa is one of the leading causes of cancer death among men of all races. Although older age and a family history of the disease have been recognized as the risk factors of PCa, the cause of this cancer remains unclear. Mounting evidence suggests that infections with various viruses are causally linked to PCa pathogenesis. Published studies have provided strong evidence that at least two viruses (RXMV and HPV) contribute to prostate tumourigenicity and impact on the survival of patients with malignant PCa. Traditional therapies including chemotherapy and radiotherapy are unable to distinguish cancer cells from normal cells, which are a significant drawback and leads to toxicities for PCa patients undergoing treatment. So far, few other options are available for treating patients with advanced PCa. Virotherapy is being developed to be a novel therapy for cancers, which uses oncotropic and oncolytic viruses with their abilities to find and destroy malignant cells in the body. For PCa treatment, oncolytic virotherapy appears to be much more attractive, which uses live viruses to selectively kill cancer cells. Oncolytic viruses can be genetically engineered to induce cancer cell lysis through virus replication and expression of cytotoxic proteins. As oncolytic viruses are a relatively new class of anti-cancer immunotherapy agents, several important barriers still exist on the road to the use of oncolytic viruses for PCa therapy. In this review, we first discuss the controversy of the contribution of virus infection to PCa, and subsequently summarize the development of oncolytic virotherapy for PCa in the past several years.

  14. Telomerase-immortalized non-malignant human prostate epithelial cells retain the properties of multipotent stem cells

    SciTech Connect

    Li Hongzhen; Zhou Jianjun; Miki, Jun; Furusato, Bungo; Gu Yongpeng; Srivastava, Shiv; McLeod, David G.; Vogel, Jonathan C.; Rhim, Johng S.

    2008-01-01

    Understanding prostate stem cells may provide insight into the origin of prostate cancer. Primary cells have been cultured from human prostate tissue but they usually survive only 15-20 population doublings before undergoing senescence. We report here that RC-170N/h/clone 7 cells, a clonal cell line from hTERT-immortalized primary non-malignant tissue-derived human prostate epithelial cell line (RC170N/h), retain multipotent stem cell properties. The RC-170N/h/clone 7 cells expressed a human embryonic stem cell marker, Oct-4, and potential prostate epithelial stem cell markers, CD133, integrin {alpha}2{beta}1{sup hi} and CD44. The RC-170N/h/clone 7 cells proliferated in KGM and Dulbecco's Modified Eagle Medium with 10% fetal bovine serum and 5 {mu}g/ml insulin (DMEM + 10% FBS + Ins.) medium, and differentiated into epithelial stem cells that expressed epithelial cell markers, including CK5/14, CD44, p63 and cytokeratin 18 (CK18); as well as the mesenchymal cell markers, vimentin, desmin; the neuron and neuroendocrine cell marker, chromogranin A. Furthermore the RC170 N/h/clone 7 cells differentiated into multi tissues when transplanted into the sub-renal capsule and subcutaneously of NOD-SCID mice. The results indicate that RC170N/h/clone 7 cells retain the properties of multipotent stem cells and will be useful as a novel cell model for studying the mechanisms of human prostate stem cell differentiation and transformation.

  15. Biological effect of human serum collected before and after oral intake of Pygeum africanum on various benign prostate cell cultures

    PubMed Central

    Larré, Stéphane; Camparo, Philippe; Comperat, Eva; Boulbés, Delphine; Haddoum, Mohammed; Baulande, Sylvain; Soularue, Pascal; Costa, Pierre; Cussenot, Olivier

    2012-01-01

    Pygeum africanum (Tadenan) is a popular phytotherapeutic agent used in the treatment of symptomatic benign prostatic hyperplasia. The active compounds of the drug have not been identified, and determining the plasma concentration of the drug is, therefore, not possible. Because there are conflicting results on the efficacy of this drug, we aimed to investigate its effect on prostate cell growth in vitro using human serum collected before and after Pygeum africanum intake. We used primary and organotypic cultures of human prostatic stromal myofibroblast cell line WPMY and prostatic epithelial cell line PNT2. We also used fresh benign prostatic tissue. The serum of a treated man induced decreases in the proliferation of primary cells, organotypic cells and WPMY cells but not PNT2 cells. We also analysed the effect of treated serum on the gene expression profile of WPMY cells. The transcriptome analysis revealed an upregulation of genes involved in multiple tumour suppression pathways and a downregulation of genes involved in inflammation and oxidative-stress pathways. The oral intake of Pygeum africanum resulted in serum levels of active substances that were sufficient to inhibit the proliferation of cultured myofibroblasts prostatic cells. This inhibition was associated with changes in the transcriptome. PMID:22198631

  16. Glucocorticoid receptor antagonism reverts docetaxel resistance in human prostate cancer.

    PubMed

    Kroon, Jan; Puhr, Martin; Buijs, Jeroen T; van der Horst, Geertje; Hemmer, Daniëlle M; Marijt, Koen A; Hwang, Ming S; Masood, Motasim; Grimm, Stefan; Storm, Gert; Metselaar, Josbert M; Meijer, Onno C; Culig, Zoran; van der Pluijm, Gabri

    2016-01-01

    Resistance to docetaxel is a major clinical problem in advanced prostate cancer (PCa). Although glucocorticoids (GCs) are frequently used in combination with docetaxel, it is unclear to what extent GCs and their receptor, the glucocorticoid receptor (GR), contribute to the chemotherapy resistance. In this study, we aim to elucidate the role of the GR in docetaxel-resistant PCa in order to improve the current PCa therapies. GR expression was analyzed in a tissue microarray of primary PCa specimens from chemonaive and docetaxel-treated patients, and in cultured PCa cell lines with an acquired docetaxel resistance (PC3-DR, DU145-DR, and 22Rv1-DR). We found a robust overexpression of the GR in primary PCa from docetaxel-treated patients and enhanced GR levels in cultured docetaxel-resistant human PCa cells, indicating a key role of the GR in docetaxel resistance. The capability of the GR antagonists (RU-486 and cyproterone acetate) to revert docetaxel resistance was investigated and revealed significant resensitization of docetaxel-resistant PCa cells for docetaxel treatment in a dose- and time-dependent manner, in which a complete restoration of docetaxel sensitivity was achieved in both androgen receptor (AR)-negative and AR-positive cell lines. Mechanistically, we demonstrated down-regulation of Bcl-xL and Bcl-2 upon GR antagonism, thereby defining potential treatment targets. In conclusion, we describe the involvement of the GR in the acquisition of docetaxel resistance in human PCa. Therapeutic targeting of the GR effectively resensitizes docetaxel-resistant PCa cells. These findings warrant further investigation of the clinical utility of the GR antagonists in the management of patients with advanced and docetaxel-resistant PCa.

  17. Detection of benign epithelia, prostatic intraepithelial neoplasia, and cancer regions in radical prostatectomy tissues using Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Devpura, Suneetha; Thakur, Jagdish S.; Sarkar, Fazlul H.; Sakr, Wael A.; Naik, Vaman M.; Naik, Ratna

    2010-03-01

    We have studied benign epithelia (BE), prostatic intraepithelial neoplasia (PIN), adenocarcinoma, and cancerous tissues of different Gleason scores in human prostrate bulk tissues using Raman spectroscopy. The data shows two main differences in the Raman spectral features of BE, PIN and cancerous tissues: (i) A strong variations in the peak intensities, (ii) shift in certain peak positions. In order to quantify these variations, Raman data were analyzed using chemometric methods of principal component analysis (PCA) and discriminant function analysis (DFA). The PCA and DFA clearly separated the data into three main distinct pathological groups representing BE, PIN and cancer. Similarly the analysis of different Gleason scores shows that the data can be categorized into three distinct groups representing Gleason score 6, 7, and 8. The results demonstrate that Raman spectroscopy can be used to distinguish different stages of the prostrate cancer.

  18. Identification of candidate genes for prostate cancer-risk SNPs utilizing a normal prostate tissue eQTL data set

    PubMed Central

    Thibodeau, S. N.; French, A. J.; McDonnell, S. K.; Cheville, J.; Middha, S.; Tillmans, L.; Riska, S.; Baheti, S.; Larson, M. C.; Fogarty, Z.; Zhang, Y.; Larson, N.; Nair, A.; O'Brien, D.; Wang, L.; Schaid, D J.

    2015-01-01

    Multiple studies have identified loci associated with the risk of developing prostate cancer but the associated genes are not well studied. Here we create a normal prostate tissue-specific eQTL data set and apply this data set to previously identified prostate cancer (PrCa)-risk SNPs in an effort to identify candidate target genes. The eQTL data set is constructed by the genotyping and RNA sequencing of 471 samples. We focus on 146 PrCa-risk SNPs, including all SNPs in linkage disequilibrium with each risk SNP, resulting in 100 unique risk intervals. We analyse cis-acting associations where the transcript is located within 2 Mb (±1 Mb) of the risk SNP interval. Of all SNP–gene combinations tested, 41.7% of SNPs demonstrate a significant eQTL signal after adjustment for sample histology and 14 expression principal component covariates. Of the 100 PrCa-risk intervals, 51 have a significant eQTL signal and these are associated with 88 genes. This study provides a rich resource to study biological mechanisms underlying genetic risk to PrCa. PMID:26611117

  19. Hyper-expression of PAX2 in human metastatic prostate tumors and its role as a cancer promoter in an in vitro invasion model.

    PubMed

    Ueda, Takashi; Ito, Saya; Shiraishi, Takumi; Kulkarni, Prakash; Ueno, Akihisa; Nakagawa, Hideo; Kimura, Yasunori; Hongo, Fumiya; Kamoi, Kazumi; Kawauchi, Akihiro; Miki, Tsuneharu

    2013-09-01

    Metastasis is a consequence of many biological events, during which cancer stem cells are shifted into a malignant state. Among these events, invasion of prostate cancer cells into host tissues is possible to be assessed by means of an in vitro invasion model, and is thought to be coupled to altered expression of membrane proteins. Dysregulated functions of the factors regulating organogenesis during embryogenesis are known to facilitate metastasis of many types of cancers. PAX2 (paired box 2) is a member of the PAX transcription factor family, which regulates prostatic ductal growth and branching in organogenesis of mammalian prostates. However, the role of PAX2 in prostate cancer development remains to be determined. PAX2 expression in human prostate cancers and normal prostate epithelium were examined by quantitative RT-PCR and immunohistochemistry. Matrigel invasion assay and a gene array analysis were performed using prostate cancer cell lines transfected with either control or PAX2 siRNA. In human prostate cancers, PAX2 was hyper-expressed in metastatic cancers, but was expressed at lower levels in non-metastatic cancers. Consistent with this, PAX2 knockdown repressed cell growth and invasion in a Matrigel invasion assay. Gene ontology analysis revealed that many cell membrane proteins were downregulated after PAX2 knockdown. Our data suggested that PAX2 hyper-expression promotes the development of the metastatic state in prostate cancer cells, presumably through upregulating the expression of cell membrane proteins. Copyright © 2013 Wiley Periodicals, Inc.

  20. Alternative splicing of PSP94 (prostatic secretory protein of 94 amino acids) mRNA in prostate tissue.

    PubMed

    Xuan, J W; Chin, J L; Guo, Y; Chambers, A F; Finkelman, M A; Clarke, M W

    1995-09-21

    While performing reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of total mRNA from prostate cancer specimens, two forms of PSP94 cDNA were detected. RT-PCR products were analysed by Southern blotting and probing with exon-specific oligonucleotides. In the short form of PSP94 mRNA, designated as PSP57, exon III was found to be deleted. The two mRNA forms were confirmed by cloning and sequencing of the RT-PCR products and were found to result from alternative splicing. The alternatively spliced form, PSP57, was characterized by sequence analysis. PSP94 and PSP57 possess identical exons I and II, including identical secretion signal peptide and the 5' untranslated sequences. PSP57 has a frame-shifted exon IV and encodes a putative 57 amino acid protein with a novel, highly basic C-terminus of 41 amino acids. PSP57 mRNA was detected in other urogenital tissues (kidney, bladder) and in most tumor cell lines tested, but was not detectable in other tissues such as breast and lung. In prostate tumor cell lines, PSP57 mRNA was aberrantly spliced and localized in the nuclear fraction of the cell. Our results suggest the possible existence of a novel PSP protein that originates from alternative splicing of PSP94 mRNA in urogenital tissues.

  1. Identification of Prognostic Molecular Features in the Reactive Stroma of Human Breast and Prostate Cancer

    PubMed Central

    Provero, Paolo; Fusco, Carlo; Delorenzi, Mauro; Stehle, Jean-Christophe; Stamenkovic, Ivan

    2011-01-01

    Primary tumor growth induces host tissue responses that are believed to support and promote tumor progression. Identification of the molecular characteristics of the tumor microenvironment and elucidation of its crosstalk with tumor cells may therefore be crucial for improving our understanding of the processes implicated in cancer progression, identifying potential therapeutic targets, and uncovering stromal gene expression signatures that may predict clinical outcome. A key issue to resolve, therefore, is whether the stromal response to tumor growth is largely a generic phenomenon, irrespective of the tumor type or whether the response reflects tumor-specific properties. To address similarity or distinction of stromal gene expression changes during cancer progression, oligonucleotide-based Affymetrix microarray technology was used to compare the transcriptomes of laser-microdissected stromal cells derived from invasive human breast and prostate carcinoma. Invasive breast and prostate cancer-associated stroma was observed to display distinct transcriptomes, with a limited number of shared genes. Interestingly, both breast and prostate tumor-specific dysregulated stromal genes were observed to cluster breast and prostate cancer patients, respectively, into two distinct groups with statistically different clinical outcomes. By contrast, a gene signature that was common to the reactive stroma of both tumor types did not have survival predictive value. Univariate Cox analysis identified genes whose expression level was most strongly associated with patient survival. Taken together, these observations suggest that the tumor microenvironment displays distinct features according to the tumor type that provides survival-predictive value. PMID:21611158

  2. Identification of structural and secretory lectin-binding glycoproteins of normal and cancerous human prostate.

    PubMed

    Lad, P M; Cooper, J F; Learn, D B; Olson, C V

    1984-12-07

    We have utilized the technique of lectin-loading of SDS gels with iodinated concanavalin A and wheat germ agglutinin to identify glycoproteins in prostatic and seminal fluids as well as in prostate tissue fractions. The following subunits which bound both lectins were detected: (a) 50, 43 and 38 kDa subunits common to prostatic and seminal fluids, and an additional 55 kDa subunit which predominates only in prostatic fluid; (b) 78, 55, 50 and 43 kDa subunits in prostatic tissue cytosol and (c) 195, 170, 135, 116 and 95 kDa subunits present in the particulate fractions of prostatic tissue. Immunoblotting using specific rabbit antibodies revealed the 50 kDa band to be prostatic acid phosphatase and the 38 kDa band to be prostate-specific antigen. Interestingly, antibodies directed toward prostatic acid phosphatase were found to cross-react with the 43 kDa band. Fractionation on sucrose gradients showed that several of these particulate glycoproteins were associated with a vesicle fraction enriched in adenylate cyclase activity, implying that they are plasma membrane glycoproteins. Comparison of soluble and particulate fractions of normal and cancerous tissue homogenates was made by densitometric scanning of autoradiograms of lectin-loaded gels. Similar relative intensities of lectin-binding were obtained for corresponding proteins in normal and cancerous tissue fractions. Also, immunoblotting showed no differences in prostatic acid phosphatase or prostate-specific antigen between normal and cancerous soluble homogenate fractions. Our results suggest that major lectin-binding proteins are conserved in the transition from normal to cancerous tissue. These results may be useful in developing a multiple-marker profile of metastatic prostate cancer and for the design of imaging agents, such as monoclonal antibodies, to prominent soluble and particulate prostate glycoproteins.

  3. Modeling of intraluminal heating of biological tissue: implications for treatment of benign prostatic hyperplasia.

    PubMed

    Anvari, B; Rastegar, S; Motamedi, M

    1994-09-01

    A computer model for predicting the thermal response of a biological tissue to different intraluminal heating modalities is presented. A practical application of the model is to calculate the temperature distributions during thermal coagulation of prostate by contact heating and radiative heating. The model uses a two-dimensional axisymmetric diffusion approximation method to calculate the light distribution during radiative heating. The traditional Pennes' bio-heat equation is used to calculate the temperatures in the presence of blood flow. An implicit finite difference scheme with nonuniform grid spacings is used to solve the diffusion equation for light distribution and the bio-heat equation. Model results indicate that the radiative heating of prostate by Nd:YAG (1064 mm) and diode (810 mm) lasers can be a more effective and efficient means of coagulating a large volume of prostate, as compared to contact heating of the tissue. Blood perfusion is shown to provide a considerable heat sink as the laser exposure time is increased. Surface cooling by irrigation during the laser irradiation of tissue is shown to be an effective method for delaying tissue explosion and obtaining a large volume of coagulated tissue. The model also shows that the volume of the coagulated tissue is appreciably altered by a change in the rate of energy deposition.

  4. Simulation and experiment of soft-tissue deformation in prostate brachytherapy.

    PubMed

    Liang, Dong; Jiang, Shan; Yang, Zhiyong; Wang, Xingji

    2016-06-01

    Soft-tissue deformation is one of the major reasons for the inaccurate positioning of percutaneous needle insertion process. In this article, simulations and experiments of the needle insertion soft-tissue process are both applied to study soft-tissue deformation. A needle deflection model based on the mechanics is used to calculate the needle deflection during the interaction process. The obtained needle deflection data are applied into finite element analysis process as the system input. The uniaxial tensile strength tests, compression tests, and static indentation experiments are used to obtain the soft-tissue parameters and choose the best strain-energy function to model in the simulation. Magnetic resonance imaging is used to reconstruct the prostate, establishing both prostate three-dimensional finite element model and artificial prostate model. The needle-soft tissue interaction simulation results are compared with those of the needle insertion experiment. The displacement data of the mark point in the experiment are comparable to the simulation results. It is concluded that, using this simulation method, the surgeon can predict the deformation of the tissue and the displacement of the target in advance.

  5. Clinical validation of real-time tissue change monitoring during prostate tissue ablation with high intensity focused ultrasound.

    PubMed

    Sanghvi, Narendra T; Chen, Wo-Hsing; Carlson, Roy; Weis, Clint; Seip, Ralf; Uchida, Toyoaki; Marberger, Michael

    2017-01-01

    The purpose of these clinical studies was to validate a Tissue Change Monitoring (TCM) algorithm in vivo. TCM is a quantitative tool for the real-time assessment of HIFU dose. TCM provides quantitative analysis of the backscatter pulse echo signals (pre and immediately post HIFU) for each individual ablative site, using ultrasonic tissue characterization as a surrogate for monitoring tissue temperature. Real-time analysis generates an energy difference parameter (ΔE in dB) that is proportional to tissue temperature. Post in vitro studies, two clinical studies were conducted to validate the TCM algorithm on the Sonablate® device. Studies enrolled histologically confirmed, organ confined prostate cancer patients. The first clinical study was conducted in two phases for whole gland ablation. First eight patients' data were used to measure the algorithm performance followed by 89 additional patients for long term outcome. The second clinical study enrolled five patients; four patients with focal cancer had hemi-ablation only and one had whole gland ablation. Four 3 Fr. needles containing three thermocouples each were placed transperineally in the prostate to record tissue temperatures in the focal zone, posterior to the focal zone and on the lateral gland where no HIFU was applied. Tissue temperatures from the focal zone were correlated to the ΔE parameter. In the first clinical study, the average TCM rate was 86%. Pre and 6 months post HIFU, median PSA was 7.64 and 0.025 ng/ml respectively and 97% patients had negative biopsy. For the second clinical study, the measured prostate tissue temperatures (Average, Max, and Min) in the ablation zones were 84°, 114° and 60 °C and the corresponding ΔE (dB/10) parameters were 1.05, 2.6 and 0.4 resulting in 83% of temperatures in the range of 75°-100 °C and 17% in the 60°-74 °C range. Outside the focal zone, the average temperature was 50 °C and in the lateral lobe where no HIFU was applied, peak temperature was

  6. Tissue mimicking materials for a multi-imaging modality prostate phantom.

    PubMed

    D'Souza, W D; Madsen, E L; Unal, O; Vigen, K K; Frank, G R; Thomadsen, B R

    2001-04-01

    Materials that simultaneously mimic soft tissue in vivo for magnetic resonance imaging (MRI), ultrasound (US), and computed tomography (CT) for use in a prostate phantom have been developed. Prostate and muscle mimicking materials contain water, agarose, lipid particles, protein, Cu++, EDTA, glass beads, and thimerosal (preservative). Fat was mimicked with safflower oil suffusing a random mesh (network) of polyurethane. Phantom material properties were measured at 22 degrees C. (22 degrees C is a typical room temperature at which phantoms are used.) The values of material properties should match, as well as possible, the values for tissues at body temperature, 37 degrees C. For MRI, the primary properties of interest are T1 and T2 relaxations times, for US they are the attenuation coefficient, propagation speed, and backscatter, and for CT, the x-ray attenuation. Considering the large number of parameters to be mimicked, rather good agreement was found with actual tissue values obtained from the literature. Using published values for prostate parenchyma, T1 and T2 at 37 degrees C and 40 MHz are estimated to be about 1,100 and 98 ms, respectively. The CT number for in vivo prostate is estimated to be 45 HU (Hounsfield units). The prostate mimicking material has a T1 of 937 ms and a T2 of 88 ms at 22 degrees C and 40 MHz; the propagation speed and attenuation coefficient slope are 1,540 m/s and 0.36 dB/cm/MHz, respectively, and the CT number of tissue mimicking prostate is 43 HU. Tissue mimicking (TM) muscle differs from TM prostate in the amount of dry weight agarose, Cu++, EDTA, and the quality and quantity of glass beads. The 18 microm glass beads used in TM muscle increase US backscatter and US attenuation; the presence of the beads also has some effect on T1 but no effect on T2. The composition of tissue-mimicking materials developed is such that different versions can be placed in direct contact with one another in a phantom with no long term change in US, MRI

  7. Evaluation of prostatic optical properties and tissue response to photodynamic therapy in a canine model

    NASA Astrophysics Data System (ADS)

    Shetty, Sugandh D.; Chen, Qun; Schultz, Daniel; Wilson, Brian C.; Patterson, Michael S.; Hetzel, Fred W.; Cerny, Joseph C.

    1994-03-01

    A new modality of interstitial therapy to treat prostate cancer using photodynamic principles has been studied in a canine model. The effect of interstitial application of monochromatic light from an argon pumped dye laser at 630 nm was studied in a canine model. No significant hyperthermia was seen during the treatment. A concentric zone around the treatment fiber was seen during the treatment. A concentric zone around the treatment fiber was seen in PDT treated dogs and the maximum size was 18 mm. The data suggests that PDT may be clinically applicable in achieving tissue necrosis using interstitial light application in a solid organ like prostate.

  8. Human α(2)β(1)(HI) CD133(+VE) epithelial prostate stem cells express low levels of active androgen receptor.

    PubMed

    Williamson, Stuart C; Hepburn, Anastasia C; Wilson, Laura; Coffey, Kelly; Ryan-Munden, Claudia A; Pal, Deepali; Leung, Hing Y; Robson, Craig N; Heer, Rakesh

    2012-01-01

    Stem cells are thought to be the cell of origin in malignant transformation in many tissues, but their role in human prostate carcinogenesis continues to be debated. One of the conflicts with this model is that cancer stem cells have been described to lack androgen receptor (AR) expression, which is of established importance in prostate cancer initiation and progression. We re-examined the expression patterns of AR within adult prostate epithelial differentiation using an optimised sensitive and specific approach examining transcript, protein and AR regulated gene expression. Highly enriched populations were isolated consisting of stem (α(2)β(1)(HI) CD133(+VE)), transiently amplifying (α(2)β(1)(HI) CD133(-VE)) and terminally differentiated (α(2)β(1)(LOW) CD133(-VE)) cells. AR transcript and protein expression was confirmed in α(2)β(1)(HI) CD133(+VE) and CD133(-VE) progenitor cells. Flow cytometry confirmed that median (±SD) fraction of cells expressing AR were 77% (±6%) in α(2)β(1)(HI) CD133(+VE) stem cells and 68% (±12%) in α(2)β(1)(HI) CD133(-VE) transiently amplifying cells. However, 3-fold lower levels of total AR protein expression (peak and median immunofluorescence) were present in α(2)β(1)(HI) CD133(+VE) stem cells compared with differentiated cells. This finding was confirmed with dual immunostaining of prostate sections for AR and CD133, which again demonstrated low levels of AR within basal CD133(+VE) cells. Activity of the AR was confirmed in prostate progenitor cells by the expression of low levels of the AR regulated genes PSA, KLK2 and TMPRSS2. The confirmation of AR expression in prostate progenitor cells allows integration of the cancer stem cell theory with the established models of prostate cancer initiation based on a functional AR. Further study of specific AR functions in prostate stem and differentiated cells may highlight novel mechanisms of prostate homeostasis and insights into tumourigenesis.

  9. Castration radiosensitizes prostate cancer tissue by impairing DNA double-strand break repair.

    PubMed

    Tarish, Firas L; Schultz, Niklas; Tanoglidi, Anna; Hamberg, Hans; Letocha, Henry; Karaszi, Katalin; Hamdy, Freddie C; Granfors, Torvald; Helleday, Thomas

    2015-11-04

    Chemical castration improves responses to radiotherapy in prostate cancer, but the mechanism is unknown. We hypothesized that this radiosensitization is caused by castration-mediated down-regulation of nonhomologous end joining (NHEJ) repair of DNA double-strand breaks (DSBs). To test this, we enrolled 48 patients with localized prostate cancer in two arms of the study: either radiotherapy first or radiotherapy after neoadjuvant castration treatment. We biopsied patients at diagnosis and before and after castration and radiotherapy treatments to monitor androgen receptor, NHEJ, and DSB repair in verified cancer tissue. We show that patients receiving neoadjuvant castration treatment before radiotherapy had reduced amounts of the NHEJ protein Ku70, impaired radiotherapy-induced NHEJ activity, and higher amounts of unrepaired DSBs, measured by γ-H2AX foci in cancer tissues. This study demonstrates that chemical castration impairs NHEJ activity in prostate cancer tissue, explaining the improved response of patients with prostate cancer to radiotherapy after chemical castration. Copyright © 2015, American Association for the Advancement of Science.

  10. Interaction between high power 532nm laser and prostatic tissue: in vitro evaluation for laser prostatectomy

    NASA Astrophysics Data System (ADS)

    Kang, Hyun Wook; Peng, Yihlih Steven; Stinson, Douglas

    2011-03-01

    Photoselective vaporization of the prostate (PVP) has been developed for effective treatment of obstructive benign prostatic hyperplasia. To maximize tissue ablation for large prostate gland, identifying the optimal power level for PVP is still necessary. We investigated the effect of various power levels on in vitro bovine prostate ablation with a 532-nm laser system. A custom-made 532-nm laser was employed to provide various power levels, delivered through a newly designed 750-μm side-firing fiber. Tissue ablation efficiency was evaluated in terms of power (P; 120~200W), treatment speed of fiber (TS; 2~8 mm/s), and working distance between fiber and tissue surface (WD; 1~5 mm). Coagulation depth was also estimated macroscopically and histologically (H&E) at various Ps. Both 180 and 200W yielded comparable ablated volume (104.3+/-24.7 vs. 104.1+/-23.9 mm3 at TS=4 mm/s and WD=2 mm; p=0.99); thus, 180W was identified as the optimal power to maximize tissue ablation, by removing tissue up to 80% faster than 120W (41.7+/-9.9 vs. 23.2+/-3.4 mm3/s at TS=4 mm/s and WD=2 mm; p<0.005). Tissue ablation was maximized at TS=4 mm/s and ablated equally efficiently at up to 3 mm WD (104.5+/-16.7 mm3 for WD=1 mm vs. 93.4+/-7.4 mm3 for WD=3 mm at 180W; p=0.33). The mean thickness of coagulation zone for 180W was 20% thicker than that for 120W (1.31+/-0.17 vs. 1.09+/-0.16 mm; p<0.005). The current in vitro study demonstrated that 180W was the optimal power to maximize tissue ablation efficiency with enhanced coagulation characteristics.

  11. Distribution of adenosine deaminase complexing protein (ADCP) in human tissues.

    PubMed

    Dinjens, W N; ten Kate, J; van der Linden, E P; Wijnen, J T; Khan, P M; Bosman, F T

    1989-12-01

    The normal distribution of adenosine deaminase complexing protein (ADCP) in the human body was investigated quantitatively by ADCP-specific radioimmunoassay (RIA) and qualitatively by immunohistochemistry. In these studies we used a specific rabbit anti-human ADCP antiserum. In all 19 investigated tissues, except erythrocytes, ADCP was found by RIA in the soluble and membrane fractions. From all tissues the membrane fractions contained more ADCP (expressed per mg protein) than the soluble fractions. High membrane ADCP concentrations were found in skin, renal cortex, gastrointestinal tract, and prostate. Immunoperoxidase staining confirmed the predominant membrane-associated localization of the protein. In serous sweat glands, convoluted tubules of renal cortex, bile canaliculi, gastrointestinal tract, lung, pancreas, prostate gland, salivary gland, gallbladder, mammary gland, and uterus, ADCP immunoreactivity was found confined to the luminal membranes of the epithelial cells. These data demonstrate that ADCP is present predominantly in exocrine glands and absorptive epithelia. The localization of ADCP at the secretory or absorptive apex of the cells suggests that the function of ADCP is related to the secretory and/or absorptive process.

  12. Absence of XMRV and closely related viruses in primary prostate cancer tissues used to derive the XMRV-infected cell line 22Rv1.

    PubMed

    Das Gupta, Jaydip; Luk, Ka-Cheung; Tang, Ning; Gaughan, Christina; Klein, Eric A; Kandel, Eugene S; Hackett, John; Silverman, Robert H

    2012-01-01

    The 22Rv1 cell line is widely used for prostate cancer research and other studies throughout the world. These cells were established from a human prostate tumor, CWR22, that was serially passaged in nude mice and selected for androgen independence. The 22Rv1 cells are known to produce high titers of xenotropic murine leukemia virus-related virus (XMRV). Recent studies suggested that XMRV was inadvertently created in the 1990's when two murine leukemia virus (MLV) genomes (pre-XMRV1 and pre-XMRV-2) recombined during passaging of the CWR22 tumor in mice. The conclusion that XMRV originated from mice and not the patient was based partly on the failure to detect XMRV in early CWR22 xenografts. While that deduction is certainly justified, we examined the possibility that a closely related virus could have been present in primary tumor tissue. Here we report that we have located the original prostate tumor tissue excised from patient CWR22 and have assayed the corresponding DNA by PCR and the tissue sections by fluorescence in situ hybridization for the presence of XMRV or a similar virus. The primary tumor tissues lacked mouse DNA as determined by PCR for intracisternal A type particle DNA, thus avoiding one of the limitations of studying xenografts. We show that neither XMRV nor a closely related virus was present in primary prostate tissue of patient CWR22. Our findings confirm and reinforce the conclusion that XMRV is a recombinant laboratory-generated mouse virus that is highly adapted for human prostate cancer cells.

  13. Magnetic resonance spectroscopy: A promising tool for the diagnostics of human prostate cancer?☆

    PubMed Central

    Kurth, Johannes; DeFeo, Elita; Cheng, Leo L.

    2013-01-01

    Background Prostate Cancer (CaP) is one of the topmost diagnosed malignant diseases worldwide. In developed countries, early cancer detection methods have led to an increase of incidence rates over the last decades; however, with great variance of the prognosis. There is no diagnostic tool for an exact prediction of tumor aggressiveness, thus there is a lack of adequate and optimal treatment planning. Methods Electronic databases (Medline, PubMed) were scanned for scientific literature. Basic concepts of magnetic resonance spectroscopy (MRS), important results and its clinical applications were extracted and reviewed in this article. Conclusions MRS provides crucial information about the metabolic status of human prostate samples while preserving the specimens for further investigations. Single metabolites and metabolomic profiles can be quantified to distinguish benign from malignant tissue and to predict aggressiveness, such as the recurrence rates of CaP. Studies are also anticipating that MRS might be beneficially applicable for in vivo investigations in the future. PMID:21930088

  14. Androgen Receptor Variants and Prostate Cancer in Humanized AR Mice

    PubMed Central

    Albertelli, Megan A.; O’Mahony, Orla A.

    2008-01-01

    SUMMARY Androgen, acting via the androgen receptor (AR), is central to male development, differentiation and hormone-dependent diseases such as prostate cancer. AR is actively involved in the initiation of prostate cancer, the transition to androgen independence, and many mechanisms of resistance to therapy. To examine genetic variation of AR in cancer, we created mice by germ-line gene targeting in which human AR sequence replaces that of the mouse. Since shorter length of a polymorphic N-terminal glutamine (Q) tract has been linked to prostate cancer risk, we introduced alleles with 12, 21 or 48 Qs to test this association. The three “humanized” AR mouse strains (h/mAR) are normal physiologically, as well as by cellular and molecular criteria, although slight differences are detected in AR target gene expression, correlating inversely with Q tract length. However, distinct allele-dependent differences in tumorigenesis are evident when these mice are crossed to a transgenic prostate cancer model. Remarkably, Q tract variation also differentially impacts disease progression following androgen depletion. This finding emphasizes the importance of AR function in androgen-independent as well as –dependent disease. These mice provide a novel genetic paradigm in which to dissect opposing functions of AR in tumor suppression vs. oncogenesis. PMID:17936615

  15. Neuroendocrine Transdifferentiation in Human Prostate Cancer Cells: An Integrated Approach.

    PubMed

    Cerasuolo, Marianna; Paris, Debora; Iannotti, Fabio A; Melck, Dominique; Verde, Roberta; Mazzarella, Enrico; Motta, Andrea; Ligresti, Alessia

    2015-08-01

    Prostate cancer is highly sensitive to hormone therapy because androgens are essential for prostate cancer cell growth. However, with the nearly invariable progression of this disease to androgen independence, endocrine therapy ultimately fails to control prostate cancer in most patients. Androgen-independent acquisition may involve neuroendocrine transdifferentiation, but there is little knowledge about this process, which is presently controversial. In this study, we investigated this question in a novel model of human androgen-dependent LNCaP cells cultured for long periods in hormone-deprived conditions. Strikingly, characterization of the neuroendocrine phenotype by transcriptomic, metabolomic, and other statistically integrated analyses showed how hormone-deprived LNCaP cells could transdifferentiate to a nonmalignantneuroendocrine phenotype. Notably, conditioned media from neuroendocrine-like cells affected LNCaP cell proliferation. Predictive in silico models illustrated how after an initial period, when LNCaP cell survival was compromised by an arising population of neuroendocrine-like cells, a sudden trend reversal occurred in which the neuroendocrine-like cells functioned to sustain the remaining androgen-dependent LNCaP cells. Our findings provide direct biologic and molecular support for the concept that neuroendocrine transdifferentiation in prostate cancer cell populations influences the progression to androgen independence.

  16. Can color doppler predict the uniformity of HIFU-induced prostate tissue destruction?

    PubMed

    Rouvière, Olivier; Curiel, Laura; Chapelon, Jean-Yves; Bouvier, Raymonde; Ecochard, René; Gelet, Albert; Lyonnet, Denis

    2004-09-01

    Tissue blood perfusion influences the results of some hyperthermia and thermotherapy procedures, but its role in the outcome of prostate cancer treatment by high-intensity focused ultrasound (HIFU) has not been evaluated yet. We evaluated preoperative prostate color Doppler as a predictor of the efficacy of HIFU treatment. Thirty-five patients underwent pre- and post-contrast color Doppler examination of the prostate before HIFU treatment. Specific software was used to calculate, on color Doppler images, the color pixel density (CPD), and the specific flow (SF, i.e., mean velocity x CPD) in different regions of interest. Post-treatment sextant biopsies were obtained in 31 patients, 5.8 +/- 2.8 months after HIFU treatment. No significant correlation was found between the uniformity of HIFU-induced tissue destruction observed on control biopsies and the pre-treatment CPD/SF values in any region of interest, either before or after contrast injection. On the other hand, history of radiation therapy was significantly associated with homogeneous tissue destruction and history of hormone therapy was significantly associated with incomplete tissue destruction. Color Doppler cannot predict the uniformity of HIFU-induced tissue destruction. History of radiation therapy was found to be a factor of favorable prognosis and history of hormone therapy was found to be a factor of poor prognosis in our population.

  17. Exome enrichment and SOLiD sequencing of formalin fixed paraffin embedded (FFPE) prostate cancer tissue.

    PubMed

    Menon, Roopika; Deng, Mario; Boehm, Diana; Braun, Martin; Fend, Falko; Boehm, Detlef; Biskup, Saskia; Perner, Sven

    2012-01-01

    Next generation sequencing (NGS) technologies have revolutionized cancer research allowing the comprehensive study of cancer using high throughput deep sequencing methodologies. These methods detect genomic alterations, nucleotide substitutions, insertions, deletions and copy number alterations. SOLiD (Sequencing by Oligonucleotide Ligation and Detection, Life Technologies) is a promising technology generating billions of 50 bp sequencing reads. This robust technique, successfully applied in gene identification, might be helpful in detecting novel genes associated with cancer initiation and progression using formalin fixed paraffin embedded (FFPE) tissue. This study's aim was to compare the validity of whole exome sequencing of fresh-frozen vs. FFPE tumor tissue by normalization to normal prostatic FFPE tissue, obtained from the same patient. One primary fresh-frozen sample, corresponding FFPE prostate cancer sample and matched adjacent normal prostatic tissue was subjected to exome sequencing. The sequenced reads were mapped and compared. Our study was the first to show comparable exome sequencing results between FFPE and corresponding fresh-frozen cancer tissues using SOLiD sequencing. A prior study has been conducted comparing the validity of sequencing of FFPE vs. fresh frozen samples using other NGS platforms. Our validation further proves that FFPE material is a reliable source of material for whole exome sequencing.

  18. Exome Enrichment and SOLiD Sequencing of Formalin Fixed Paraffin Embedded (FFPE) Prostate Cancer Tissue

    PubMed Central

    Menon, Roopika; Deng, Mario; Boehm, Diana; Braun, Martin; Fend, Falko; Boehm, Detlef; Biskup, Saskia; Perner, Sven

    2012-01-01

    Next generation sequencing (NGS) technologies have revolutionized cancer research allowing the comprehensive study of cancer using high throughput deep sequencing methodologies. These methods detect genomic alterations, nucleotide substitutions, insertions, deletions and copy number alterations. SOLiD (Sequencing by Oligonucleotide Ligation and Detection, Life Technologies) is a promising technology generating billions of 50 bp sequencing reads. This robust technique, successfully applied in gene identification, might be helpful in detecting novel genes associated with cancer initiation and progression using formalin fixed paraffin embedded (FFPE) tissue. This study’s aim was to compare the validity of whole exome sequencing of fresh-frozen vs. FFPE tumor tissue by normalization to normal prostatic FFPE tissue, obtained from the same patient. One primary fresh-frozen sample, corresponding FFPE prostate cancer sample and matched adjacent normal prostatic tissue was subjected to exome sequencing. The sequenced reads were mapped and compared. Our study was the first to show comparable exome sequencing results between FFPE and corresponding fresh-frozen cancer tissues using SOLiD sequencing. A prior study has been conducted comparing the validity of sequencing of FFPE vs. fresh frozen samples using other NGS platforms. Our validation further proves that FFPE material is a reliable source of material for whole exome sequencing. PMID:22942743

  19. Collecting and Studying Blood and Tissue Samples From Patients With Locally Recurrent or Metastatic Prostate or Bladder/Urothelial Cancer

    ClinicalTrials.gov

    2016-12-06

    Healthy Control; Localized Urothelial Carcinoma of the Renal Pelvis and Ureter; Metastatic Malignant Neoplasm in the Bone; Metastatic Malignant Neoplasm in the Soft Tissues; Metastatic Urothelial Carcinoma of the Renal Pelvis and Ureter; Recurrent Bladder Carcinoma; Recurrent Prostate Carcinoma; Recurrent Urothelial Carcinoma of the Renal Pelvis and Ureter; Stage IV Bladder Cancer; Stage IV Bladder Urothelial Carcinoma; Stage IV Prostate Cancer

  20. Expression and significance of S100P, CD147, and OCT4 in different prostate cancer tissue TNM stages.

    PubMed

    Wang, Q; Zhang, J G; Wang, W

    2015-06-18

    The aim of this project was to investigate the expression and significance of S100P, CD147, and OCT4 in prostate cancer tissue at different TNM stages. We enrolled 54 patients with prostate cancer, 40 with benign prostatic hyperplasia, and 20 subjects with normal prostates. S100P, CD147, and OCT4 were detected by immunohistochemistry. The positive rate of S100P detection was 18.52% in prostate cancer tissues, significantly lower than in normal and benign prostate hyperplasia tissues (P ˂ 0.05). The positive expression rate of CD147 and OCT4 were 100 and 77.38% in prostate cancer tissue, respectively, both markedly higher than in normal and benign prostate hyperplasia tissue (P ˂ 0.05). The positive rate of S100P in stage V was 0, which was significantly lower than in stages I (37.50%) and II (35.71%) (P ˂ 0.05). OCT4 expression in stages III (86.67%) and V (94.12%) was higher than in stage I (37.50%). The positive rate of S100P in patients with distant metastasis was 4%, which was significantly lower than that in patients without metastases (P ˂ 0.05). In contrast, the positive rate of OCT4 in patients with distant metastasis was 92%. S100P, CD147, and OCT4 expression in prostate cancer patients with different degrees of differentiation had no significant difference (P > 0.05). Overall, our results demonstrated that S100P expression in prostate cancer tissue was significantly decreased, whereas CD147 and OCT4 expression was increased. Their expression levels were closely associated with TNM stage and distant metastasis, but were not related to the degree of differentiation.

  1. A model for the design and construction of a resource for the validation of prognostic prostate cancer biomarkers: the Canary Prostate Cancer Tissue Microarray

    PubMed Central

    Hawley, Sarah; Fazli, Ladan; McKenney, Jesse K.; Simko, Jeff; Troyer, Dean; Nicolas, Marlo; Newcomb, Lisa F.; Cowan, Janet E.; Crouch, Luis; Ferrari, Michelle; Hernandez, Javier; Hurtado-Coll, Antonio; Kuchinsky, Kyle; Liew, Janet; Mendez-Meza, Rosario; Smith, Elizabeth; Tenggara, Imelda; Zhang, Xiaotun; Carroll, Peter R.; Chan, June M.; Gleave, Martin; Lance, Raymond; Lin, Daniel W.; Nelson, Peter S.; Thompson, Ian M.; Feng, Ziding; True, Lawrence D.; Brooks, James D.

    2012-01-01

    Tissue microarrays provide unique resources for rapid evaluation and validation of tissue biomarkers. The Canary Foundation Retrospective Prostate Tissue Microarray Resource used a rigorous statistical design, quota sampling, a variation of the case-cohort study, to select patients for inclusion in a multicenter, retrospective prostate cancer tissue microarray cohort. The study is designed to definitively validate tissue biomarkers of prostate cancer recurrence after radical prostatectomy. Tissue samples from over 1,000 participants treated for prostate cancer with radical prostatectomy between 1995 and 2004 were selected at six participating institutions in the United States and Canada. This design captured the heterogeneity of screening and clinical practices in the contemporary North American population. Standardized clinical data were collected in a centralized database. The project has been informative in several respects. The scale and complexity of assembling tissue microarrays (TMAs) with over 200 cases at each of six sites involved unanticipated levels of effort and time. Our statistical design promises to provide a model for outcome-based studies where tissue localization methods are applied to high-density tissue microarrays. PMID:23232570

  2. Hypothermia and rewarming induce gene expression and multiplication of cells in healthy rat prostate tissue.

    PubMed

    Kaija, Helena; Pakanen, Lasse; Kortelainen, Marja-Leena; Porvari, Katja

    2015-01-01

    Prostate cancer has been extensively studied, but cellular stress responses in healthy prostate tissue are rarely investigated. Hypothermia is known to cause alterations in mRNA and protein expressions and stability. The aim of this study was to use normal rat prostate as a model in order to find out consequences of cold exposure and rewarming on the expressions of genes which are either members or functionally/structurally related to erythroblastic leukemia viral oncogene B (ErbB) signaling pathway. Relative mRNA expressions of amphiregulin (AMR), cyclin D1 (CyD1), cyclin-dependent kinase inhibitor 1A (p21), transmembrane form of the prostatic acid phosphatase (PAcP), thrombomodulin (TM) and heat shock transcription factor 1 (HSF1) in rat ventral prostate were quantified in mild (2 or 4.5 h at room temperature) and severe (2 or 4.5 h at +10°C) hypothermia and in rewarming after cold exposure (2 h at +10°C followed by 2 h at room temperature or 3 h at +28°C). AMR protein level, apoptotic Bcl-2 associated X protein to B-cell CLL/lymphoma 2 (Bax/Bcl-2) mRNA ratio and proliferative index Ki-67 were determined. 4.5-h mild hypothermia, 2-h severe hypothermia and rewarming increased expression of all these genes. Elevated proliferation index Ki-67 could be seen in 2-h severe hypothermia, and the proliferation index had its highest value in longer rewarming with totally recovered normal body temperature. Pro-apoptotic tendency could be seen in 2-h mild hypothermia while anti-apoptosis was predominant in 4.5-h mild hypothermia and in shorter rewarming with only partly recovered body temperature. Hypothermia and following rewarming promote the proliferation of cells in healthy rat prostate tissue possibly via ErbB signaling pathway.

  3. Evaluation of the ERETIC method as an improved quantitative reference for 1H HR-MAS spectroscopy of prostate tissue.

    PubMed

    Albers, Mark J; Butler, Thomas N; Rahwa, Iman; Bao, Nguyen; Keshari, Kayvan R; Swanson, Mark G; Kurhanewicz, John

    2009-03-01

    The Electronic REference To access In vivo Concentrations (ERETIC) method was applied to (1)H HR-MAS spectroscopy. The accuracy, precision, and stability of ERETIC as a quantitative reference were evaluated in solution and human prostate tissue samples. For comparison, the reliability of 3-(trimethylsilyl)propionic-2,2,3,3-d(4) acid (TSP) as a quantitation reference was also evaluated. The ERETIC and TSP peak areas were found to be stable in solution over the short-term and long-term, with long-term relative standard deviations (RSDs) of 4.10% and 2.60%, respectively. Quantification of TSP in solution using the ERETIC peak as a reference and a calibrated, rotor-dependent conversion factor yielded results with a precision < or =2.9% and an accuracy error < or =4.2% when compared with the expected values. The ERETIC peak area reproducibility was superior to TSP's reproducibility, corrected for mass, in both prostate surgical and biopsy samples (4.53% vs. 21.2% and 3.34% vs. 31.8%, respectively). Furthermore, the tissue TSP peaks exhibited only 27.5% of the expected area, which would cause an overestimation of metabolite concentrations if used as a reference. The improved quantification accuracy and precision provided by ERETIC may enable the detection of smaller metabolic differences that may exist between individual tissue samples and disease states.

  4. Relationship between electrical admittivity and quantitative histopathology in human prostate

    NASA Astrophysics Data System (ADS)

    Halter, Ryan; Milone, Michael; Schned, Alan; Heaney, John

    2010-04-01

    Passive bioelectrical properties have been demonstrated to provide sufficient contrast for use in differentiating benign from malignant tissue in a number of different organs including breast, prostate, cervix, bladder, and skin. The underlying microscopic anatomy responsible for these measured differences has been primarily speculative in the past. In this study we recorded electrical conductivity and permittivity spectra (100 Hz - 100 kHz) from 464 three mm diameter circular prostate samples. Each of these tissue specimens were stained with hematoxylin and eosin, processed onto microscopy slides, and digitized using optical microscopy. We used digital imaging processing tools to extract quantitative morphological features including total number of glands, average and total glandular lumen size, shape characteristics of the luminal spaces, and average and total glandular perimeter lengths. Correlative analysis was performed to assess the relationships between the tissue architectural features and the precisely co-registered electrical properties. We report on the findings from this analysis. This statistical assessment aims to provide a valuable piece of new information to help formulate a better understanding of the precise influence morphological architecture has on the flow of current through tissue.

  5. Cytotoxic Necrotizing Factor Type 1-Positive Escherichia coli Causes Increased Inflammation and Tissue Damage to the Prostate in a Rat Prostatitis Model

    PubMed Central

    Rippere-Lampe, Karen E.; Lang, Michael; Ceri, Howard; Olson, Merle; Lockman, Hank A.; O'Brien, A. D.

    2001-01-01

    Infection of rat prostates with cytotoxic necrotizing factor type 1 (CNF1)-positive uropathogenic Escherichia coli caused more inflammation-mediated morphological and histological tissue damage than did infection with isogenic CNF1-negative mutants. These striking differences occurred despite the finding that bacterial counts for the strain pairs were indistinguishable. We conclude that CNF1 contributes to E. coli virulence in a model of acute prostatitis. To our knowledge, the results of this study provide the first demonstration of a role for any uropathogenic E. coli virulence factor in acute prostatitis. PMID:11553597

  6. First Evidence that Sika Deer (Cervus nippon) Velvet Antler Extract Suppresses Migration of Human Prostate Cancer Cells

    PubMed Central

    Tang, YuJiao; Jeon, Byong-Tae; Wang, Yanmei; Choi, Eun-Ju; Kim, Yon-Suk; Hwang, Jin-Woo; Park, Pyo-Jam; Moon, Sang Ho; Kim, Eun-Kyung

    2015-01-01

    Deer velvet antler (DVA) is one of the most popular medicines in China. Numerous studies have demonstrated that velvet antler possess biological effects. However, data regarding its anti-migration activity on prostate cancer is scarce. In this study, we investigated the inhibitory effect of top DVA (T-DVA) on the expression of prostate-specific antigen (PSA) and migration-related genes in the human prostate cancer cell, LNCaP. The T-DVA down-regulated the expression of PSA. In addition, the RadiusTM assay revealed that T-DVA inhibited the migration behavior of prostate cancer cells. Furthermore, the expression of matrix metalloproteinase (MMP)-9 and vascular endothelial growth factor (VEGF) was also decreased with T-DVA. On the contrary, T-DVA increased the tissue inhibition of metalloproteinase (TIMP)-1 and (TIMP)-2. Taken together, our findings indicate that the T-DVA possesses anti-migration activity on prostate cancer cells. This is the first study of DVA to report the anti-migration activity on prostate cancer. PMID:26761873

  7. First Evidence that Sika Deer (Cervus nippon) Velvet Antler Extract Suppresses Migration of Human Prostate Cancer Cells.

    PubMed

    Tang, YuJiao; Jeon, Byong-Tae; Wang, Yanmei; Choi, Eun-Ju; Kim, Yon-Suk; Hwang, Jin-Woo; Park, Pyo-Jam; Moon, Sang Ho; Kim, Eun-Kyung

    2015-01-01

    Deer velvet antler (DVA) is one of the most popular medicines in China. Numerous studies have demonstrated that velvet antler possess biological effects. However, data regarding its anti-migration activity on prostate cancer is scarce. In this study, we investigated the inhibitory effect of top DVA (T-DVA) on the expression of prostate-specific antigen (PSA) and migration-related genes in the human prostate cancer cell, LNCaP. The T-DVA down-regulated the expression of PSA. In addition, the Radius(TM) assay revealed that T-DVA inhibited the migration behavior of prostate cancer cells. Furthermore, the expression of matrix metalloproteinase (MMP)-9 and vascular endothelial growth factor (VEGF) was also decreased with T-DVA. On the contrary, T-DVA increased the tissue inhibition of metalloproteinase (TIMP)-1 and (TIMP)-2. Taken together, our findings indicate that the T-DVA possesses anti-migration activity on prostate cancer cells. This is the first study of DVA to report the anti-migration activity on prostate cancer.

  8. Characterization of tissue optical properties for prostate PDT using interstitial diffuse optical tomography

    NASA Astrophysics Data System (ADS)

    Liang, Xing; Wang, Ken Kang-hsin; Zhu, Timothy C.

    2012-02-01

    Photodynamic therapy (PDT) is an important treatment modality for localized diseases such as prostate cancer. In prostate PDT, light distribution is an important factor because it is directly related to treatment efficacy. During PDT, light distribution is determined by tissue optical property distributions (or heterogeneity). In this study, an interstitial diffuse optical tomography (iDOT) method was used to characterize optical properties in tissues. Optical properties (absorption and reduced scattering coefficients) of the prostate gland were reconstructed by solving the inverse problem using an adjoint model based on diffusion equation using a modified matlab public user code NIRFAST. In the modified NIRFAST method, linear sources were modeled for the reconstruction. Cross talking between absorption coefficients and reduced scattering coefficients were studied to have minimal effect, and a constrained optical property method (set either absorption coefficient or reduced scattering coefficient to be homogeneous) is also studied. A prostate phantom with optical anomalies was used to verify the iDOT method. The reconstructed results were compared with the known optical properties, and the spatial distribution of optical properties for this phantom was successfully reconstructed.

  9. Noninvasive surgery of prostate tissue by high-intensity focused ultrasound: an updated report

    NASA Astrophysics Data System (ADS)

    Sanghvi, Narendra T.; Syrus, J.; Foster, Richard S.; Bihrle, Richard; Casey, Richard W.; Uchida, Toyoak

    2000-05-01

    High Intensity Focused Ultrasound (HIFU) has been clinically used for the treatment of benign prostatic hyperplasia (BPH) and it is experimentally applied for the treatment of localized prostate caner (PC). Recent advances in the transducer material and technology have permitted to combine the ultrasound visualization capability and HIFU on the same ceramic crystal. Also, the transducer efficiency has increased to a level that a smaller size intracavity probe can be made to produce sufficient acoustic power required for the focused ultrasound surgery of the prostate. Using this technology, 4 MHz mechanically scanning transrectal ultrasound probes has been designed. The transrectal probes are used with Sonablate (SB-200, manufactured by Focus Surgery, Inc., Indianapolis, IN) device. The SB-200 produces both transverse and longitudinal images of the prostate. The transverse and longitudinal images are used for selection of tissue volume, treatment planning and monitoring of tissue during the HIFU treatment cycle. The paper reviews the present operation of the device and recent clinical protocol that has improved efficiency, efficacy and safety of the device. The two years follow-up clinical results from the multi-site US Pilot Study (USPS) and The Male Health Centre are compared with the Kitasato-study (Kitasato School of Medicine, Sagamihara, Japan).

  10. Influence of trace elements in human tissue in low-energy photon brachytherapy dosimetry

    NASA Astrophysics Data System (ADS)

    White, Shane A.; Landry, Guillaume; van Gils, Francis; Verhaegen, Frank; Reniers, Brigitte

    2012-06-01

    The aim of this paper is to determine the dosimetric impact of trace elements in human tissues for low-energy photon sources used in brachytherapy. Monte Carlo dose calculations were used to investigate the dosimetric effect of trace elements present in normal or cancerous human tissues. The effect of individual traces (atomic number Z = 11-30) was studied in soft tissue irradiated by low-energy brachytherapy sources. Three other tissue types (prostate, adipose and mammary gland) were also simulated with varying trace concentrations to quantify the contribution of each trace to the dose distribution. The dose differences between cancerous and healthy prostate tissues were calculated in single- and multi-source geometries. The presence of traces in a tissue produces a difference in the dose distribution that is dependent on Z and the concentration of the trace. Low-Z traces (Na) have a negligible effect (<0.3%) in all tissues, while higher Z (K) had a larger effect (>3%). There is a potentially significant difference in the dose distribution between cancerous and healthy prostate tissues (4%) and even larger if compared to the trace-free composition (15%) in both single- and multi-sourced geometries. Trace elements have a non-negligible (up to 8% in prostate D90) effect on the dose in tissues irradiated with low-energy photon sources. This study underlines the need for further investigation into accurate determination of the trace composition of tissues associated with low-energy brachytherapy. Alternatively, trace elements could be incorporated as a source of uncertainty in dose calculations. This work was part of an invited presentation at the ‘International Workshop on Recent Advances in Monte Carlo Techniques for Radiation Therapy’, held in Montreal, June 8-10, 2011.

  11. Characterization of normal and malignant prostate tissue by Fourier transform infrared microspectroscopy.

    PubMed

    Pezzei, Christine; Pallua, Johannes D; Schaefer, Georg; Seifarth, Christof; Huck-Pezzei, Verena; Bittner, Lukas K; Klocker, Helmut; Bartsch, Georg; Bonn, Guenther K; Huck, Christian W

    2010-11-01

    Prostate cancer has become one of the most common malignancies worldwide. Morphological and histomorphological evaluation of this disease is a well established technique for the cancer classification and has remained relatively unchanged since several decades, although it remains a time consuming and subjective technique, with unsatisfactory levels of inter- and intra-observer discrepancy. Novel approaches for histological recognition are necessary to identify and to investigate cancer in detail. Fourier transform infrared (FTIR) spectroscopic imaging has become an essential tool for the detection, identification and characterization of the molecular components of biological processes, such as those responsible for the dynamic properties of cancer progression. Major advantage of this new technique is the acquisition of local molecular expression profiles while maintaining the topographic integrity of the tissue and avoiding time-consuming extraction, purification and separation steps. By using this method it is possible to investigate the spatial distribution of proteins, lipids, carbohydrates, cholesterols, nucleic acids, phospholipids and small molecules within biological systems by in situ analysis of tissue sections. We applied this technique on prostate cancer patients radical prostatectomy specimens in order to develop new tools for histomorphological analysis and the characterization of snap frozen prostate cancer tissues. As a first step, an optimization of sample preparation, tissue section thickness and IR slide material was performed. Special preparation methods for FTIR imaging are the essential requirements to maintain the spatial arrangement of compounds and avoid delocalization and degradation of the analytes. Subsequently, selected cancer samples were characterized with the prior optimized parameters and analyzed by univariate and cluster analysis. For the interpretation and calibration of the system we correlated the FTIR-images with the

  12. Human dignity and human tissue: a meaningful ethical relationship?

    PubMed

    Kirchhoffer, David G; Dierickx, Kris

    2011-09-01

    Human dignity has long been used as a foundational principle in policy documents and ethical guidelines intended to govern various forms of biomedical research. Despite the vast amount of literature concerning human dignity and embryonic tissues, the majority of biomedical research uses non-embryonic human tissue. Therefore, this contribution addresses a notable lacuna in the literature: the relationship, if any, between human dignity and human tissue. This paper first elaborates a multidimensional understanding of human dignity that overcomes many of the shortcomings associated with the use of human dignity in other ethical debates. Second, it discusses the relationship between such an understanding of human dignity and 'non-embryonic' human tissue. Finally, it considers the implications of this relationship for biomedical research and practice involving human tissue. The contribution demonstrates that while human tissue cannot be said to have human dignity, human dignity is nevertheless implicated by human tissue, making what is done with human tissue and how it is done worthy of moral consideration.

  13. SSeCKS/AKAP12 induces repulsion between human prostate cancer and microvessel endothelial cells through the activation of Semaphorin 3F.

    PubMed

    Xie, Wen; Su, Wei; Zhang, Lijuan; Shang, Qingkun; Su, Bing

    2017-09-02

    Metastasis remains the primary cause of prostate cancer related death. Cancer cells need to contact endothelial cells and disrupt endothelial junctions to cross the endothelium for invasion and metastasis. The suppression of heterotypic repulsion between cancer and endothelial cells allows cancer cells to invade into the surrounding tissue. Here, we demonstrate that SSeCKS/AKAP12 induced repulsion between human prostate cancer and microvessel endothelial cells, which was mediated by an angiogenesis inhibitor Semaphorin 3F. Moreover, we examined AKAP12 and Semaphorin 3F mRNA expression in 42 prostate cancer and 30 benign prostatic hyperplasia tissue samples, and found that the expression of AKAP12 and Semaphorin 3F mRNA was inversely associated with the degree of aggressiveness of prostate cancer cells and tissues. An ordinal logistic regression analysis indicates that there is a positive association between the expression of AKAP12 and Semaphorin 3F in prostate cancer, suggesting that the activation of Semaphorin 3F by SSeCKS/AKAP12 may be involved in prostate cancer progression and metastasis. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Epigenetic inactivation of the dioxin-responsive cytochrome P4501A1 gene in human prostate cancer.

    PubMed

    Okino, Steven T; Pookot, Deepa; Li, Long-Cheng; Zhao, Hong; Urakami, Shinji; Shiina, Hiroaki; Igawa, Mikio; Dahiya, Rajvir

    2006-08-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD; dioxin) is a toxic environmental contaminant that works through dioxin response elements (DRE) to activate gene expression. We tested the hypothesis that cancer-related epigenetic changes suppress dioxin activation of the cytochrome P4501A1 (CYP1A1) gene. 5-Aza-2'-deoxycytidine (5-aza-CdR), an inhibitor of DNA methylation, increases TCDD-inducible CYP1A1 mRNA expression in cancerous LNCaP cells but not in noncancerous PWR-1E and RWPE-1 cells (all human prostate cell lines). Bisulfite DNA sequencing shows that the TCDD-responsive CYP1A1 enhancer is highly methylated in LNCaP cells but not in RWPE-1 cells. In vivo footprinting experiments reveal that unmethylated DRE sites do not bind protein in response to TCDD in LNCaP cells, whereas inducible DRE occupancy occurs in RWPE-1 cells. Pretreatment of LNCaP cells with 5-aza-CdR partially restores TCDD-inducible DRE occupancy, showing that DNA methylation indirectly suppresses DRE occupancy. Chromatin immunoprecipitation experiments reveal that LNCaP cells lack trimethyl histone H3 lysine 4, a mark of active genes, on the CYP1A1 regulatory region, whereas this histone modification is prevalent in PWR-1E and RWPE-1 cells. We also analyzed CYP1A1 enhancer methylation in human prostate tissue DNA. We do not detect CYP1A1 enhancer methylation in 30 DNA samples isolated from noncancerous prostate tissue. In contrast, 11 of 30 prostate tumor DNA samples have detectable CYP1A1 enhancer methylation, indicating that it is hypermethylated in prostate tumors. This is the first report that shows that CYP1A1 is aberrantly hypermethylated in human prostate cancer and has an altered, inaccessible chromatin structure that suppresses its dioxin responsiveness.

  15. Boric acid inhibits human prostate cancer cell proliferation.

    PubMed

    Barranco, Wade T; Eckhert, Curtis D

    2004-12-08

    The role of boron in biology includes coordinated regulation of gene expression in mixed bacterial populations and the growth and proliferation of higher plants and lower animals. Here we report that boric acid, the dominant form of boron in plasma, inhibits the proliferation of prostate cancer cell lines, DU-145 and LNCaP, in a dose-dependent manner. Non-tumorigenic prostate cell lines, PWR-1E and RWPE-1, and the cancer line PC-3 were also inhibited, but required concentrations higher than observed human blood levels. Studies using DU-145 cells showed that boric acid induced a cell death-independent proliferative inhibition, with little effect on cell cycle stage distribution and mitochondrial function.

  16. A chemical relaxation study of human prostatic acid phosphatase.

    PubMed

    Shear, D B; Kustin, K

    1968-01-01

    Chemical relaxation methods and a dilution technique were applied to the study of the hydrolysis of p-nitrophenyl phosphate by human prostatic acid phosphatase. Although the reaction mechanism was not elucidated, rate constants and equilibrium constants were obtained for the reaction of enzyme and p-nitrophenol to form a complex. A slow, 2-sec relaxation effect which showed no concentration dependence was observed in various reaction mixtures, including some lacking the substrate and products of the hydrolytic reaction. The conclusion drawn is that there are two forms of the prostatic enzyme, which are normally in equilibrium with each other, but which undergo a relatively slow interconversion when this equilibrium is perturbed. A preliminary calculation indicates that these forms are present in the equilibrium ratio of 2:1.

  17. Genes overexpressed in different human solid cancers exhibit different tissue-specific expression profiles

    PubMed Central

    Bock Axelsen, Jacob; Lotem, Joseph; Sachs, Leo; Domany, Eytan

    2007-01-01

    We have analyzed gene expression in different normal human tissues and different types of solid cancers derived from these tissues. The cancers analyzed include brain (astrocytoma and glioblastoma), breast, colon, endometrium, kidney, liver, lung, ovary, prostate, skin, and thyroid cancers. Comparing gene expression in each normal tissue to 12 other normal tissues, we identified 4,917 tissue-selective genes that were selectively expressed in different normal tissues. We also identified 2,929 genes that are overexpressed at least 4-fold in the cancers compared with the normal tissue from which these cancers were derived. The overlap between these two gene groups identified 1,340 tissue-selective genes that are overexpressed in cancers. Different types of cancers, including different brain cancers arising from the same lineage, showed differences in the tissue-selective genes they overexpressed. Melanomas overexpressed the highest number of brain-selective genes and this may contribute to melanoma metastasis to the brain. Of all of the genes with tissue-selective expression, those selectively expressed in testis showed the highest frequency of genes that are overexpressed in at least two types of cancer. However, colon and prostate cancers did not overexpress any testis-selective gene. Nearly all of the genes with tissue-selective expression that are overexpressed in cancers showed selective expression in tissues different from the cancers' tissue of origin. Cancers aberrantly expressing such genes may acquire phenotypic alterations that contribute to cancer cell viability, growth, and metastasis. PMID:17664417

  18. Bisphenol A Promotes Human Prostate Stem-Progenitor Cell Self-Renewal and Increases In Vivo Carcinogenesis in Human Prostate Epithelium

    PubMed Central

    Hu, Wen-Yang; Shi, Guang-Bin; Hu, Dan-Ping; Majumdar, Shyama; Li, Guannan; Huang, Ke; Nelles, Jason L.; Ho, Shuk-Mei; Walker, Cheryl Lyn; Kajdacsy-Balla, Andre; van Breemen, Richard B.

    2014-01-01

    Previous studies in rodent models have shown that early-life exposure to bisphenol A (BPA) reprograms the prostate and enhances its susceptibility to hormonal carcinogenesis with aging. To determine whether the human prostate is similarly sensitive to BPA, the current study used human prostate epithelial stem-like cells cultured from prostates of young, disease-free donors. Similar to estradiol-17β (E2), BPA increased stem-progenitor cell self-renewal and expression of stem-related genes in a dose-dependent manner. Further, 10 nM BPA and E2 possessed equimolar membrane-initiated signaling with robust induction of p-Akt and p-Erk at 15 minutes. To assess in vivo carcinogenicity, human prostate stem-progenitor cells combined with rat mesenchyme were grown as renal grafts in nude mice, forming normal human prostate epithelium at 1 month. Developmental BPA exposure was achieved through oral administration of 100 or 250 μg BPA/kg body weight to hosts for 2 weeks after grafting, producing free BPA levels of 0.39 and 1.35 ng/mL serum, respectively. Carcinogenesis was driven by testosterone plus E2 treatment for 2 to 4 months to model rising E2 levels in aging men. The incidence of high-grade prostate intraepithelial neoplasia and adenocarcinoma markedly increased from 13% in oil-fed controls to 33% to 36% in grafts exposed in vivo to BPA (P < .05). Continuous developmental BPA exposure through in vitro (200 nM) plus in vivo (250 μg/kg body weight) treatments increased high-grade prostate intraepithelial neoplasia/cancer incidence to 45% (P < .01). Together, the present findings demonstrate that human prostate stem-progenitor cells are direct BPA targets and that developmental exposure to BPA at low doses increases hormone-dependent cancer risk in the human prostate epithelium. PMID:24424067

  19. 3D prostate histology image reconstruction: Quantifying the impact of tissue deformation and histology section location

    PubMed Central

    Gibson, Eli; Gaed, Mena; Gómez, José A.; Moussa, Madeleine; Pautler, Stephen; Chin, Joseph L.; Crukley, Cathie; Bauman, Glenn S.; Fenster, Aaron; Ward, Aaron D.

    2013-01-01

    Background: Guidelines for localizing prostate cancer on imaging are ideally informed by registered post-prostatectomy histology. 3D histology reconstruction methods can support this by reintroducing 3D spatial information lost during histology processing. The need to register small, high-grade foci drives a need for high accuracy. Accurate 3D reconstruction method design is impacted by the answers to the following central questions of this work. (1) How does prostate tissue deform during histology processing? (2) What spatial misalignment of the tissue sections is induced by microtome cutting? (3) How does the choice of reconstruction model affect histology reconstruction accuracy? Materials and Methods: Histology, paraffin block face and magnetic resonance images were acquired for 18 whole mid-gland tissue slices from six prostates. 7-15 homologous landmarks were identified on each image. Tissue deformation due to histology processing was characterized using the target registration error (TRE) after landmark-based registration under four deformation models (rigid, similarity, affine and thin-plate-spline [TPS]). The misalignment of histology sections from the front faces of tissue slices was quantified using manually identified landmarks. The impact of reconstruction models on the TRE after landmark-based reconstruction was measured under eight reconstruction models comprising one of four deformation models with and without constraining histology images to the tissue slice front faces. Results: Isotropic scaling improved the mean TRE by 0.8-1.0 mm (all results reported as 95% confidence intervals), while skew or TPS deformation improved the mean TRE by <0.1 mm. The mean misalignment was 1.1-1.9° (angle) and 0.9-1.3 mm (depth). Using isotropic scaling, the front face constraint raised the mean TRE by 0.6-0.8 mm. Conclusions: For sub-millimeter accuracy, 3D reconstruction models should not constrain histology images to the tissue slice front faces and should be

  20. Responsiveness of human prostate carcinoma bone tumors to interleukin-2 therapy in a mouse xenograft tumor model.

    PubMed

    Kocheril, S V; Grignon, D J; Wang, C Y; Maughan, R L; Montecillo, E J; Talati, B; Tekyi-Mensah, S; Pontes, J e; Hillman, G G

    1999-01-01

    We have tested an immunotherapy approach for the treatment of metastatic prostate carcinoma using a bone tumor model. Human PC-3 prostate carcinoma tumor cells were heterotransplanted into the femur cavity of athymic Balb/c nude mice. Tumor cells replaced marrow cells in the bone cavity, invaded adjacent bone and muscle tissues, and formed a palpable tumor at the hip joint. PC-3/IF cell lines, generated from bone tumors by serial in vivo passages, grew with faster kinetics in the femur and metastasized to inguinal lymph nodes. Established tumors were treated with systemic interleukin-2 (IL-2) injections. IL-2 significantly inhibited the formation of palpable tumors and prolonged mouse survival at nontoxic low doses. Histologically IL-2 caused vascular damage and infiltration of polymorphonuclear cells and lymphocytes in the tumor as well as necrotic areas with apoptotic cells. These findings suggest destruction of tumor cells by systemic IL-2 therapy and IL-2 responsiveness of prostate carcinoma bone tumors.

  1. Cholesteryl Ester Accumulation Induced by PTEN Loss and PI3K/AKT Activation Underlies Human Prostate Cancer Aggressiveness

    PubMed Central

    Yue, Shuhua; Li, Junjie; Lee, Seung-Young; Lee, Hyeon Jeong; Shao, Tian; Song, Bing; Cheng, Liang; Masterson, Timothy A.; Liu, Xiaoqi; Ratliff, Timothy L.; Cheng, Ji-Xin

    2014-01-01

    Summary Altered lipid metabolism is increasingly recognized as a signature of cancer cells. Enabled by label-free Raman spectromicroscopy, we performed quantitative analysis of lipogenesis at single cell level in human patient cancerous tissues. Our imaging data revealed an unexpected, aberrant accumulation of esterified cholesterol in lipid droplets of high-grade prostate cancer and metastases. Biochemical study showed that such cholesteryl ester accumulation was a consequence of loss of tumor suppressor PTEN and subsequent activation of PI3K/AKT pathway in prostate cancer cells. Furthermore, we found that such accumulation arose from significantly enhanced uptake of exogenous lipoproteins and required cholesterol esterification. Depletion of cholesteryl ester storage significantly reduced cancer proliferation, impaired cancer invasion capability, and suppressed tumor growth in mouse xenograft models with negligible toxicity. These findings open opportunities for diagnosing and treating prostate cancer by targeting the altered cholesterol metabolism. PMID:24606897

  2. Apparatus for Histological Validation of In Vivo and Ex Vivo Magnetic Resonance Imaging of the Human Prostate

    PubMed Central

    Bourne, Roger M.; Bailey, Colleen; Johnston, Edward William; Pye, Hayley; Heavey, Susan; Whitaker, Hayley; Siow, Bernard; Freeman, Alex; Shaw, Greg L.; Sridhar, Ashwin; Mertzanidou, Thomy; Hawkes, David J.; Alexander, Daniel C.; Punwani, Shonit; Panagiotaki, Eleftheria

    2017-01-01

    This article describes apparatus to aid histological validation of magnetic resonance imaging studies of the human prostate. The apparatus includes a 3D-printed patient-specific mold that facilitates aligned in vivo and ex vivo imaging, in situ tissue fixation, and tissue sectioning with minimal organ deformation. The mold and a dedicated container include MRI-visible landmarks to enable consistent tissue positioning and minimize image registration complexity. The inclusion of high spatial resolution ex vivo imaging aids in registration of in vivo MRI and histopathology data. PMID:28393049

  3. Correlation of concentrations of selected trace elements with Gleason grade of prostate tissues

    PubMed Central

    Kwiatek, W. M.; Banas, K.; Gajda, M.; Pawlicki, B.; Cichocki, T.

    2010-01-01

    The causes of prostate cancer are still obscure but some evidence indicates that there is a close connection between several trace elements and processes which may lead to malignant cells. In our study the microbeam synchrotron radiation X-ray fluorescence emission (micro-SRIXE) technique was applied for quantitative analysis of selected elements. For the first time, we correlate the concentrations of Mn, Fe, Cu, and Zn with the clinical stage of the prostate cancer at the time of operation (described by Gleason grade). Serial sections of prostate tissues were collected from patients undergoing radical prostatectomy. One section, stained with hematoxylin and eosin, was prepared for histopathological analysis; a second, adjacent unstained section was used in micro-SRIXE experiments. All experiments were performed at beamline L at HASYLAB, DESY, Germany. Our results seem to be valuable in light of the determination of the changes in the concentrations of trace elements as a potential diagnostic marker and their etiological involvement in the different stages of prostate diseases. PMID:20499115

  4. Histochemical study of apoptotic epithelial cells depending on testosterone in primary cultured rat prostatic tissues.

    PubMed

    Furuya, T; Kubo, M; Ueno, A; Fujii, Y; Baba, T; Ohno, S

    2000-04-01

    To clarify whether apoptosis can be induced in cultured rat prostatic epithelial cells, they were investigated at various time points, depending on different concentrations of testosterone. Ventral lobes of rat prostates were cultured as small pieces of tissues up to 14 days. They were examined by anti-Fas antibody immunostaining and also compared to findings revealed by in situ end-labelling (ISEL) technique. To clarify apoptotic nuclei at high resolution, the quick-freezing and deep-etching (QF-DE) method was also used, as reported before. The localization and appearance of Fas-positive cells were detected more widely and earlier than those of ISEL-positive cells, but both label-positive localizations were closely related to each other. In addition, they were detected more often in epithelial cells cultured with low testosterone concentrations. By the QF-DE method, chromatin fibers were found to be broken in spotty parts of apoptotic nuclei. We could control the concentration of testosterone in culture medium and detect the appearance of Fas antigen in cultured prostatic epithelial cells, followed by apoptotic changes. So, Fas and Fas-ligand system is one candidate for apoptosis in the prostate glands, depending on removal of hormonal testosterone.

  5. Linking γ-aminobutyric acid A receptor to epidermal growth factor receptor pathways activation in human prostate cancer.

    PubMed

    Wu, Weijuan; Yang, Qing; Fung, Kar-Ming; Humphreys, Mitchell R; Brame, Lacy S; Cao, Amy; Fang, Yu-Ting; Shih, Pin-Tsen; Kropp, Bradley P; Lin, Hsueh-Kung

    2014-03-05

    Neuroendocrine (NE) differentiation has been attributed to the progression of castration-resistant prostate cancer (CRPC). Growth factor pathways including the epidermal growth factor receptor (EGFR) signaling have been implicated in the development of NE features and progression to a castration-resistant phenotype. However, upstream molecules that regulate the growth factor pathway remain largely unknown. Using androgen-insensitive bone metastasis PC-3 cells and androgen-sensitive lymph node metastasis LNCaP cells derived from human prostate cancer (PCa) patients, we demonstrated that γ-aminobutyric acid A receptor (GABA(A)R) ligand (GABA) and agonist (isoguvacine) stimulate cell proliferation, enhance EGF family members expression, and activate EGFR and a downstream signaling molecule, Src, in both PC-3 and LNCaP cells. Inclusion of a GABA(A)R antagonist, picrotoxin, or an EGFR tyrosine kinase inhibitor, Gefitinib (ZD1839 or Iressa), blocked isoguvacine and GABA-stimulated cell growth, trans-phospohorylation of EGFR, and tyrosyl phosphorylation of Src in both PCa cell lines. Spatial distributions of GABAAR α₁ and phosphorylated Src (Tyr416) were studied in human prostate tissues by immunohistochemistry. In contrast to extremely low or absence of GABA(A)R α₁-positive immunoreactivity in normal prostate epithelium, elevated GABA(A)R α₁ immunoreactivity was detected in prostate carcinomatous glands. Similarly, immunoreactivity of phospho-Src (Tyr416) was specifically localized and limited to the nucleoli of all invasive prostate carcinoma cells, but negative in normal tissues. Strong GABAAR α₁ immunoreactivity was spatially adjacent to the neoplastic glands where strong phospho-Src (Tyr416)-positive immunoreactivity was demonstrated, but not in adjacent to normal glands. These results suggest that the GABA signaling is linked to the EGFR pathway and may work through autocrine or paracine mechanism to promote CRPC progression. Copyright © 2013 Elsevier

  6. Heterogeneity and clinical significance of ETV1 translocations in human prostate cancer

    PubMed Central

    Attard, G; Clark, J; Ambroisine, L; Mills, I G; Fisher, G; Flohr, P; Reid, A; Edwards, S; Kovacs, G; Berney, D; Foster, C; Massie, C E; Fletcher, A; De Bono, J S; Scardino, P; Cuzick, J; Cooper, C S

    2008-01-01

    A fluorescence in situ hybridisation (FISH) assay has been used to screen for ETV1 gene rearrangements in a cohort of 429 prostate cancers from patients who had been diagnosed by trans-urethral resection of the prostate. The presence of ETV1 gene alterations (found in 23 cases, 5.4%) was correlated with higher Gleason Score (P=0.001), PSA level at diagnosis (P=<0.0001) and clinical stage (P=0.017) but was not linked to poorer survival. We found that the six previously characterised translocation partners of ETV1 only accounted for 34% of ETV1 re-arrangements (eight out of 23) in this series, with fusion to the androgen-repressed gene C15orf21 representing the commonest event (four out of 23). In 5′-RACE experiments on RNA extracted from formalin-fixed tissue we identified the androgen-upregulated gene ACSL3 as a new 5′-translocation partner of ETV1. These studies report a novel fusion partner for ETV1 and highlight the considerable heterogeneity of ETV1 gene rearrangements in human prostate cancer. PMID:18594527

  7. Heterogeneity and clinical significance of ETV1 translocations in human prostate cancer.

    PubMed

    Attard, G; Clark, J; Ambroisine, L; Mills, I G; Fisher, G; Flohr, P; Reid, A; Edwards, S; Kovacs, G; Berney, D; Foster, C; Massie, C E; Fletcher, A; De Bono, J S; Scardino, P; Cuzick, J; Cooper, C S

    2008-07-22

    A fluorescence in situ hybridisation (FISH) assay has been used to screen for ETV1 gene rearrangements in a cohort of 429 prostate cancers from patients who had been diagnosed by trans-urethral resection of the prostate. The presence of ETV1 gene alterations (found in 23 cases, 5.4%) was correlated with higher Gleason Score (P=0.001), PSA level at diagnosis (P=<0.0001) and clinical stage (P=0.017) but was not linked to poorer survival. We found that the six previously characterised translocation partners of ETV1 only accounted for 34% of ETV1 re-arrangements (eight out of 23) in this series, with fusion to the androgen-repressed gene C15orf21 representing the commonest event (four out of 23). In 5'-RACE experiments on RNA extracted from formalin-fixed tissue we identified the androgen-upregulated gene ACSL3 as a new 5'-translocation partner of ETV1. These studies report a novel fusion partner for ETV1 and highlight the considerable heterogeneity of ETV1 gene rearrangements in human prostate cancer.

  8. Diffusion-weighted single-shot echo planar MR imaging of normal human prostate using different b values.

    PubMed

    Shi, Haojun; Kong, Xiangquan; Feng, Gansheng; Xu, Haibo; Liu, Dingxi; Yu, Qun

    2008-12-01

    This study examined the effect of different b values on diffusion-weighted MR imaging (DWI) of human prostate by using single-shot spin echo echo planar imaging (SE-EPI) sequences, observed the normal appearances and measured apparent diffusion coefficient (ADC) values in anatomical regions of normal prostate. Twenty-four healthy volunteers (mean age: 32 y) were studied by using a 1.5T system with a phased array surface multicoil. Two kinds of single-shot SE-EPI sequence were used to perform DWI in the prostate in volunteers, with five b values being 0, 30, 300, 500 to 1000 s/mm(2). The image quality with different imaging parameters was analyzed and the ADC values in anatomical regions of normal prostate were measured. DWI of prostate was successfully obtained in all volunteers. The images were of good quality, without artifacts containing pixels within the prostate. The contrast was good between the different anatomical regions of the prostatic gland, i.e., the peripheral zone (PZ), which exhibited higher signal intensity, and the central gland (CG). Signal intensity contrast was related to the magnitude of b values. The ADC values in PZ and CG were (1.27+/-0.22)x10(-3) mm(2)/s and (1.01+/-0.17)x10(-3) mm(2)/s, respectively. The ADC values were found to be significantly higher in PZ than in CG (P<0.05, paired t-test). Significant differences were found between the slice-selecting component and both the read-out and phase-encoding components of the ADC values. It is concluded that SE-EPI is a suitable DWI sequence for human prostate. The contrast between PZ and CG is good when b values are low, while the diffusion and ADC values are accurate when b values are high. ADC values are higher in PZ than in CG in normal prostate. Diffusional anisotropy is present in normal prostatic tissue.

  9. Humanized mice and tissue transplantation

    PubMed Central

    Kenney, Laurie L; Shultz, Leonard D.; Greiner, Dale L; Brehm, Michael A.

    2017-01-01

    Our understanding of the molecular pathways that control immune responses, particularly immunomodulatory molecules that control the extent and duration of an immune response, have led to new approaches in the field of transplantation immunology to induce allograft survival. These molecular pathways are being defined precisely in murine models, and are now being translated into clinical practice. However, many of the newly available drugs are human-specific reagents and furthermore, there exist many species-specific differences between mouse and human immune systems. Recent advances in the development of humanized mice, i.e., immunodeficient mice engrafted with functional human immune systems, have led to the availability of a small animal model for the study of human immune responses. Humanized mice represent an important pre-clinical model system for evaluation of new drugs as well as identification of the mechanisms underlying human allograft rejection without putting patients at risk. This review highlights recent advances in the development of humanized mice and their use as pre-clinical models for the study of human allograft responses. PMID:26588186

  10. Tissue Specificity of Human Disease Module

    PubMed Central

    Kitsak, Maksim; Sharma, Amitabh; Menche, Jörg; Guney, Emre; Ghiassian, Susan Dina; Loscalzo, Joseph; Barabási, Albert-László

    2016-01-01

    Genes carrying mutations associated with genetic diseases are present in all human cells; yet, clinical manifestations of genetic diseases are usually highly tissue-specific. Although some disease genes are expressed only in selected tissues, the expression patterns of disease genes alone cannot explain the observed tissue specificity of human diseases. Here we hypothesize that for a disease to manifest itself in a particular tissue, a whole functional subnetwork of genes (disease module) needs to be expressed in that tissue. Driven by this hypothesis, we conducted a systematic study of the expression patterns of disease genes within the human interactome. We find that genes expressed in a specific tissue tend to be localized in the same neighborhood of the interactome. By contrast, genes expressed in different tissues are segregated in distinct network neighborhoods. Most important, we show that it is the integrity and the completeness of the expression of the disease module that determines disease manifestation in selected tissues. This approach allows us to construct a disease-tissue network that confirms known and predicts unexpected disease-tissue associations. PMID:27748412

  11. Personalized Medicine Approaches in Prostate Cancer Employing Patient Derived 3D Organoids and Humanized Mice

    PubMed Central

    Bartucci, Monica; Ferrari, Anna C.; Kim, Isaac Yi; Ploss, Alexander; Yarmush, Martin; Sabaawy, Hatem E.

    2016-01-01

    Prostate cancer (PCa) is the most common malignancy and the second most common cause of cancer death in Western men. Despite its prevalence, PCa has proven very difficult to propagate in vitro. PCa represents a complex organ-like multicellular structure maintained by the dynamic interaction of tumoral cells with parenchymal stroma, endothelial and immune cells, and components of the extracellular matrix (ECM). The lack of PCa models that recapitulate this intricate system has hampered progress toward understanding disease progression and lackluster therapeutic responses. Tissue slices, monolayer cultures and genetically engineered mouse models (GEMM) fail to mimic the complexities of the PCa microenvironment or reproduce the diverse mechanisms of therapy resistance. Moreover, patient derived xenografts (PDXs) are expensive, time consuming, difficult to establish for prostate cancer, lack immune cell-tumor regulation, and often tumors undergo selective engraftments. Here, we describe an interdisciplinary approach using primary PCa and tumor initiating cells (TICs), three-dimensional (3D) tissue engineering, genetic and morphometric profiling, and humanized mice to generate patient-derived organoids for examining personalized therapeutic responses in vitro and in mice co-engrafted with a human immune system (HIS), employing adaptive T-cell- and chimeric antigen receptor- (CAR) immunotherapy. The development of patient specific therapies targeting the vulnerabilities of cancer, when combined with antiproliferative and immunotherapy approaches could help to achieve the full transformative power of cancer precision medicine. PMID:27446916

  12. Automatic classification of prostate stromal tissue in histological images using Haralick descriptors and Local Binary Patterns

    NASA Astrophysics Data System (ADS)

    Oliveira, D. L. L.; Nascimento, M. Z.; Neves, L. A.; Batista, V. R.; Godoy, M. F.; Jacomini, R. S.; Duarte, Y. A. S.; Arruda, P. F. F.; Neto, D. S.

    2014-03-01

    In this paper we presente a classification system that uses a combination of texture features from stromal regions: Haralick features and Local Binary Patterns (LBP) in wavelet domain. The system has five steps for classification of the tissues. First, the stromal regions were detected and extracted using segmentation techniques based on thresholding and RGB colour space. Second, the Wavelet decomposition was applied in the extracted regions to obtain the Wavelet coefficients. Third, the Haralick and LBP features were extracted from the coefficients. Fourth, relevant features were selected using the ANOVA statistical method. The classication (fifth step) was performed with Radial Basis Function (RBF) networks. The system was tested in 105 prostate images, which were divided into three groups of 35 images: normal, hyperplastic and cancerous. The system performance was evaluated using the area under the ROC curve and resulted in 0.98 for normal versus cancer, 0.95 for hyperplasia versus cancer and 0.96 for normal versus hyperplasia. Our results suggest that texture features can be used as discriminators for stromal tissues prostate images. Furthermore, the system was effective to classify prostate images, specially the hyperplastic class which is the most difficult type in diagnosis and prognosis.

  13. Xenotransplantation models to study the effects of toxicants on human fetal tissues.

    PubMed

    Spade, Daniel J; McDonnell, Elizabeth V; Heger, Nicholas E; Sanders, Jennifer A; Saffarini, Camelia M; Gruppuso, Philip A; De Paepe, Monique E; Boekelheide, Kim

    2014-12-01

    Many diseases that manifest throughout the lifetime are influenced by factors affecting fetal development. Fetal exposure to xenobiotics, in particular, may influence the development of adult diseases. Established animal models provide systems for characterizing both developmental biology and developmental toxicology. However, animal model systems do not allow researchers to assess the mechanistic effects of toxicants on developing human tissue. Human fetal tissue xenotransplantation models have recently been implemented to provide human-relevant mechanistic data on the many tissue-level functions that may be affected by fetal exposure to toxicants. This review describes the development of human fetal tissue xenotransplant models for testis, prostate, lung, liver, and adipose tissue, aimed at studying the effects of xenobiotics on tissue development, including implications for testicular dysgenesis, prostate disease, lung disease, and metabolic syndrome. The mechanistic data obtained from these models can complement data from epidemiology, traditional animal models, and in vitro studies to quantify the risks of toxicant exposures during human development. © 2014 Wiley Periodicals, Inc.

  14. Protein Phosphatase 2A Signaling in Human Prostate Cancer

    DTIC Science & Technology

    2011-06-01

    been shown to be involved in androgen-independent growth of human prostate cancer cells (Carson et al., 1999; Grethe and Porn -Ares, 2006; Murillo et... Porn -Ares MI. (2006). p38 MAPK regulates phosphorylation of Bad via PP2A- dependent suppression of the MEK1/2-ERK1/2 survival pathway in TNF-alpha...threonine phosphatases implicated in cell growth and sig- nalling. Biochem J 2001;353:417–39. 15. Grethe S, Porn -Ares MI. p38 MAPK regulates

  15. Functional Erythropoietin Receptors Expressed by Human Prostate Cancer Cells

    DTIC Science & Technology

    2006-10-01

    carcinoma cell line (PC-3). Invest Urol, 1979. 17(1): p. 16-23. 11. Yoshimura, A., A.D. D’Andrea, and H.F. Lodish , Friend spleen focus-forming virus...receptor expression in human prostate cancer. Mod Pathol, 2004. 13. Socolovsky, M., A.E. Fallon, S. Wang, C. Brugnara, and H.F. Lodish , Fetal anemia and...Socolovsky, M., H. Nam, M.D. Fleming, V.H. Haase, C. Brugnara, and H.F. Lodish , Ineffective erythropoiesis in Stat5a(-/-)5b(-/-) mice due to decreased

  16. Grating-based tomography of human tissues

    NASA Astrophysics Data System (ADS)

    Müller, Bert; Schulz, Georg; Mehlin, Andrea; Herzen, Julia; Lang, Sabrina; Holme, Margaret; Zanette, Irene; Hieber, Simone; Deyhle, Hans; Beckmann, Felix; Pfeiffer, Franz; Weitkamp, Timm

    2012-07-01

    The development of therapies to improve our health requires a detailed knowledge on the anatomy of soft tissues from the human body down to the cellular level. Grating-based phase contrast micro computed tomography using synchrotron radiation provides a sensitivity, which allows visualizing micrometer size anatomical features in soft tissue without applying any contrast agent. We show phase contrast tomography data of human brain, tumor vessels and constricted arteries from the beamline ID 19 (ESRF) and urethral tissue from the beamline W2 (HASYLAB/DESY) with micrometer resolution. Here, we demonstrate that anatomical features can be identified within brain tissue as well known from histology. Using human urethral tissue, the application of two photon energies is compared. Tumor vessels thicker than 20 μm can be perfectly segmented. The morphology of coronary arteries can be better extracted in formalin than after paraffin embedding.

  17. 3D conformal MRI-controlled transurethral ultrasound prostate therapy: validation of numerical simulations and demonstration in tissue-mimicking gel phantoms.

    PubMed

    Burtnyk, Mathieu; N'Djin, William Apoutou; Kobelevskiy, Ilya; Bronskill, Michael; Chopra, Rajiv

    2010-11-21

    MRI-controlled transurethral ultrasound therapy uses a linear array of transducer elements and active temperature feedback to create volumes of thermal coagulation shaped to predefined prostate geometries in 3D. The specific aims of this work were to demonstrate the accuracy and repeatability of producing large volumes of thermal coagulation (>10 cc) that conform to 3D human prostate shapes in a tissue-mimicking gel phantom, and to evaluate quantitatively the accuracy with which numerical simulations predict these 3D heating volumes under carefully controlled conditions. Eleven conformal 3D experiments were performed in a tissue-mimicking phantom within a 1.5T MR imager to obtain non-invasive temperature measurements during heating. Temperature feedback was used to control the rotation rate and ultrasound power of transurethral devices with up to five 3.5 × 5 mm active transducer elements. Heating patterns shaped to human prostate geometries were generated using devices operating at 4.7 or 8.0 MHz with surface acoustic intensities of up to 10 W cm(-2). Simulations were informed by transducer surface velocity measurements acquired with a scanning laser vibrometer enabling improved calculations of the acoustic pressure distribution in a gel phantom. Temperature dynamics were determined according to a FDTD solution to Pennes' BHTE. The 3D heating patterns produced in vitro were shaped very accurately to the prostate target volumes, within the spatial resolution of the MRI thermometry images. The volume of the treatment difference falling outside ± 1 mm of the target boundary was, on average, 0.21 cc or 1.5% of the prostate volume. The numerical simulations predicted the extent and shape of the coagulation boundary produced in gel to within (mean ± stdev [min, max]): 0.5 ± 0.4 [-1.0, 2.1] and -0.05 ± 0.4 [-1.2, 1.4] mm for the treatments at 4.7 and 8.0 MHz, respectively. The temperatures across all MRI thermometry images were predicted within -0.3 ± 1.6 °C and 0

  18. 3D conformal MRI-controlled transurethral ultrasound prostate therapy: validation of numerical simulations and demonstration in tissue-mimicking gel phantoms

    NASA Astrophysics Data System (ADS)

    Burtnyk, Mathieu; Apoutou N'Djin, William; Kobelevskiy, Ilya; Bronskill, Michael; Chopra, Rajiv

    2010-11-01

    MRI-controlled transurethral ultrasound therapy uses a linear array of transducer elements and active temperature feedback to create volumes of thermal coagulation shaped to predefined prostate geometries in 3D. The specific aims of this work were to demonstrate the accuracy and repeatability of producing large volumes of thermal coagulation (>10 cc) that conform to 3D human prostate shapes in a tissue-mimicking gel phantom, and to evaluate quantitatively the accuracy with which numerical simulations predict these 3D heating volumes under carefully controlled conditions. Eleven conformal 3D experiments were performed in a tissue-mimicking phantom within a 1.5T MR imager to obtain non-invasive temperature measurements during heating. Temperature feedback was used to control the rotation rate and ultrasound power of transurethral devices with up to five 3.5 × 5 mm active transducer elements. Heating patterns shaped to human prostate geometries were generated using devices operating at 4.7 or 8.0 MHz with surface acoustic intensities of up to 10 W cm-2. Simulations were informed by transducer surface velocity measurements acquired with a scanning laser vibrometer enabling improved calculations of the acoustic pressure distribution in a gel phantom. Temperature dynamics were determined according to a FDTD solution to Pennes' BHTE. The 3D heating patterns produced in vitro were shaped very accurately to the prostate target volumes, within the spatial resolution of the MRI thermometry images. The volume of the treatment difference falling outside ±1 mm of the target boundary was, on average, 0.21 cc or 1.5% of the prostate volume. The numerical simulations predicted the extent and shape of the coagulation boundary produced in gel to within (mean ± stdev [min, max]): 0.5 ± 0.4 [-1.0, 2.1] and -0.05 ± 0.4 [-1.2, 1.4] mm for the treatments at 4.7 and 8.0 MHz, respectively. The temperatures across all MRI thermometry images were predicted within -0.3 ± 1.6 °C and 0

  19. Differential expression of HSPA1 and HSPA2 proteins in human tissues; tissue microarray-based immunohistochemical study.

    PubMed

    Scieglinska, Dorota; Piglowski, Wojciech; Chekan, Mykola; Mazurek, Agnieszka; Krawczyk, Zdzisław

    2011-04-01

    In the present study we determined the expression pattern of HSPA1 and HSPA2 proteins in various normal human tissues by tissue-microarray based immunohistochemical analysis. Both proteins belong to the HSPA (HSP70) family of heat shock proteins. The HSPA2 is encoded by the gene originally defined as testis-specific, while HSPA1 is encoded by the stress-inducible genes (HSPA1A and HSPA1B). Our study revealed that both proteins are expressed only in some tissues from the 24 ones examined. HSPA2 was detected in adrenal gland, bronchus, cerebellum, cerebrum, colon, esophagus, kidney, skin, small intestine, stomach and testis, but not in adipose tissue, bladder, breast, cardiac muscle, diaphragm, liver, lung, lymph node, pancreas, prostate, skeletal muscle, spleen, thyroid. Expression of HSPA1 was detected in adrenal gland, bladder, breast, bronchus, cardiac muscle, esophagus, kidney, prostate, skin, but not in other tissues examined. Moreover, HSPA2 and HSPA1 proteins were found to be expressed in a cell-type-specific manner. The most pronounced cell-type expression pattern was found for HSPA2 protein. In the case of stratified squamous epithelia of the skin and esophagus, as well as in ciliated pseudostratified columnar epithelium lining respiratory tract, the HSPA2 positive cells were located in the basal layer. In the colon, small intestine and bronchus epithelia HSPA2 was detected in goblet cells. In adrenal gland cortex HSPA2 expression was limited to cells of zona reticularis. The presented results clearly show that certain human tissues constitutively express varying levels of HSPA1 and HSPA2 proteins in a highly differentiated way. Thus, our study can help designing experimental models suitable for cell- and tissue-type-specific functional differences between HSPA2 and HSPA1 proteins in human tissues.

  20. Daytime Blue Light Enhances the Nighttime Circadian Melatonin Inhibition of Human Prostate Cancer Growth

    PubMed Central

    Dauchy, Robert T; Hoffman, Aaron E; Wren-Dail, Melissa A; Hanifin, John P; Warfield, Benjamin; Brainard, George C; Xiang, Shulin; Yuan, Lin; Hill, Steven M; Belancio, Victoria P; Dauchy, Erin M; Smith, Kara; Blask, David E

    2015-01-01

    Light controls pineal melatonin production and temporally coordinates circadian rhythms of metabolism and physiology in normal and neoplastic tissues. We previously showed that peak circulating nocturnal melatonin levels were 7-fold higher after daytime spectral transmittance of white light through blue-tinted (compared with clear) rodent cages. Here, we tested the hypothesis that daytime blue-light amplification of nocturnal melatonin enhances the inhibition of metabolism, signaling activity, and growth of prostate cancer xenografts. Compared with male nude rats housed in clear cages under a 12:12-h light:dark cycle, rats in blue-tinted cages (with increased transmittance of 462–484 nm and decreased red light greater than 640 nm) evinced over 6-fold higher peak plasma melatonin levels at middark phase (time, 2400), whereas midlight-phase levels (1200) were low (less than 3 pg/mL) in both groups. Circadian rhythms of arterial plasma levels of linoleic acid, glucose, lactic acid, pO2, pCO2, insulin, leptin, and corticosterone were disrupted in rats in blue cages as compared with the corresponding entrained rhythms in clear-caged rats. After implantation with tissue-isolated PC3 human prostate cancer xenografts, tumor latency-to-onset of growth and growth rates were markedly delayed, and tumor cAMP levels, uptake–metabolism of linoleic acid, aerobic glycolysis (Warburg effect), and growth signaling activities were reduced in rats in blue compared with clear cages. These data show that the amplification of nighttime melatonin levels by exposing nude rats to blue light during the daytime significantly reduces human prostate cancer metabolic, signaling, and proliferative activities. PMID:26678364

  1. Daytime Blue Light Enhances the Nighttime Circadian Melatonin Inhibition of Human Prostate Cancer Growth.

    PubMed

    Dauchy, Robert T; Hoffman, Aaron E; Wren-Dail, Melissa A; Hanifin, John P; Warfield, Benjamin; Brainard, George C; Xiang, Shulin; Yuan, Lin; Hill, Steven M; Belancio, Victoria P; Dauchy, Erin M; Smith, Kara; Blask, David E

    2015-12-01

    Light controls pineal melatonin production and temporally coordinates circadian rhythms of metabolism and physiology in normal and neoplastic tissues. We previously showed that peak circulating nocturnal melatonin levels were 7-fold higher after daytime spectral transmittance of white light through blue-tinted (compared with clear) rodent cages. Here, we tested the hypothesis that daytime blue-light amplification of nocturnal melatonin enhances the inhibition of metabolism, signaling activity, and growth of prostate cancer xenografts. Compared with male nude rats housed in clear cages under a 12:12-h light:dark cycle, rats in blue-tinted cages (with increased transmittance of 462-484 nm and decreased red light greater than 640 nm) evinced over 6-fold higher peak plasma melatonin levels at middark phase (time, 2400), whereas midlight-phase levels (1200) were low (less than 3 pg/mL) in both groups. Circadian rhythms of arterial plasma levels of linoleic acid, glucose, lactic acid, pO2, pCO2, insulin, leptin, and corticosterone were disrupted in rats in blue cages as compared with the corresponding entrained rhythms in clear-caged rats. After implantation with tissue-isolated PC3 human prostate cancer xenografts, tumor latency-to-onset of growth and growth rates were markedly delayed, and tumor cAMP levels, uptake-metabolism of linoleic acid, aerobic glycolysis (Warburg effect), and growth signaling activities were reduced in rats in blue compared with clear cages. These data show that the amplification of nighttime melatonin levels by exposing nude rats to blue light during the daytime significantly reduces human prostate cancer metabolic, signaling, and proliferative activities.

  2. The activation of OR51E1 causes growth suppression of human prostate cancer cells.

    PubMed

    Maßberg, Désirée; Jovancevic, Nikolina; Offermann, Anne; Simon, Annika; Baniahmad, Aria; Perner, Sven; Pungsrinont, Thanakorn; Luko, Katarina; Philippou, Stathis; Ubrig, Burkhard; Heiland, Markus; Weber, Lea; Altmüller, Janine; Becker, Christian; Gisselmann, Günter; Gelis, Lian; Hatt, Hanns

    2016-07-26

    The development of prostate cancer (PCa) is regulated by the androgen-dependent activity of the androgen receptor (AR). Androgen-deprivation therapy (ADT) is therefore the gold standard treatment to suppress malignant progression of PCa. Nevertheless, due to the development of castration resistance, recurrence of disease after initial response to ADT is a major obstacle to successful treatment. As G-protein coupled receptors play a fundamental role in PCa physiology, they might represent promising alternative or combinatorial targets for advanced diseases. Here, we verified gene expression of the olfactory receptors (ORs) OR51E1 [prostate-specific G-protein coupled receptor 2 (PSGR2)] and OR51E2 (PSGR) in human PCa tissue by RNA-Seq analysis and RT-PCR and elucidated the subcellular localization of both receptor proteins in human prostate tissue. The OR51E1 agonist nonanoic acid (NA) leads to the phosphorylation of various protein kinases and growth suppression of the PCa cell line LNCaP. Furthermore, treatment with NA causes reduction of androgen-mediated AR target gene expression. Interestingly, NA induces cellular senescence, which coincides with reduced E2F1 mRNA levels. In contrast, treatment with the structurally related compound 1-nonanol or the OR2AG1 agonist amyl butyrate, neither of which activates OR51E1, did not lead to reduced cell growth or an induction of cellular senescence. However, decanoic acid, another OR51E1 agonist, also induces cellular senescence. Thus, our results suggest the involvement of OR51E1 in growth processes of PCa cells and its impact on AR-mediated signaling. These findings provide novel evidences to support the functional importance of ORs in PCa pathogenesis.

  3. Worldwide Prevalence of Human Papillomavirus and Relative Risk of Prostate Cancer: A Meta-analysis.

    PubMed

    Yang, Lin; Xie, Shuanghua; Feng, Xiaoshuang; Chen, Yuheng; Zheng, Tongzhang; Dai, Min; Zhou, Cindy Ke; Hu, Zhibin; Li, Ni; Hang, Dong

    2015-10-06

    Despite the increasing number of studies conducted recently to evaluate the association between HPV infections and the risk of prostate cancer, the results remain inconclusive. Furthermore, the prevalence and distribution of overall and individual HPV types worldwide in prostate cancer has not been reported until now. Therefore, we estimated the prevalence of HPV in prostate cancer by pooling data of 46 studies with 4919 prostate cancer cases, taking into account the heterogeneity of major related parameters, including study region, specimen type, HPV DNA source, detection method, publication calendar period and Gleason score. Moreover, we tested the association of HPV infections with prostate cancer risks by a meta-analysis of 26 tissue-based case-control studies. We found that the prevalence of HPV infection was 18.93% (95% CI = 17.84-20.05%) in prostate cancer cases, and most of which were high-risk HPV types (17.73%, 95% CI = 16.52-18.99%). The prevalence varied by region, PCR primers used, publication calendar period and Gleason score. Our study also showed a significantly increased risk of prostate cancer with the positivity of overall HPV detected in prostate tissues (OR = 1.79, 95% CI = 1.29-2.49) and revealed the geographic variation of association strength (P < 0.001). In conclusion, HPV infections may contribute to the risk of prostate cancer.

  4. Worldwide Prevalence of Human Papillomavirus and Relative Risk of Prostate Cancer: A Meta-analysis

    PubMed Central

    Yang, Lin; Xie, Shuanghua; Feng, Xiaoshuang; Chen, Yuheng; Zheng, Tongzhang; Dai, Min; Ke Zhou, Cindy; Hu, Zhibin; Li, Ni; Hang, Dong

    2015-01-01

    Despite the increasing number of studies conducted recently to evaluate the association between HPV infections and the risk of prostate cancer, the results remain inconclusive. Furthermore, the prevalence and distribution of overall and individual HPV types worldwide in prostate cancer has not been reported until now. Therefore, we estimated the prevalence of HPV in prostate cancer by pooling data of 46 studies with 4919 prostate cancer cases, taking into account the heterogeneity of major related parameters, including study region, specimen type, HPV DNA source, detection method, publication calendar period and Gleason score. Moreover, we tested the association of HPV infections with prostate cancer risks by a meta-analysis of 26 tissue-based case-control studies. We found that the prevalence of HPV infection was 18.93% (95% CI = 17.84–20.05%) in prostate cancer cases, and most of which were high-risk HPV types (17.73%, 95% CI = 16.52–18.99%). The prevalence varied by region, PCR primers used, publication calendar period and Gleason score. Our study also showed a significantly increased risk of prostate cancer with the positivity of overall HPV detected in prostate tissues (OR = 1.79, 95% CI = 1.29–2.49) and revealed the geographic variation of association strength (P < 0.001). In conclusion, HPV infections may contribute to the risk of prostate cancer. PMID:26441160

  5. EphA6 promotes angiogenesis and prostate cancer metastasis and is associated with human prostate cancer progression

    PubMed Central

    Xie, Chongwei; Wu, Zhiyuan; Kang, Zhihua; Fang, Zujun; Su, Bing; Guan, Ming

    2015-01-01

    Metastasis is the primary cause of prostate cancer (CaP)-related death. We investigate the molecular, pathologic and clinical outcome associations of EphA6 expression and CaP metastasis. The expression profiling of Eph receptors (Ephs) and their ephrin ligands was performed in parental and metastatic CaP cell lines. Among Ephs and ephrins, only EphA6 is consistently overexpressed in metastatic CaP cells. Metastatic potential of EphA6 is assessed by RNAi in a CaP spontaneous metastasis mouse model. EphA6 knock-down in human PC-3M cells causes decreased invasion in vitro and reduced lung and lymph node metastasis in vivo. In addition, knock-down of EphA6 decreases tube formation in vitro and angiogenesis in vivo. EphA6 mRNA expression is higher in 112 CaP tumor samples compared with benign tissues from 58 benign prostate hyperplasia patients. Positive correlation was identified between EphA6 expression and vascular invasion, neural invasion, PSA level, and TNM staging in CaP cases. Further, genome-wide gene expression analysis in EphA6 knock-down cells identified a panel of differentially regulated genes including PIK3IPA, AKT1, and EIF5A2, which could contribute to EphA6-regulated cancer progression. These findings identify EphA6 as a potentially novel metastasis gene which positively correlates with CaP progression. EphA6 may be a therapeutic target in metastatic CaP. PMID:26041887

  6. NCI’s Cooperative Human Tissue Network

    Cancer.gov

    Quality biospecimens are a foundational resource for cancer research. One of NCI’s longest running biospecimen programs is the Cooperative Human Tissue Network, a resource mainly for basic discovery and early translational research.

  7. Quantification of phase I / II metabolizing enzyme gene expression and polycyclic aromatic hydrocarbon-DNA adduct levels in human prostate

    PubMed Central

    John, Kaarthik; Ragavan, Narasimhan; Pratt, M. Margaret; Singh, Paras B.; Al-Buheissi, Salah; Matanhelia, Shyam S.; Phillips, David H.; Poirier, Miriam C.; Martin, Francis L.

    2008-01-01

    BACKGROUND Studies of migrant populations suggest that dietary and/or environmental factors play a crucial role in the aetiology of prostatic adenocarcinoma (CaP). The human prostate consists of the peripheral zone (PZ), transition zone (TZ) and central zone (CZ); CaP occurs most often in the PZ. METHODS To investigate the notion that an underlying differential expression of phase I/II genes, and/or the presence of polycyclic aromatic hydrocarbon (PAH)-DNA adducts might explain the elevated PZ susceptibility, we examined prostate tissues (matched tissue sets consisting of PZ and TZ) from men undergoing radical retropubic prostatectomy for CaP (n=26) or cystoprostatectomy (n=1). Quantitative gene expression analysis was employed for cytochrome P450 (CYP) isoforms CYP1A1, CYP1B1 and CYP1A2, as well as N-acetyltransferase 1 and 2 (NAT1 and NAT2) and catechol-O-methyl transferase (COMT). RESULTS CYP1B1, NAT1 and COMT were expressed in all tissue sets; levels of CYP1B1 and NAT1 were consistently higher in the PZ compared to TZ. Immunohistochemistry confirmed the presence of CYP1B1 (nuclear-associated and primarily in basal epithelial cells) and NAT1. Tissue sections from 23 of these aforementioned 27 matched tissue sets were analyzed for PAH-DNA adduct levels using antiserum elicited against DNA modified with r7, t8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydro-benzo[a]pyrene (BPDE). PAH-DNA adduct levels were highest in glandular epithelial cells, but a comparison of PZ and TZ showed no significant differences. CONCLUSION Although expression of activating and/or detoxifying enzymes may be higher in the PZ, PAH-DNA adduct levels appear to be similar in both zones. Therefore, factors other than PAH-DNA adducts may be responsible for promotion of tumour formation in the human prostate. PMID:19143007

  8. In vivo cryoablation of prostate tissue with temperature monitoring by optoacoustic imaging

    NASA Astrophysics Data System (ADS)

    Petrova, Elena V.; Motamedi, Massoud; Oraevsky, Alexander A.; Ermilov, Sergey A.

    2016-03-01

    Cryoablation of prostate cancer is an FDA approved clinical procedure, which involves repetitive rapid cooling of a lesion to lethal temperatures of -40°C and below. The major drawback of the technique is the insufficient control over the fast thermal processes that may result in severe complications (impotence, incontinence, perforation of the rectal wall) and morbidity. The developed optoacoustic imaging technique provides non-invasive real-time temperature mapping of tissue adjacent to prostate and enables more efficient control over the procedure, which is necessary to reduce side effects and accelerate the physician's learning curve. In these studies we successfully demonstrated real-time transrectal optoacoustic imaging during prostate cryoablation in live canine model focused on optoacoustic thermography of the rectal wall within the depth of 1cm. Our method utilized previously discovered universal thermal dependence of the normalized optoacoustic response of blood. Nanosecond-pulse radiation of Ti-Sapphire laser tuned to the isosbestic point of hemoglobin (802+/-3 nm) was delivered via fiberoptic illuminators assembled on both sides of the linear array of the 128-channel transrectal ultrasound probe. Temperature readouts at discrete locations inside and nearby prostate were also performed using standard transperineal needle sensors. The effect of homeostasis on optoacoustic imaging in live tissue was examined during cooling and shown to be significant only within the range of +/-1.5°C in respect to the body temperature. Accuracy of in vivo optoacoustic temperature measurements was determined as +/-2°C for the range of temperature from +35 to -15°C, which is more than sufficient for tracking the essential isotherms in the course of clinical procedures.

  9. Honokiol, a natural plant product, inhibits the bone metastatic growth of human prostate cancer cells.

    PubMed

    Shigemura, Katsumi; Arbiser, Jack L; Sun, Shi-Yong; Zayzafoon, Majd; Johnstone, Peter A S; Fujisawa, Masato; Gotoh, Akinobu; Weksler, Babette; Zhau, Haiyen E; Chung, Leland W K

    2007-04-01

    Honokiol, a soluble nontoxic natural product derived from Magnolia spp., has been shown to induce apoptosis in malignant cells. The effect of honokiol and the combined therapy with docetaxel on prostate cancer (PCa) growth and bone metastasis was investigated in experimental models. The in vitro proapoptotic effects of honokiol on human androgen-dependent and -independent PCa, bone marrow, bone marrow-derived endothelial, and prostate stroma cells were investigated. Honokiol-induced activation of caspases was evaluated by Western blot and FACS analysis. To confirm the cytotoxicity of honokiol, mice bone was inoculated in vivo with androgen-independent PCa, C4-2 cells and the effects of honokiol and/or docetaxel on PCa growth in bone were evaluated. Daily honokiol (100 mg/kg) and/or weekly docetaxel (5 mg/kg) were injected intraperitoneally for 6 weeks. PCa growth in mouse bone was evaluated by radiography, serum prostate-specific antigen (PSA) and tissue immunohistochemistry. Honokiol induced apoptosis in all cell lines tested. In PCa cells honokiol induced apoptosis via the activation of caspases 3, 8, and 9 and the cleavage of poly-adenosine diphosphate ribose polymerase in a dose- and time-dependent manner. Honokiol was shown to inhibit the growth and depress serum PSA in mice harboring C4-2 xenografts in the skeleton and the combination with docetaxel showed additive effects that inhibited further growth without evidence of systemic toxicity. Immunohistochemical staining confirmed honokiol exhibited growth-inhibitory, apoptotic, and antiangiogenic effects on PCa xenografts. The combination of honokiol and low-dose docetaxel may be used to improve patient outcome in androgen-independent prostate cancer with bone metastasis. (c) 2007 American Cancer Society.

  10. Targeted proteomic approach in prostatic tissue: a panel of potential biomarkers for cancer detection

    PubMed Central

    Terracciano, Rosa; Damiano, Rocco; Savino, Rocco; Sindona, Giovanni; Napoli, Anna

    2016-01-01

    Prostate cancer (PCa) is the sixth highest causes of cancer-related deaths in men. The molecular events underlying its behavior and evolution are not completely understood. Prostate-specific antigen (PSA) is the only approved Food and Drug Administration biomarker. A panel of ten stage-specific tumoral and adjacent non tumoral tissues from patients affected by PCa (Gleason score 6, 3+3; PSA 10 ÷19 ng/ml) was investigated by MS-based proteomics approach. The proposed method was based on identifying the base-soluble proteins from tissue, established an efficient study, which lead to a deeper molecular perspective understanding of the PCa. A total of 164 proteins were found and 132 of these were evaluated differentially expressed in tumoral tissues. The Ingenuity Pathway Analysis (IPA) showed that among all dataset obtained, 105 molecules were involved in epithelial neoplasia with a p-value of 3.62E-05, whereas, only 11 molecules detected were ascribed to sentinel tissue and bodily fluids. PMID:27713912

  11. Targeting the Human Complement Membrane Attack Complex to Selectively Kill Prostate Cancer Cells

    DTIC Science & Technology

    2014-12-01

    1 AD_________________ Award Number: W81XWH-11-1-0309 TITLE: Targeting the Human Complement Membrane Attack Complex to Selectively Kill Prostate...Attack Complex to Selectively Kill Prostate Cancer Cells 5b. GRANT NUMBER W81XWH-11-1-0309 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Samuel R...leading to the lytic death of PSA- producing prostate cancer cells as well as a significant bystander effect and killing of non-PSA producing cancer

  12. Melanin content of hamster tissues, human tissues, and various melanomas

    SciTech Connect

    Watts, K.P.; Fairchild, R.G.; Slatkin, D.N.; Greenberg, D.; Packer, S.; Atkins, H.L.; Hannon, S.J.

    1981-02-01

    Melanin content (percentage by weight) was determined in both pigmented and nonpigmented tissues of Syrian golden hamsters bearing Greene melanoma. Melanin content was also measured in various other melanoma models (B-16 in C57 mice, Harding-Passey in BALB/c mice, and KHDD in C3H mice) and in nine human melanomas, as well as in selected normal tissues. The purpose was to evaluate the possible efficacy of chlorpromazine, which is known to bind to melanin, as a vehicle for boron transport in neutron capture therapy. Successful therapy would depend upon selective uptake and absolute concentration of borated compounds in tumors; these parameters will in turn depend upon melanin concentration in melanomas and nonpigmented ''background'' tissues. Hamster whole eyes, hamster melanomas, and other well-pigmented animal melanomas were found to contain 0.3 to 0.8% melanin by weight, whereas human melanomas varied from 0.1 to 0.9% (average, 0.35%). Other tissues, with the exception of skin, were lower in content by a factor of greater than or equal to30. Melanin pigment was extracted from tissues, and the melanin content was determined spectrophotometrically. Measurements were found to be sensitive to the presence of other proteins. Previous procedures for isolating and quantifying melanin often neglected the importance of removing proteins and other interfering nonmelanic substances.

  13. Differential vitamin D 24-hydroxylase/CYP24A1 gene promoter methylation in endothelium from benign and malignant human prostate

    PubMed Central

    Karpf, Adam R; Omilian, Angela R; Bshara, Wiam; Tian, Lili; Tangrea, Michael A; Morrison, Carl D; Johnson, Candace S

    2011-01-01

    Epigenetic alterations occur in tumor-associated vessels in the tumor microenvironment. Methylation of the CYP24A1 gene promoter differs in endothelial cells isolated from tumors and non-tumor microenvironments in mice. The epigenetic makeup of endothelial cells of human tumor-associated vasculature is unknown due to difficulty of isolating endothelial cells populations from a heterogeneous tissue microenvironment. To ascertain CYP24A1 promoter methylation in tumor-associated endothelium, we utilized laser microdissection guided by CD31 immunohistochemistry to procure endothelial cells from human prostate tumor specimens. Prostate tissues were obtained following robotic radical prostatectomy from men with clinically localized prostate cancer. Adjacent histologically benign prostate tissues were used to compare endothelium from benign versus tumor microenvironments. Sodium bisulfite sequencing of CYP24A1 promoter region showed that the average CYP24A1 promoter methylation in the endothelium was 20% from the tumor microenvironment compared with 8.2% in the benign microenvironment (p < 0.05). A 2-fold to 17-fold increase in CYP24A1 promoter methylation was observed in the prostate tumor endothelium compared with the matched benign prostate endothelium in four patient samples, while CYP24A1 promoter methylation remained unchanged in two patient samples. In addition, there is no correlation of the level of CYP24A1 promoter methylation in prostate tumor-associated endothelium with that of epithelium/stroma. This study demonstrates that the CYP24A1 promoter is methylated in tumor-associated endothelium, indicating that epigenetic alterations in CYP24A1 may play a role in determining the phenotype of tumor-associated vasculature in the prostate tumor microenvironment. PMID:21725204

  14. Variation in alternative splicing across human tissues

    PubMed Central

    Yeo, Gene; Holste, Dirk; Kreiman, Gabriel; Burge, Christopher B

    2004-01-01

    Background Alternative pre-mRNA splicing (AS) is widely used by higher eukaryotes to generate different protein isoforms in specific cell or tissue types. To compare AS events across human tissues, we analyzed the splicing patterns of genomically aligned expressed sequence tags (ESTs) derived from libraries of cDNAs from different tissues. Results Controlling for differences in EST coverage among tissues, we found that the brain and testis had the highest levels of exon skipping. The most pronounced differences between tissues were seen for the frequencies of alternative 3' splice site and alternative 5' splice site usage, which were about 50 to 100% higher in the liver than in any other human tissue studied. Quantifying differences in splice junction usage, the brain, pancreas, liver and the peripheral nervous system had the most distinctive patterns of AS. Analysis of available microarray expression data showed that the liver had the most divergent pattern of expression of serine-arginine protein and heterogeneous ribonucleoprotein genes compared to the other human tissues studied, possibly contributing to the unusually high frequency of alternative splice site usage seen in liver. Sequence motifs enriched in alternative exons in genes expressed in the brain, testis and liver suggest specific splicing factors that may be important in AS regulation in these tissues. Conclusions This study distinguishes the human brain, testis and liver as having unusually high levels of AS, highlights differences in the types of AS occurring commonly in different tissues, and identifies candidate cis-regulatory elements and trans-acting factors likely to have important roles in tissue-specific AS in human cells. PMID:15461793

  15. LINE-1 methylation status in prostate cancer and non-neoplastic tissue adjacent to tumor in association with mortality.

    PubMed

    Fiano, Valentina; Zugna, Daniela; Grasso, Chiara; Trevisan, Morena; Delsedime, Luisa; Molinaro, Luca; Gillio-Tos, Anna; Merletti, Franco; Richiardi, Lorenzo

    2017-01-02

    Aberrant DNA methylation seems to be associated with prostate cancer behavior. We investigated LINE-1 methylation in prostate cancer and non-neoplastic tissue adjacent to tumor (NTAT) in association with mortality from prostate cancer. We selected 157 prostate cancer patients with available NTAT from 2 cohorts of patients diagnosed between 1982-1988 and 1993-1996, followed up until 2010. An association between LINE-1 hypomethylation and prostate cancer mortality in tumor was suggested [hazard ratio per 5% decrease in LINE-1 methylation levels: 1.40, 95% confidence interval (CI): 0.95-2.01]. After stratification of the patients for Gleason score, the association was present only for those with a Gleason score of at least 8. Among these, low (<75%) vs. high (>80%) LINE-1 methylation was associated with a hazard ratio of 4.68 (95% CI: 1.03-21.34). LINE-1 methylation in the NTAT was not associated with prostate cancer mortality. Our results are consistent with the hypothesis that tumor tissue global hypomethylation may be a late event in prostate cancerogenesis and is associated with tumor progression.

  16. Helical antenna arrays for interstitial microwave thermal therapy for prostate cancer: tissue phantom testing and simulations for treatment

    NASA Astrophysics Data System (ADS)

    Sherar, Michael D.; Gladman, Aviv S.; Davidson, Sean R. H.; Trachtenberg, John; Gertner, Mark R.

    2001-07-01

    Interstitial microwave therapy is an experimental treatment for prostate cancer. The objective of this work was to measure the power deposition (specific absorption rate, SAR) patterns of helical microwave antennae both individually and in array patterns that would be useful for clinical treatment protocols. Commercial helical antenna 3D SAR patterns were measured in muscle equivalent phantoms using a thermographic technique. Two array patterns were tested: a `square' and a `crescent' array, both surrounding the urethra. To assess the feasibility of pre-treatment planning, the measured SAR patterns were input to a treatment planning computer simulation program based on a series of trans-rectal ultrasound images from a prostate cancer patient. The simulation solved the Pennes linear bioheat heat transfer equation in prostate tissue, with the aim of achieving a target of 55 °C at the prostate periphery while not allowing normal surrounding tissues (bladder, urethra, rectum) to rise above 42 °C. These criteria could not be met with the square array but they could be met with the crescent array, provided that the prostate was first dissected away from the rectum. This can be done with a procedure such as `hydrodissection', where sterile saline is injected to separate the prostate and rectum. The results of these SAR measurements and heat transfer simulations indicate that arrays of helical antennae could be used for safe and effective thermal therapy for prostate cancer.

  17. Dosimetric Coverage of the Prostate, Normal Tissue Sparing, and Acute Toxicity with High-Dose-Rate Brachytherapy for Large Prostate Volumes

    PubMed Central

    Yang, George; Strom, Tobin J.; Wilder, Richard B.; Shrinath, Kushagra; Mellon, Eric A.; Fernandez, Daniel C.; Biagioli, Matthew C.

    2015-01-01

    ABSTRACT Purpose To evaluate dosimetric coverage of the prostate, normal tissue sparing, and acute toxicity with HDR brachytherapy for large prostate volumes. Materials and Methods One hundred and two prostate cancer patients with prostate volumes >50 mL (range: 5-29 mL) were treated with high-dose-rate (HDR) brachytherapy ± intensity modulated radiation therapy (IMRT) to 4,500 cGy in 25 daily fractions between 2009 and 2013. HDR brachytherapy monotherapy doses consisted of two 1,350-1,400 cGy fractions separated by 2-3 weeks, and HDR brachytherapy boost doses consisted of two 950-1,150 cGy fractions separated by 4 weeks. Twelve of 32 (38%) unfavorable intermediate risk, high risk, and very high risk patients received androgen deprivation therapy. Acute toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4. Results Median follow-up was 14 months. Dosimetric goals were achieved in over 90% of cases. Three of 102 (3%) patients developed Grade 2 acute proctitis. No variables were significantly associated with Grade 2 acute proctitis. Seventeen of 102 (17%) patients developed Grade 2 acute urinary retention. American Urological Association (AUA) symptom score was the only variable significantly associated with Grade 2 acute urinary retention (p=0.04). There was no ≥ Grade 3 acute toxicity. Conclusions Dosimetric coverage of the prostate and normal tissue sparing were adequate in patients with prostate volumes >50 mL. Higher pre-treatment AUA symptom scores increased the relative risk of Grade 2 acute urinary retention. However, the overall incidence of acute toxicity was acceptable in patients with large prostate volumes. PMID:26200536

  18. Associations of Prostate-Specific Antigen, Prostate Carcinoma Tissue Gleason Score, and Androgen Receptor Expression with Bone Metastasis in Patients with Prostate Carcinoma.

    PubMed

    Chen, Yehui; Lin, Yun; Nie, Pin; Jiang, Wen; Liu, Yanqing; Yuan, Runqiang; Li, Miaoyuan; Zhao, Shijia; Lin, Huaxin; Li, Penghui; Zhang, Jinxiang; Hu, Zhiwen; Xu, Jin; Zhu, Xusheng

    2017-04-12

    BACKGROUND Prostate carcinoma (PCa) is often not diagnosed until advanced disease with bone metastasis. Predictive factors for bone metastasis are required to improve patient outcomes. The study aimed to analyze the factors associated with bone metastases in newly diagnosed patients with PCa. MATERIAL AND METHODS This was a retrospective study of 80 patients newly diagnosed with PCa by pathological examination between January 2012 and December 2014. Bone metastases were diagnosed by positron emission computed tomography. Clinical data, serological laboratory results, and pathological examination results were collected. RESULTS Among the 80 patients, 45 (56%) had bone metastases. Age, serum alkaline phosphatase, prostate-specific antigen (PSA), erythrocyte sedimentation rate, PCa tissue Gleason score, androgen receptor (AR) expression, and Ki-67 expression were higher in patients with bone metastasis compared with those without (all P<0.05). Multivariate logistic regression showed that PSA (OR: 1.005; 95%CI: 1.001-1.010; P=0.016), Gleason score (OR: 4.095; 95%CI: 1.592-10.529; P=0.003), and AR expression (OR: 14.023; 95%CI: 3.531-55.6981; P=0.005) were independently associated with bone metastases. Cut-off values for PSA, Gleason score, and AR expression were 67.1 ng/ml (sensitivity: 55.6%; specificity: 97.1%), 7.5 (sensitivity: 75.6%; specificity: 82.9%), and 2.5 (sensitivity: 84.0%; specificity: 91.4%), respectively. CONCLUSIONS PSA, Gleason score, and AR expression in PCa tissues were independently associated with PCa bone metastases. These results could help identifying patients with PCa at high risk of bone metastases.

  19. Analysis of the genetic phylogeny of multifocal prostate cancer identifies multiple independent clonal expansions in neoplastic and morphologically normal prostate tissue.

    PubMed

    Cooper, Colin S; Eeles, Rosalind; Wedge, David C; Van Loo, Peter; Gundem, Gunes; Alexandrov, Ludmil B; Kremeyer, Barbara; Butler, Adam; Lynch, Andrew G; Camacho, Niedzica; Massie, Charlie E; Kay, Jonathan; Luxton, Hayley J; Edwards, Sandra; Kote-Jarai, Zsofia; Dennis, Nening; Merson, Sue; Leongamornlert, Daniel; Zamora, Jorge; Corbishley, Cathy; Thomas, Sarah; Nik-Zainal, Serena; Ramakrishna, Manasa; O'Meara, Sarah; Matthews, Lucy; Clark, Jeremy; Hurst, Rachel; Mithen, Richard; Bristow, Robert G; Boutros, Paul C; Fraser, Michael; Cooke, Susanna; Raine, Keiran; Jones, David; Menzies, Andrew; Stebbings, Lucy; Hinton, Jon; Teague, Jon; McLaren, Stuart; Mudie, Laura; Hardy, Claire; Anderson, Elizabeth; Joseph, Olivia; Goody, Victoria; Robinson, Ben; Maddison, Mark; Gamble, Stephen; Greenman, Christopher; Berney, Dan; Hazell, Steven; Livni, Naomi; Fisher, Cyril; Ogden, Christopher; Kumar, Pardeep; Thompson, Alan; Woodhouse, Christopher; Nicol, David; Mayer, Erik; Dudderidge, Tim; Shah, Nimish C; Gnanapragasam, Vincent; Voet, Thierry; Campbell, Peter; Futreal, Andrew; Easton, Douglas; Warren, Anne Y; Foster, Christopher S; Stratton, Michael R; Whitaker, Hayley C; McDermott, Ultan; Brewer, Daniel S; Neal, David E

    2015-04-01

    Genome-wide DNA sequencing was used to decrypt the phylogeny of multiple samples from distinct areas of cancer and morphologically normal tissue taken from the prostates of three men. Mutations were present at high levels in morphologically normal tissue distant from the cancer, reflecting clonal expansions, and the underlying mutational processes at work in morphologically normal tissue were also at work in cancer. Our observations demonstrate the existence of ongoing abnormal mutational processes, consistent with field effects, underlying carcinogenesis. This mechanism gives rise to extensive branching evolution and cancer clone mixing, as exemplified by the coexistence of multiple cancer lineages harboring distinct ERG fusions within a single cancer nodule. Subsets of mutations were shared either by morphologically normal and malignant tissues or between different ERG lineages, indicating earlier or separate clonal cell expansions. Our observations inform on the origin of multifocal disease and have implications for prostate cancer therapy in individual cases.

  20. Analysis of the Genetic Phylogeny of Multifocal Prostate Cancer Identifies Multiple Independent Clonal Expansions in Neoplastic and Morphologically Normal Prostate Tissue

    PubMed Central

    Gundem, Gunes; Alexandrov, Ludmil B; Kremeyer, Barbara; Butler, Adam; Lynch, Andrew G; Camacho, Niedzica; Massie, Charlie E; Kay, Jonathan; Luxton, Hayley J; Edwards, Sandra; Kote-Jarai, ZSofia; Dennis, Nening; Merson, Sue; Leongamornlert, Daniel; Zamora, Jorge; Corbishley, Cathy; Thomas, Sarah; Nik-Zainal, Serena; O’Meara, Sarah; Matthews, Lucy; Clark, Jeremy; Hurst, Rachel; Mithen, Richard; Bristow, Robert G; Boutros, Paul C; Fraser, Michael; Cooke, Susanna; Raine, Keiran; Jones, David; Menzies, Andrew; Stebbings, Lucy; Hinton, Jon; Teague, Jon; McLaren, Stuart; Mudie, Laura; Hardy, Claire; Anderson, Elizabeth; Joseph, Olivia; Goody, Victoria; Robinson, Ben; Maddison, Mark; Gamble, Stephen; Greenman, Christopher; Berney, Dan; Hazell, Steven; Livni, Naomi; Fisher, Cyril; Ogden, Christopher; Kumar, Pardeep; Thompson, Alan; Woodhouse, Christopher; Nicol, David; Mayer, Erik; Dudderidge, Tim; Shah, Nimish C; Gnanapragasam, Vincent; Voet, Thierry; Campbell, Peter; Futreal, Andrew; Easton, Douglas; Stratton, Michael R

    2015-01-01

    Whole genome DNA sequencing was used to decrypt the phylogeny of multiple samples from distinct areas of cancer and morphologically normal tissue taken from the prostates of three men. Mutations were present at high levels in morphologically normal tissue distant from the cancer reflecting clonal expansions, and the underlying mutational processes at work in morphologically normal tissue were also at work in cancer. Our observations demonstrate the existence of on-going abnormal mutational processes, consistent with field-effects, underlying carcinogenesis. This mechanism gives rise to extensive branching evolution and cancer clone mixing as exemplified by the coexistence of multiple cancer lineages harboring distinct ERG fusions within a single cancer nodule. Subsets of mutations were shared either by morphologically normal and malignant tissue or between different ERG-lineages, indicating earlier or separate clonal cell expansions. Our observations inform on the origin of multifocal disease and have implications for prostate cancer therapy in individual cases. PMID:25730763

  1. Preliminary results on diode-laser assisted vaporization of prostate tissue

    NASA Astrophysics Data System (ADS)

    Sroka, Ronald; Seitz, Michael; Reich, Oliver; Bachmann, Alexander; Steinbrecher, Verena; Ackermann, Alexander; Stief, Christian

    2007-07-01

    Introduction and objectives: The aim was to identify the capability and the laser parameter of under water tissue vaporisation by means of a diode laser (1470 nm). Afterwards the feasibility and postoperative clinical outcome of vaporization of the prostate was investigated. Method: After acquiring suitable laser parameters in in-vitro experiments using a perfused tissue model patients (n=10) suffering from bladder outlet obstruction due to benign prostatic hyperplasia (BPH) were treated by diode laser. Their clinical outcome, in terms of acceptance and post-operatively voiding were evaluated. The diode laser emitted light of the wavelength of 1470 nm at 50 W (Biolitec GmbH) and delivered to the tissue by means of a side-fire fibre introduced through a 24F continuous-flow cystoscope. Normal saline was used for irrigation with an additive of 1% ethanol. The prostatic lobes (volume range 35-80ml) were vaporized within the prostatic capsular using sweeping and push and pull technique. The mean time of laser application was 2400 sec (1220-4000 sec) resulting in applied energies of 121 kJ in the mean (range: 61-200kJ). Results: During laser treatment none of the 10 patients showed any significant blood loss or any fluid absorption (no ethanol uptake). Foley catheters were removed between 18 and 168 hours postoperatively (mean: 49.8h+/-46h). After removal of the catheter the mean peak urine flow rate increased from 8.9ml/s +/- 2.9ml/s pre-operatively in comparison to 15.7ml/s +/- 5 ml/s (p=0.049) post-operatively. 8/10 patients were satisfied with their voiding outcome. None of the patients showed appearance of urgency, dysuria, hematuria, or incontinence but two patients required re-catheterization. After a follow-up of 1month, 8/10 patients showed evidence of good results and are satisfied with the outcome. Two patients required consecutive TUR-P. After a follow-up of 6-month the 8 patients are still satisfied. Conclusions: This very early and limited experience using

  2. Propionibacterium acnes inhibits FOXM1 and induces cell cycle alterations in human primary prostate cells.

    PubMed

    Sayanjali, Behnam; Christensen, Gitte J M; Al-Zeer, Munir A; Mollenkopf, Hans-Joachim; Meyer, Thomas F; Brüggemann, Holger

    2016-11-01

    Propionibacterium acnes has been detected in diseased human prostate tissue, and cell culture experiments suggest that the bacterium can establish a low-grade inflammation. Here, we investigated its impact on human primary prostate epithelial cells. Microarray analysis confirmed the inflammation-inducing capability of P. acnes but also showed deregulation of genes involved in the cell cycle. qPCR experiments showed that viable P. acnes downregulates a master regulator of cell cycle progression, FOXM1. Flow cytometry experiments revealed that P. acnes increases the number of cells in S-phase. We tested the hypothesis that a P. acnes-produced berninamycin-like thiopeptide is responsible for this effect, since it is related to the FOXM1 inhibitor siomycin. The thiopeptide biosynthesis gene cluster was strongly expressed; it is present in subtype IB of P. acnes, but absent from type IA, which is most abundant on human skin. A knock-out mutant lacking the gene encoding the berninamycin-like peptide precursor was unable to downregulate FOXM1 and to halt the cell cycle. Our study reveals a novel host cell-interacting activity of P. acnes.

  3. Expression of Voltage-Gated Sodium Channel Nav1.8 in Human Prostate Cancer is Associated with High Histological Grade

    PubMed Central

    Suy, Simeng; Hansen, Todd P.; Auto, Heather D.; Kallakury, Bhaskar V.S.; Dailey, Vernon; Danner, Malika; MacArthur, Linda; Zhang, Ying; Miessau, Matthew J.; Collins, Sean P.; Brown, Milton L.

    2013-01-01

    Voltage-gated sodium (Nav) channels are required for impulse conductance in excitable tissues. Navs have been linked to human cancers, including prostate. The expression and distribution of Nav isoforms (Nav1.1-Nav1.9) in human prostate cancer are not well established. Here, we evaluated the expression of these isoforms and investigated the expression of Nav1.8 in human prostate cancer tissues. Nav1.8 was highly expressed in all examined cells. Expression of Nav1.1, Nav1.2, and Nav1.9 were high in DU-145, PC-3 and PC-3M cells compared to LNCaP (hormone-dependent), C4-2, C4-2B, and CWR22Rv-1 cells. Nav1.5 and Nav1.6 were expressed in all cells examined. Nav1.7 expression was absent in PC-3M and CWR22Rv-1, but expressed in the other cells examined. Immunohistochemistry revealed intensive Nav1.8 staining correlated with more advanced pathologic stage of disease. Increased intensity of nuclear Nav1.8 correlated with increased Gleason grade. Our results revealed that Nav1.8 is universally expressed in human prostate cancer cells. Nav1.8 expression statistically correlated with pathologic stage (P=0.04) and Gleason score (P=0.01) of human prostate tissue specimens. The aberrant nuclear localization of Nav1.8 with advanced prostate cancer tissues warrant further investigation into use of Nav1.8 as a potential biomarker to differentiate between early and advanced disease. PMID:24163825

  4. Pyranocoumarin Tissue Distribution, Plasma Metabolome and Prostate Transcriptome Impacts of Sub-Chronic Exposure to Korean Angelica Supplement in Mice.

    PubMed

    Zhang, Jinhui; Li, Li; Tang, Suni; Zhang, Yong; Markiewski, Maciej; Xing, Chengguo; Jiang, Cheng; Lü, Junxuan

    2016-01-01

    Herbal products containing Korean Angelica gigas Nakai (AGN) root extract are marketed as dietary supplements for memory enhancement, pain killing, and female menopausal symptom relief. We have shown the anticancer activities of AGN supplements in mouse models. To facilitate human anticancer translational research, we characterized the tissue distribution of AGN marker pyranocoumarin compounds decursin (D) and decursinol angelate (DA) ([Formula: see text]% in AGN) and their metabolite decursinol (DOH), assessed the safety of sub-chronic AGN dietary exposure in mice, and explored its impact on plasma aqueous metabolites and the prostate transcriptome. The data show that after a gavage dose, plasma contained readily detectable DOH, but little D and DA, mirroring patterns in the liver. Extra-hepatic tissues retained greater levels of DA and D than the liver did. For sub-chronic exposures, male mice were provided ad libitum AIN93M-pellet diets with 0.5 and 1% AGN for six weeks. No adverse effects were observed on the plasma biochemistry markers of liver and kidney integrity in spite of their enlargement. Histopathological examinations of the liver, kidney and other visceral organs did not reveal tissue abnormalities. Metabolomic assessment of plasma from mice fed the 1%-AGN diet suggested metabolic shifts of key amino acids especially in the methionine-cysteine cycle, purine cycle, and glycolysis-citrate cycle. Prostate transcriptomic profiling identified gene signature changes in the metabolisms of drugs, lipids and cellular energetics, neuro-muscular features, immunity and inflammation, and tumor suppressor/oncogene balance. The safety profile was corroborated with a daily [Formula: see text] injection of AGN extract (100-300[Formula: see text]mg/kg) for four weeks, which resulted in much greater systemic pyranocoumarin exposure than the dietary route did.

  5. Reference-tissue correction of T2-weighted signal intensity for prostate cancer detection

    NASA Astrophysics Data System (ADS)

    Peng, Yahui; Jiang, Yulei; Oto, Aytekin

    2014-03-01

    The purpose of this study was to investigate whether correction with respect to reference tissue of T2-weighted MRimage signal intensity (SI) improves its effectiveness for classification of regions of interest (ROIs) as prostate cancer (PCa) or normal prostatic tissue. Two image datasets collected retrospectively were used in this study: 71 cases acquired with GE scanners (dataset A), and 59 cases acquired with Philips scanners (dataset B). Through a consensus histology- MR correlation review, 175 PCa and 108 normal-tissue ROIs were identified and drawn manually. Reference-tissue ROIs were selected in each case from the levator ani muscle, urinary bladder, and pubic bone. T2-weighted image SI was corrected as the ratio of the average T2-weighted image SI within an ROI to that of a reference-tissue ROI. Area under the receiver operating characteristic curve (AUC) was used to evaluate the effectiveness of T2-weighted image SIs for differentiation of PCa from normal-tissue ROIs. AUC (+/- standard error) for uncorrected T2-weighted image SIs was 0.78+/-0.04 (datasets A) and 0.65+/-0.05 (datasets B). AUC for corrected T2-weighted image SIs with respect to muscle, bladder, and bone reference was 0.77+/-0.04 (p=1.0), 0.77+/-0.04 (p=1.0), and 0.75+/-0.04 (p=0.8), respectively, for dataset A; and 0.81+/-0.04 (p=0.002), 0.78+/-0.04 (p<0.001), and 0.79+/-0.04 (p<0.001), respectively, for dataset B. Correction in reference to the levator ani muscle yielded the most consistent results between GE and Phillips images. Correction of T2-weighted image SI in reference to three types of extra-prostatic tissue can improve its effectiveness for differentiation of PCa from normal-tissue ROIs, and correction in reference to the levator ani muscle produces consistent T2-weighted image SIs between GE and Phillips MR images.

  6. Angiostatic Therapy: A New Treatment Modality for Prostate Cancer

    DTIC Science & Technology

    2001-07-01

    could be a new innovative treatment regimen for hormone-refractory prostate cancer. This was to be achieved with human prostate cancer tissue and...indices, low cell death and a highly invasive phenotype. Using this model we identified surgical castration, COX-2 inhibition and dendritic cell based immunotherapy as effective mono and combined therapies for prostate carcinoma.

  7. Genome-wide analysis of AR binding and comparison with transcript expression in primary human fetal prostate fibroblasts and cancer associated fibroblasts.

    PubMed

    Nash, Claire; Boufaied, Nadia; Mills, Ian G; Franco, Omar E; Hayward, Simon W; Thomson, Axel A

    2017-05-05

    The androgen receptor (AR) is a transcription factor, and key regulator of prostate development and cancer, which has discrete functions in stromal versus epithelial cells. AR expressed in mesenchyme is necessary and sufficient for prostate development while loss of stromal AR is predictive of prostate cancer progression. Many studies have characterized genome-wide binding of AR in prostate tumour cells but none have used primary mesenchyme or stroma. We applied ChIPseq to identify genomic AR binding sites in primary human fetal prostate fibroblasts and patient derived cancer associated fibroblasts, as well as the WPMY1 cell line overexpressing AR. We identified AR binding sites that were specific to fetal prostate fibroblasts (7534), cancer fibroblasts (629), WPMY1-AR (2561) as well as those common among all (783). Primary fibroblasts had a distinct AR binding profile versus prostate cancer cell lines and tissue, and showed a localisation to gene promoter binding sites 1 kb upstream of the transcriptional start site, as well as non-classical AR binding sequence motifs. We used RNAseq to define transcribed genes associated with AR binding sites and derived cistromes for embryonic and cancer fibroblasts as well as a cistrome common to both. These were compared to several in vivo ChIPseq and transcript expression datasets; which identified subsets of AR targets that were expressed in vivo and regulated by androgens. This analysis enabled us to deconvolute stromal AR targets active in stroma within tumour samples. Taken together, our data suggest that the AR shows significantly different genomic binding site locations in primary prostate fibroblasts compared to that observed in tumour cells. Validation of our AR binding site data with transcript expression in vitro and in vivo suggests that the AR target genes we have identified in primary fibroblasts may contribute to clinically significant and biologically important AR-regulated changes in prostate tissue

  8. Inhibition of prostate cancer metastasis by administration of a tissue vaccine.

    PubMed

    Suckow, Mark A; Wolter, William R; Sailes, Valerie T

    2008-01-01

    Immunotherapy by vaccination represents a novel method for treatment of cancer. In this regard, vaccines with the broadest possible menu of relevant antigens stand the greatest chance of success. Tissue vaccines are composed of material harvested directly from tumors and contain not only antigens associated with neoplastic epithelium, but also those that may be unique to in vivo growth and antigens associated with the tumor stroma. To test the hypothesis that a tissue vaccine, produced by glutaraldehyde fixation of harvested syngeneic prostate tumors (GFT vaccine), could be used for treatment of prostate cancer, male Lobund-Wistar (LW) rats were treated with methylnitrosourea (MNU) and testosterone propionate to induce autochthonous prostate tumors. Tumor-bearing rats were randomly assigned to one of three treatment groups: no treatment (11 rats); vaccination with media (10 rats); or vaccination with the GFT vaccine (19 rats). Vaccination was given initially with Freund's complete adjuvant and booster doses were given with incomplete Freund's adjuvant every week until the time of euthanasia. There were no significant differences in mean tumor weight between groups; however, GFT-vaccinated rats had a prolonged survival time; and 4/19 (21%) GFT-vaccinated rats were found to be tumor-free compared to none of the untreated or media-treated controls. Further, pulmonary metastasis occurred in only 5/15 (33%) of GFT-vaccinated rats compared to 10/11 (91%) and 10/10 (100%) of untreated and media-vaccinated controls, respectively. Supernatants of cultured splenocytes from similarly media- and GFT-vaccinated rats demonstrated significant (P < 0.001) increases in IFN-gamma and TNF-alpha from splenocytes of GFT-vaccinated rats, suggesting that GFT vaccination stimulates a Th1 response. In summary, treatment of tumor-bearing rats with a tissue vaccine stimulated a protective immune response that resulted in complete tumor regression in 21% of animals and reduced the number of

  9. Human histocultures (tissue explants) in retrovirology

    PubMed Central

    Arakelyan, Anush; Fitzgerald, Wendy; Grivel, Jean-Charles; Vanpouille, Christophe; Margolis, Leonid

    2014-01-01

    Summary Viral pathogenesis is studied predominantly in cultures of primary isolated cells or cell lines. Many retroviruses efficiently replicate only in activated cells. Therefore, in order to become efficient viral producers cells should be artificially activated, a procedure which significantly changes cell physiology. However, for many viral diseases, like HIV-1 and other retroviruses’ diseases, critical pathogenic events occur in tissues and cell isolation from their native microenvironment prevents single cell cultures from faithfully reflecting important aspects of cell-cell and cell-pathogen interactions that occur in the context of complex tissue cytoarchitecture. Tissue explants (histocultures) that retain tissue cytoarchitecture and many aspects of cell-cell interactions more faithfully represent in vivo tissue features. Human histocultures constitute an adequate model for studying viral pathogenesis under controlled laboratory conditions. Protocols for various human histocultures as applied to study retroviral pathogenesis, in particular of HIV-1, have been refined by our laboratory and are described in the present publication. Human histocultures of human tonsils and lymph nodes, as well as of recto-sigmoid and cervico-vaginal tissues can be used to study viral transmission, pathogenesis and as a pre-clinical platform for antivirals evaluation. PMID:24158827

  10. Molecular effects of soy phytoalexin glyceollins in human prostate cancer cells LNCaP

    USDA-ARS?s Scientific Manuscript database

    Glyceollins are soy–derived phytoalexins that have been proposed to be candidate cancer preventive compounds. The effect of the glyceollins on prostate cancer is unknown. The present study examined the molecular effects of soy phytoalexins, glyceollins, on the human prostate cancer cell line LNCaP t...

  11. MRS measured fatty acid composition of periprostatic adipose tissue correlates with pathological measures of prostate cancer aggressiveness.

    PubMed

    Iordanescu, Gheorghe; Brendler, Charles; Crawford, Susan E; Wyrwicz, Alice M; Venkatasubramanian, Palamadai N; Doll, Jennifer A

    2015-09-01

    To investigate the association between magnetic resonance (MR) spectroscopically measured fatty acid composition of periprostatic adipose tissue and pathological markers of prostate cancer aggressiveness. Periprostatic adipose (PPA) and subcutaneous adipose (SQA) tissue from prostate cancer patients undergoing radical prostatectomy were examined ex vivo by proton MR spectroscopy at 14.1T (n = 31). Fractions of monounsaturated, polyunsaturated, total unsaturated, and saturated fatty acids, as well as T2 relaxation times were measured from the spectra. Univariate and multivariate analyses based on receiver operating characteristic (ROC) and support vector machines (SVM) were used to evaluate the association between differential measures of fatty acid levels in the PPA and SQA tissues and Gleason score and extracapsular extension (ECE), which are pathological measures of prostate cancer aggressiveness. Both pathological markers for aggressive prostate cancer have separable patterns in the MRS features space. The association between ECE and PPA tissue fatty acid composition is linear (area under receiver operating characteristic curve (AROC) and 95% confidence intervals [CIs]: 1.00, [1.00, 1.00]), along the Δ(fM /fS ) measure, and is marked by elevated monounsaturated and reduced saturated fatty acids in the PPA tissue relative to SQA. In contrast, the association between Gleason score and PPA tissue fatty acid composition is nonlinear (classifier AROC and 95% CIs: 0.86, [0.71, 1.00]). Fatty acid composition is altered in the PPA tissue of patients with aggressive prostate cancer. Ex vivo MR spectroscopy may be a useful tool in studying the altered fatty acid metabolism in prostate cancer. © 2014 Wiley Periodicals, Inc.

  12. Does Inflammation Mediate the Obesity and BPH Relationship? An Epidemiologic Analysis of Body Composition and Inflammatory Markers in Blood, Urine, and Prostate Tissue, and the Relationship with Prostate Enlargement and Lower Urinary Tract Symptoms.

    PubMed

    Fowke, Jay H; Koyama, Tatsuki; Fadare, Oluwole; Clark, Peter E

    2016-01-01

    BPH is a common disease associated with age and obesity. However, the biological pathways between obesity and BPH are unknown. Our objective was to investigate biomarkers of systemic and prostate tissue inflammation as potential mediators of the obesity and BPH association. Participants included 191 men without prostate cancer at prostate biopsy. Trained staff measured weight, height, waist and hip circumferences, and body composition by bioelectric impedance analysis. Systemic inflammation was estimated by serum IL-6, IL-1β, IL-8, and TNF-α; and by urinary prostaglandin E2 metabolite (PGE-M), F2-isoprostane (F2iP), and F2-isoprostane metabolite (F2iP-M) levels. Prostate tissue was scored for grade, aggressiveness, extent, and location of inflammatory regions, and also stained for CD3 and CD20 positive lymphocytes. Analyses investigated the association between multiple body composition scales, systemic inflammation, and prostate tissue inflammation against BPH outcomes, including prostate size at ultrasound and LUTS severity by the AUA-symptom index (AUA-SI). Prostate size was significantly associated with all obesity measures. For example, prostate volume was 5.5 to 9.0 mls larger comparing men in the 25th vs. 75th percentile of % body fat, fat mass (kg) or lean mass (kg). However, prostate size was not associated with proinflammatory cytokines, PGE-M, F2iP, F2iP-M, prostate tissue inflammation scores or immune cell infiltration. In contrast, the severity of prostate tissue inflammation was significantly associated with LUTS, such that there was a 7 point difference in AUA-SI between men with mild vs. severe inflammation (p = 0.004). Additionally, men with a greater waist-hip ratio (WHR) were significantly more likely to have severe prostate tissue inflammation (p = 0.02), and a high WHR was significantly associated with moderate/severe LUTS (OR = 2.56, p = 0.03) among those participants with prostate tissue inflammation. The WHR, an estimate of centralized

  13. Does Inflammation Mediate the Obesity and BPH Relationship? An Epidemiologic Analysis of Body Composition and Inflammatory Markers in Blood, Urine, and Prostate Tissue, and the Relationship with Prostate Enlargement and Lower Urinary Tract Symptoms

    PubMed Central

    Fowke, Jay H.; Koyama, Tatsuki; Fadare, Oluwole; Clark, Peter E.

    2016-01-01

    Background BPH is a common disease associated with age and obesity. However, the biological pathways between obesity and BPH are unknown. Our objective was to investigate biomarkers of systemic and prostate tissue inflammation as potential mediators of the obesity and BPH association. Methods Participants included 191 men without prostate cancer at prostate biopsy. Trained staff measured weight, height, waist and hip circumferences, and body composition by bioelectric impedance analysis. Systemic inflammation was estimated by serum IL-6, IL-1β, IL-8, and TNF-α; and by urinary prostaglandin E2 metabolite (PGE-M), F2-isoprostane (F2iP), and F2-isoprostane metabolite (F2iP-M) levels. Prostate tissue was scored for grade, aggressiveness, extent, and location of inflammatory regions, and also stained for CD3 and CD20 positive lymphocytes. Analyses investigated the association between multiple body composition scales, systemic inflammation, and prostate tissue inflammation against BPH outcomes, including prostate size at ultrasound and LUTS severity by the AUA-symptom index (AUA-SI). Results Prostate size was significantly associated with all obesity measures. For example, prostate volume was 5.5 to 9.0 mls larger comparing men in the 25th vs. 75th percentile of % body fat, fat mass (kg) or lean mass (kg). However, prostate size was not associated with proinflammatory cytokines, PGE-M, F2iP, F2iP-M, prostate tissue inflammation scores or immune cell infiltration. In contrast, the severity of prostate tissue inflammation was significantly associated with LUTS, such that there was a 7 point difference in AUA-SI between men with mild vs. severe inflammation (p = 0.004). Additionally, men with a greater waist-hip ratio (WHR) were significantly more likely to have severe prostate tissue inflammation (p = 0.02), and a high WHR was significantly associated with moderate/severe LUTS (OR = 2.56, p = 0.03) among those participants with prostate tissue inflammation. Conclusion

  14. Evaluating Baculovirus as a Vector for Human Prostate Cancer Gene Therapy

    PubMed Central

    Swift, Stephanie L.; Rivera, Guillermo C.; Dussupt, Vincent; Leadley, Regina M.; Hudson, Lucy C.; MA de Ridder, Corrina; Kraaij, Robert; Burns, Julie E.; Maitland, Norman J.; Georgopoulos, Lindsay J.

    2013-01-01

    Gene therapy represents an attractive strategy for the non-invasive treatment of prostate cancer, where current clinical interventions show limited efficacy. Here, we evaluate the use of the insect virus, baculovirus (BV), as a novel vector for human prostate cancer gene therapy. Since prostate tumours represent a heterogeneous environment, a therapeutic approach that achieves long-term regression must be capable of targeting multiple transformed cell populations. Furthermore, discrimination in the targeting of malignant compared to non-malignant cells would have value in minimising side effects. We employed a number of prostate cancer models to analyse the potential for BV to achieve these goals. In vitro, both traditional prostate cell lines as well as primary epithelial or stromal cells derived from patient prostate biopsies, in two- or three-dimensional cultures, were used. We also evaluated BV in vivo in murine prostate cancer xenograft models. BV was capable of preferentially transducing invasive malignant prostate cancer cell lines compared to early stage cancers and non-malignant samples, a restriction that was not a function of nuclear import. Of more clinical relevance, primary patient-derived prostate cancer cells were also efficiently transduced by BV, with robust rates observed in epithelial cells of basal phenotype, which expressed BV-encoded transgenes faster than epithelial cells of a more differentiated, luminal phenotype. Maximum transduction capacity was observed in stromal cells. BV was able to penetrate through three-dimensional structures, including in vitro spheroids and in vivo orthotopic xenografts. BV vectors containing a nitroreductase transgene in a gene-directed enzyme pro-drug therapy approach were capable of efficiently killing malignant prostate targets following administration of the pro-drug, CB1954. Thus, BV is capable of transducing a large proportion of prostate cell types within a heterogeneous 3-D prostate tumour, can

  15. The comparative evaluation of apoptosis produced by leuprolide or orchiectomy on rat prostate tissue.

    PubMed

    Cakiroglu, Basri; Hazar, Aydin Ismet; Eyyupoglu, Seyit Erkan; Can Balci, Mustafa Bahadir; Sinanoglu, Orhun; Tuzlali, Pinar

    2016-01-14

    Organisms are constantly in a balance meaning that while new cells are produced, some of the older ones die which takes place in 2 ways: necrosis or apoptosis. Apoptosis is the programmed cellular death triggered by intrinsic or extrinsic stimuli. In this study we have evaluated the apoptosis of prostate tissue generated by surgical or medical orchiectomy. In this experimental study, we used 36 adult male rats that were evaluated in 3 groups. The first group (Group 1) consisted of 12 rats that had bilateral orchiectomy; the second group (Group 2) included 12 rats that were given leuprolide acetate and the third group (Group 3) consisted of 12 control rats. Immunohistochemical staining of the prostate of all rats was performed and the presence of glandular atrophy and apoptosis were evaluated in the three groups. The statistical differences between the two groups were evaluated by the Fisher exact test. Glandular atrophy was not determined in any rat of the control group, and the apoptotic staining was in the normal limits in all the control rats. In Leuprolide group, glandular atrophy was mild in 7 cases, and moderate in 3 rats. In 2 rats of the Leuprolide group, atrophy was not demonstrated. In surgical orchiectomy group, glandular atrophy was present in all cases. Atrophy was observed as cystic atrophy. Statistical analysis with the Fisher exact test revealed that glandular atrophy was statistically significantly more common in surgical orchiectomy group compared with Leuprolide group (p = 0,012). If the aim of treatment in androgen dependent prostatic adenocarcinoma or benign prostate hypertrophy is the construction of a robust apoptosis, bilateral orchiectomy generates a more powerful apoptosis compared with Leuprolide.

  16. Performance assessment of automated tissue characterization for prostate H and E stained histopathology

    NASA Astrophysics Data System (ADS)

    DiFranco, Matthew D.; Reynolds, Hayley M.; Mitchell, Catherine; Williams, Scott; Allan, Prue; Haworth, Annette

    2015-03-01

    Reliable automated prostate tumor detection and characterization in whole-mount histology images is sought in many applications, including post-resection tumor staging and as ground-truth data for multi-parametric MRI interpretation. In this study, an ensemble-based supervised classification algorithm for high-resolution histology images was trained on tile-based image features including histogram and gray-level co-occurrence statistics. The algorithm was assessed using different combinations of H and E prostate slides from two separate medical centers and at two different magnifications (400x and 200x), with the aim of applying tumor classification models to new data. Slides from both datasets were annotated by expert pathologists in order to identify homogeneous cancerous and non-cancerous tissue regions of interest, which were then categorized as (1) low-grade tumor (LG-PCa), including Gleason 3 and high-grade prostatic intraepithelial neoplasia (HG-PIN), (2) high-grade tumor (HG-PCa), including various Gleason 4 and 5 patterns, or (3) non-cancerous, including benign stroma and benign prostatic hyperplasia (BPH). Classification models for both LG-PCa and HG-PCa were separately trained using a support vector machine (SVM) approach, and per-tile tumor prediction maps were generated from the resulting ensembles. Results showed high sensitivity for predicting HG-PCa with an AUC up to 0.822 using training data from both medical centres, while LG-PCa showed a lower sensitivity of 0.763 with the same training data. Visual inspection of cancer probability heatmaps from 9 patients showed that 17/19 tumors were detected, and HG-PCa generally reported less false positives than LG-PCa.

  17. Differential levels of human leukocyte antigen-class I, multidrug-resistance 1 and androgen receptor expressions in untreated prostate cancer cells: the robustness of prostate cancer.

    PubMed

    Homma, Shigenori; Komohara, Yoshihiro; Harada, Mamoru; Saya, Hideyuki; Todo, Satoru; Itoh, Kyogo; Noguchi, Masanori

    2007-08-01

    Tumors are highly robust and maintain their proliferative potential against a wide range of both host-defense mechanisms and anticancer therapies. One of the approaches to overcome cancer robustness could be combined therapy in which each modality imposes independent selective pressures against the acquired mutation of cancer. To develop such a therapy, it is crucial to understand the magnitude of acquired mutations. In this study, we investigated the levels of human leukocyte antigen (HLA)-class I, multidrug-resistance 1 (MDR1), and androgen receptor (AR) expressions in untreated prostate cancers harvested by radical prostatectomy. The mean percentages of cancer cells expressing HLA-class I, MDR and AR among the 10 cancer samples were 41, 35 and 74%, respectively. In addition, double-staining of HLA and MDR revealed the four definite populations (HLA+/MDR+, HLA+/MDR-, HLA-/MDR+ and HLA-/MDR-) in cancer tissues from the majority of cancer patients tested, and the mean percentages of cells expressing these combinations were 13, 29, 22 and 38%, respectively. Similar results were obtained by double-staining of HLA and AR, except for 2 cases in which HLA-/AR+ cancer cells predominated. These results indicated that untreated prostate cancer cells acquired a wide range of genomic mutations, which may have been caused by internal host pressure to eliminate malignant cells, and would provide evidence of the robustness of untreated prostate cancer.

  18. Accumulation of perfluoroalkyl substances in human tissues.

    PubMed

    Pérez, Francisca; Nadal, Martí; Navarro-Ortega, Alícia; Fàbrega, Francesc; Domingo, José L; Barceló, Damià; Farré, Marinella

    2013-09-01

    Perfluoroalkyl substances (PFASs) are environmental pollutants with an important bioaccumulation potential. However, their metabolism and distribution in humans are not well studied. In this study, the concentrations of 21 PFASs were analyzed in 99 samples of autopsy tissues (brain, liver, lung, bone, and kidney) from subjects who had been living in Tarragona (Catalonia, Spain). The samples were analyzed by solvent extraction and online purification by turbulent flow and liquid chromatography coupled to tandem mass spectrometry. The occurrence of PFASs was confirmed in all human tissues. Although PFASs accumulation followed particular trends depending on the specific tissue, some similarities were found. In kidney and lung, perfluorobutanoic acid was the most frequent compound, and at highest concentrations (median values: 263 and 807ng/g in kidney and lung, respectively). In liver and brain, perfluorohexanoic acid showed the maximum levels (median: 68.3 and 141ng/g, respectively), while perfluorooctanoic acid was the most contributively in bone (median: 20.9ng/g). Lung tissues accumulated the highest concentration of PFASs. However, perfluorooctane sulfonic acid and perfluorooctanoic acid were more prevalent in liver and bone, respectively. To the best of our knowledge, the accumulation of different PFASs in samples of various human tissues from the same subjects is here reported for the very first time. The current results may be of high importance for the validation of physiologically based pharmacokinetic models, which are being developed for humans. However, further studies on the distribution of the same compounds in the human body are still required.

  19. Effects of a human plasma membrane-associated sialidase siRNA on prostate cancer invasion

    SciTech Connect

    Li, Xiaojie; Zhang, Ling; Shao, Yueting; Liang, Zuowen; Shao, Chen; Wang, Bo; Guo, Baofeng; Li, Na; Zhao, Xuejian; Li, Yang; Xu, Deqi

    2011-12-16

    Highlights: Black-Right-Pointing-Pointer Neu3 is as one of the sialidases and regulates cell surface functions. Black-Right-Pointing-Pointer A Neu3-specific siRNA inhibited prostrate cancer cell invasion and migration. Black-Right-Pointing-Pointer The Neu3-specific siRNA inhibited prostate cancer metastasis in mice. Black-Right-Pointing-Pointer Targeting Neu3 may have utility for gene-based therapy of human cancer metastasis. -- Abstract: Human plasma membrane-associated sialidase (Neu3) is one of several sialidases that hydrolyze sialic acids in the terminal position of the carbohydrate groups of glycolipids and glycoproteins. Neu3 is mainly localized in plasma membranes and plays crucial roles in the regulation of cell surface functions. In this study, we investigated the effects and molecular mechanisms of Neu3 on cell invasion and migration in vivo and in vitro. Initially, we found that the levels of Neu3 expression were higher in prostate cancer tissues and cell lines than in normal prostate tissues based on RT-PCR and Western blotting analyses. We then applied a Neu3 siRNA approach to block Neu3 signaling using PC-3M cells as model cells. Transwell invasion assays and wound assays showed significantly decreased invasion and migration potential in the Neu3 siRNA-transfected cells. RT-PCR and Western blotting analyses revealed that Neu3 knockdown decreased the expressions of the matrix metalloproteinases MMP-2 and MMP-9. In vivo, mice injected with PC-3M cell tumors were evaluated by SPECT/CT to determine the presence of bone metastases. Mice treated with attenuated Salmonella carrying the Neu3 siRNA developed fewer bone metastases than mice treated with attenuated Salmonella carrying a control Scramble siRNA, attenuated Salmonella alone or PBS. The results for bone metastasis detection by pathology were consistent with the data obtained by SPECT/CT. Tumor blocks were evaluated by histochemical, RT-PCR and Western blotting analyses. The results revealed

  20. miR-409-3p/-5p promotes tumorigenesis, epithelial to mesenchymal transition and bone metastasis of human prostate cancer

    PubMed Central

    Josson, Sajni; Gururajan, Murali; Hu, Peizhen; Shao, Chen; Chu, Gina Chia-Yi; Zhau, Haiyen E.; Liu, Chunyan; Lao, Kaiqin; Lu, Chia-Lun; Lu, Yi-Tsung; Lichterman, Jake; Nandana, Srinivas; Li, Quanlin; Rogatko, Andre; Berel, Dror; Posadas, Edwin M.; Fazli, Ladan; Sareen, Dhruv; Chung, Leland W. K.

    2014-01-01

    Purpose miR-409-3p/-5p is a microRNA expressed by embryonic stem cells and its role in cancer biology and metastasis is unknown. Our pilot studies demonstrated elevated miR-409-3p/-5p expression in human prostate cancer bone metastatic cell lines, therefore we defined the biological impact of manipulation of miR-409-3p/-5p in prostate cancer progression and correlated the levels of its expression with clinical human prostate cancer bone metastatic specimens. Experimental Design miRNA profiling of prostate cancer bone metastatic EMT cell line model was performed. Gleason score human tissue array was probed for validation of specific miRNAs. Additionally, genetic manipulation of miR-409-3p/-5p was performed to determine its role in tumor growth, epithelial to mesenchymal transition (EMT) and bone metastasis in mouse models. Results Elevated expression of miR-409-3p/-5p was observed in bone metastatic prostate cancer cell lines and human prostate cancer tissues with higher Gleason scores. Elevated miR-409-3p expression levels correlated with prostate cancer patient progression free survival. Orthotopic delivery of miR-409-3p/-5p in the murine prostate gland induced tumors where the tumors expressed, EMT and stemness markers. Intracardiac inoculation (to mimic systemic dissemination) of miR-409-5p inhibitor treated bone metastatic ARCaPM prostate cancer cells in mice, led to decreased bone metastasis and increased survival compared to control vehicle-treated cells. Conclusion miR-409-3p/-5p plays an important role in prostate cancer biology by facilitating tumor growth, EMT and bone metastasis. This finding bear’s particular translational importance since miR-409-3p/-5p appears to be an attractive biomarker and/or possibly a therapeutic target to treat bones metastatic prostate cancer. PMID:24963047

  1. Prediction of alpha1-adrenoceptor occupancy in the human prostate from plasma concentrations of silodosin, tamsulosin and terazosin to treat urinary obstruction in benign prostatic hyperplasia.

    PubMed

    Yamada, Shizuo; Kato, Yasuhiro; Okura, Takashi; Kagawa, Yoshiyuki; Kawabe, Kazuki

    2007-07-01

    Alpha1-adrenoceptor antagonists are clinically useful for the improvement of urinary obstruction due to benign prostatic hyperplasia (BPH), and their therapeutic effects are mediated through the blockade of prostatic alpha(1)-adrenoceptors. The present study was undertaken to predict the magnitude and duration of alpha(1)-adrenoceptor occupancy in the human prostate after oral alpha(1)-adrenoceptor antagonists. Prostatic alpha(1)-adrenoceptor-binding parameters of silodosin were estimated by measuring specific [(3)H]prazosin binding in rat prostate after oral administration of this drug. The plasma concentration of silodosin after oral administration in rats and healthy volunteers was measured using a high-performance liquid chromatographic method. The alpha(1)-adrenoceptor-binding affinities (K(i)) of silodosin, tamsulosin, and terazosin in the human prostate and plasma concentrations of tamsulosin and terazosin were obtained from the literature. Using the alpha(1)-adrenoceptor binding parameters of silodosin in rat prostate, alpha(1)-adrenoceptor occupancy in the human prostate was estimated to be around 60-70% at 1-6 h after oral administration of silodosin at doses of 3.0, 8.1, and 16.1 micromol. Thereafter, the receptor occupancy was periodically decreased, to 24% (8.1 micromol) and 54% (16.1 micromol) 24 h later. A similar magnitude and time course of alpha(1)-adrenoceptor occupancy by silodosin in the human prostate were estimated using alpha(1)-adrenoceptor-binding affinities (K(i)) in the human prostate. Despite about two orders of differences in the plasma unbound concentrations after clinically effective oral dosages of silodosin, tamsulosin, and terazosin, there was a comparable magnitude of prostatic alpha(1)-adrenoceptor occupancy by these drugs. In conclusion, the prediction of alpha(1)-adrenoceptor occupancy in the human prostate by alpha(1)-adrenoceptor antagonists may provide the rationale for the optimum dosage regimen of these drugs in the

  2. Prostate field cancerization: deregulated expression of macrophage inhibitory cytokine 1 (MIC-1) and platelet derived growth factor A (PDGF-A) in tumor adjacent tissue.

    PubMed

    Jones, Anna C; Antillon, Kresta S; Jenkins, Shannon M; Janos, Sara N; Overton, Heidi N; Shoshan, Dor S; Fischer, Edgar G; Trujillo, Kristina A; Bisoffi, Marco

    2015-01-01

    Prostate field cancerization denotes molecular alterations in histologically normal tissues adjacent to tumors. Such alterations include deregulated protein expression, as we have previously shown for the key transcription factor early growth response 1 (EGR-1) and the lipogenic enzyme fatty acid synthase (FAS). Here we add the two secreted factors macrophage inhibitory cytokine 1 (MIC-1) and platelet derived growth factor A (PDGF-A) to the growing list of protein markers of prostate field cancerization. Expression of MIC-1 and PDGF-A was measured quantitatively by immunofluorescence and comprehensively analyzed using two methods of signal capture and several groupings of data generated in human cancerous (n = 25), histologically normal adjacent (n = 22), and disease-free (n = 6) prostate tissues. A total of 208 digitized images were analyzed. MIC-1 and PDGF-A expression in tumor tissues were elevated 7.1x to 23.4x and 1.7x to 3.7x compared to disease-free tissues, respectively (p<0.0001 to p = 0.08 and p<0.01 to p = 0.23, respectively). In support of field cancerization, MIC-1 and PDGF-A expression in adjacent tissues were elevated 7.4x to 38.4x and 1.4x to 2.7x, respectively (p<0.0001 to p<0.05 and p<0.05 to p = 0.51, respectively). Also, MIC-1 and PDGF-A expression were similar in tumor and adjacent tissues (0.3x to 1.0x; p<0.001 to p = 0.98 for MIC-1; 0.9x to 2.6x; p<0.01 to p = 1.00 for PDGF-A). All analyses indicated a high level of inter- and intra-tissue heterogeneity across all types of tissues (mean coefficient of variation of 86.0%). Our data shows that MIC-1 and PDGF-A expression is elevated in both prostate tumors and structurally intact adjacent tissues when compared to disease-free specimens, defining field cancerization. These secreted factors could promote tumorigenesis in histologically normal tissues and lead to tumor multifocality. Among several clinical applications, they could also be exploited as indicators of disease in false negative

  3. Prostate Field Cancerization: Deregulated Expression of Macrophage Inhibitory Cytokine 1 (MIC-1) and Platelet Derived Growth Factor A (PDGF-A) in Tumor Adjacent Tissue

    PubMed Central

    Jones, Anna C.; Shoshan, Dor S.; Fischer, Edgar G.; Trujillo, Kristina A.; Bisoffi, Marco

    2015-01-01

    Prostate field cancerization denotes molecular alterations in histologically normal tissues adjacent to tumors. Such alterations include deregulated protein expression, as we have previously shown for the key transcription factor early growth response 1 (EGR-1) and the lipogenic enzyme fatty acid synthase (FAS). Here we add the two secreted factors macrophage inhibitory cytokine 1 (MIC-1) and platelet derived growth factor A (PDGF-A) to the growing list of protein markers of prostate field cancerization. Expression of MIC-1 and PDGF-A was measured quantitatively by immunofluorescence and comprehensively analyzed using two methods of signal capture and several groupings of data generated in human cancerous (n = 25), histologically normal adjacent (n = 22), and disease-free (n = 6) prostate tissues. A total of 208 digitized images were analyzed. MIC-1 and PDGF-A expression in tumor tissues were elevated 7.1x to 23.4x and 1.7x to 3.7x compared to disease-free tissues, respectively (p<0.0001 to p = 0.08 and p<0.01 to p = 0.23, respectively). In support of field cancerization, MIC-1 and PDGF-A expression in adjacent tissues were elevated 7.4x to 38.4x and 1.4x to 2.7x, respectively (p<0.0001 to p<0.05 and p<0.05 to p = 0.51, respectively). Also, MIC-1 and PDGF-A expression were similar in tumor and adjacent tissues (0.3x to 1.0x; p<0.001 to p = 0.98 for MIC-1; 0.9x to 2.6x; p<0.01 to p = 1.00 for PDGF-A). All analyses indicated a high level of inter- and intra-tissue heterogeneity across all types of tissues (mean coefficient of variation of 86.0%). Our data shows that MIC-1 and PDGF-A expression is elevated in both prostate tumors and structurally intact adjacent tissues when compared to disease-free specimens, defining field cancerization. These secreted factors could promote tumorigenesis in histologically normal tissues and lead to tumor multifocality. Among several clinical applications, they could also be exploited as indicators of disease in false negative

  4. Humanized mice with ectopic artificial liver tissues.

    PubMed

    Chen, Alice A; Thomas, David K; Ong, Luvena L; Schwartz, Robert E; Golub, Todd R; Bhatia, Sangeeta N

    2011-07-19

    "Humanized" mice offer a window into aspects of human physiology that are otherwise inaccessible. The best available methods for liver humanization rely on cell transplantation into immunodeficient mice with liver injury but these methods have not gained widespread use due to the duration and variability of hepatocyte repopulation. In light of the significant progress that has been achieved in clinical cell transplantation through tissue engineering, we sought to develop a humanized mouse model based on the facile and ectopic implantation of a tissue-engineered human liver. These human ectopic artificial livers (HEALs) stabilize the function of cryopreserved primary human hepatocytes through juxtacrine and paracrine signals in polymeric scaffolds. In contrast to current methods, HEALs can be efficiently established in immunocompetent mice with normal liver function. Mice transplanted with HEALs exhibit humanized liver functions persistent for weeks, including synthesis of human proteins, human drug metabolism, drug-drug interaction, and drug-induced liver injury. Here, mice with HEALs are used to predict the disproportionate metabolism and toxicity of "major" human metabolites using multiple routes of administration and monitoring. These advances may enable manufacturing of reproducible in vivo models for diverse drug development and research applications.

  5. Long non-coding RNA ATB promotes growth and epithelial-mesenchymal transition and predicts poor prognosis in human prostate carcinoma

    PubMed Central

    XU, SONG; YI, XIAO-MING; TANG, CHAO-PENG; GE, JING-PING; ZHANG, ZHENG-YU; ZHOU, WEN-QUAN

    2016-01-01

    Long non-coding RNAs (lncRNAs) have been identified to be critical mediators in various tumors associated with cancer progression. Long non-coding RNA activated by TGF-β (lncRNA-ATB) is a stimulator of epithelial-mesenchymal transition (EMT) and serves as a novel prognostic biomarker for hepatocellular carcinoma. However, the biological role and clinical significance of lncRNA-ATB in human prostate cancer have yet to be fully elucidated. The present study was designed to explore the expression of lncRNA-ATB in human prostate cancer patients and the role of lncRNA-ATB in prostate cancer cells. We showed that lncRNA-ATB expression was significantly upregulated in tumor tissues in patients with prostate cancer in comparison with adjacent non-tumor tissues. Further analysis indicted that high lncRNA-ATB expression may be an independent prognostic factor for biochemical recurrence (BCR)-free survival in prostate cancer patients. Overexpression of lncRNA-ATB promoted, and knockdown of lncRNA-ATB inhibited the growth of prostate cancer cells via regulations of cell cycle regulatory protein expression levels. In addition, lncRNA-ATB stimulated epithelial-mesenchymal transition (EMT) associated with ZEB1 and ZNF217 expression levels via ERK and PI3K/AKT signaling pathways. These results indicated that lncRNA-ATB may be considered as a new predictor in the clinical prognosis of patients with prostate cancer. Overexpression of lncRNA-ATB exerts mitogenic and EMT effects of prostate cancer via activation of ERK and PI3K/AKT signaling pathways. PMID:27176634

  6. Automated high-throughput assessment of prostate biopsy tissue using infrared spectroscopic chemical imaging

    NASA Astrophysics Data System (ADS)

    Bassan, Paul; Sachdeva, Ashwin; Shanks, Jonathan H.; Brown, Mick D.; Clarke, Noel W.; Gardner, Peter

    2014-03-01

    Fourier transform infrared (FT-IR) chemical imaging has been demonstrated as a promising technique to complement histopathological assessment of biomedical tissue samples. Current histopathology practice involves preparing thin tissue sections and staining them using hematoxylin and eosin (H&E) after which a histopathologist manually assess the tissue architecture under a visible microscope. Studies have shown that there is disagreement between operators viewing the same tissue suggesting that a complementary technique for verification could improve the robustness of the evaluation, and improve patient care. FT-IR chemical imaging allows the spatial distribution of chemistry to be rapidly imaged at a high (diffraction-limited) spatial resolution where each pixel represents an area of 5.5 × 5.5 μm2 and contains a full infrared spectrum providing a chemical fingerprint which studies have shown contains the diagnostic potential to discriminate between different cell-types, and even the benign or malignant state of prostatic epithelial cells. We report a label-free (i.e. no chemical de-waxing, or staining) method of imaging large pieces of prostate tissue (typically 1 cm × 2 cm) in tens of minutes (at a rate of 0.704 × 0.704 mm2 every 14.5 s) yielding images containing millions of spectra. Due to refractive index matching between sample and surrounding paraffin, minimal signal processing is required to recover spectra with their natural profile as opposed to harsh baseline correction methods, paving the way for future quantitative analysis of biochemical signatures. The quality of the spectral information is demonstrated by building and testing an automated cell-type classifier based upon spectral features.

  7. [Human lung connective tissue in postnatal ontogeny].

    PubMed

    Kasimtsev, A A; Nikolaev, V G

    1993-01-01

    Changes of the connective tissue structures, appearing during all postnatal ontogenesis stages were studied in 147 human lung specimens of different age groups (from newborns up to 82-year-olds). Qualitative and quantitative composition of connective tissue structures changes with the age which leads to the lateral aggregation of the fibers and growth of the general mass of the connective tissue. Heterochronia of the age variability manifestations in different regions of the lung framework was demonstrated. The original age transformations of connective tissue structures are characteristic for the basal lung regions. With the exception of perivasal connective tissue, similar changes in the region of the lung apexes appear 3-5 years later. This gives an opportunity to distinguish three anatomic zones in the lungs in an apico-basal direction, characterising the local nature of the age changes manifestations.

  8. Tissue-scale, personalized modeling and simulation of prostate cancer growth.

    PubMed

    Lorenzo, Guillermo; Scott, Michael A; Tew, Kevin; Hughes, Thomas J R; Zhang, Yongjie Jessica; Liu, Lei; Vilanova, Guillermo; Gomez, Hector

    2016-11-29

    Recently, mathematical modeling and simulation of diseases and their treatments have enabled the prediction of clinical outcomes and the design of optimal therapies on a personalized (i.e., patient-specific) basis. This new trend in medical research has been termed "predictive medicine." Prostate cancer (PCa) is a major health problem and an ideal candidate to explore tissue-scale, personalized modeling of cancer growth for two main reasons: First, it is a small organ, and, second, tumor growth can be estimated by measuring serum prostate-specific antigen (PSA, a PCa biomarker in blood), which may enable in vivo validation. In this paper, we present a simple continuous model that reproduces the growth patterns of PCa. We use the phase-field method to account for the transformation of healthy cells to cancer cells and use diffusion-reaction equations to compute nutrient consumption and PSA production. To accurately and efficiently compute tumor growth, our simulations leverage isogeometric analysis (IGA). Our model is shown to reproduce a known shape instability from a spheroidal pattern to fingered growth. Results of our computations indicate that such shift is a tumor response to escape starvation, hypoxia, and, eventually, necrosis. Thus, branching enables the tumor to minimize the distance from inner cells to external nutrients, contributing to cancer survival and further development. We have also used our model to perform tissue-scale, personalized simulation of a PCa patient, based on prostatic anatomy extracted from computed tomography images. This simulation shows tumor progression similar to that seen in clinical practice.

  9. Tissue-scale, personalized modeling and simulation of prostate cancer growth

    PubMed Central

    Lorenzo, Guillermo; Scott, Michael A.; Tew, Kevin; Hughes, Thomas J. R.; Zhang, Yongjie Jessica; Liu, Lei; Vilanova, Guillermo; Gomez, Hector

    2016-01-01

    Recently, mathematical modeling and simulation of diseases and their treatments have enabled the prediction of clinical outcomes and the design of optimal therapies on a personalized (i.e., patient-specific) basis. This new trend in medical research has been termed “predictive medicine.” Prostate cancer (PCa) is a major health problem and an ideal candidate to explore tissue-scale, personalized modeling of cancer growth for two main reasons: First, it is a small organ, and, second, tumor growth can be estimated by measuring serum prostate-specific antigen (PSA, a PCa biomarker in blood), which may enable in vivo validation. In this paper, we present a simple continuous model that reproduces the growth patterns of PCa. We use the phase-field method to account for the transformation of healthy cells to cancer cells and use diffusion−reaction equations to compute nutrient consumption and PSA production. To accurately and efficiently compute tumor growth, our simulations leverage isogeometric analysis (IGA). Our model is shown to reproduce a known shape instability from a spheroidal pattern to fingered growth. Results of our computations indicate that such shift is a tumor response to escape starvation, hypoxia, and, eventually, necrosis. Thus, branching enables the tumor to minimize the distance from inner cells to external nutrients, contributing to cancer survival and further development. We have also used our model to perform tissue-scale, personalized simulation of a PCa patient, based on prostatic anatomy extracted from computed tomography images. This simulation shows tumor progression similar to that seen in clinical practice. PMID:27856758

  10. Tissue-scale, personalized modeling and simulation of prostate cancer growth