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Sample records for psca prostate stem

  1. Prostate stem cell antigen (PSCA) expression increases with high gleason score, advanced stage and bone metastasis in prostate cancer.

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    Gu, Z; Thomas, G; Yamashiro, J; Shintaku, I P; Dorey, F; Raitano, A; Witte, O N; Said, J W; Loda, M; Reiter, R E

    2000-03-02

    Prostate stem cell antigen (PSCA) is a recently defined homologue of the Thy-1/Ly-6 family of glycosylphosphatidylinositol (GPI)-anchored cell surface antigens. PSCA mRNA is expressed in the basal cells of normal prostate and in more than 80% of prostate cancers. The purpose of the present study was to examine PSCA protein expression in clinical specimens of human prostate cancer. Five monoclonal antibodies were raised against a PSCA-GST fusion protein and screened for their ability to recognize PSCA on the cell surface of human prostate cancer cells. Immunohistochemical analysis of PSCA expression was performed on paraffin-embedded sections from 25 normal tissues, 112 primary prostate cancers and nine prostate cancers metastatic to bone. The level of PSCA expression in prostate tumors was quantified and compared with expression in adjacent normal glands. The antibodies detect PSCA expression on the cell surface of normal and malignant prostate cells and distinguish three extracellular epitopes on PSCA. Prostate and transitional epithelium reacted strongly with PSCA. PSCA staining was also seen in placental trophoblasts, renal collecting ducts and neuroendocrine cells in the stomach and colon. All other normal tissues tested were negative. PSCA protein expression was identified in 105/112 (94%) primary prostate tumors and 9/9 (100%) bone metastases. The level of PSCA expression increased with higher Gleason score (P=0.016), higher tumor stage (P=0.010) and progression to androgen-independence (P=0. 021). Intense, homogeneous staining was seen in all nine bone metastases. PSCA is a cell surface protein with limited expression in extraprostatic normal tissues. PSCA expression correlates with tumor stage, grade and androgen independence and may have prognostic utility. Because expression on the surface of prostate cancer cells increases with tumor progression, PSCA may be a useful molecular target in advanced prostate cancer.

  2. An affinity matured minibody for PET imaging of prostate stem cell antigen (PSCA)-expressing tumors

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    Lepin, Eric J.; Leyton, Jeffrey V.; Olafsen, Tove; Salazar, Felix B.; McCabe, Katelyn E.; Wu, Anna M. [University of California, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, Los Angeles, CA (United States); Zhou, Yu; Marks, James D. [University of California, Department of Anesthesia, San Francisco, CA (United States); Hahm, Scott; Reiter, Robert E. [University of California, Department of Urology, David Geffen School of Medicine, Los Angeles, CA (United States)

    2010-08-15

    Prostate stem cell antigen (PSCA), a cell surface glycoprotein expressed in normal human prostate and bladder, is over-expressed in the majority of localized prostate cancer and most bone metastases. We have previously shown that the hu1G8 minibody, a humanized anti-PSCA antibody fragment (single-chain Fv-C{sub H}3 dimer, 80 kDa), can localize specifically and image PSCA-expressing xenografts at 21 h post-injection. However, the humanization and antibody fragment reformatting decreased its apparent affinity. Here, we sought to evaluate PET imaging contrast with affinity matured minibodies. Yeast scFv display, involving four rounds of selection, was used to generate the three affinity matured antibody fragments (A2, A11, and C5) that were reformatted into minibodies. These three affinity matured anti-PSCA minibodies were characterized in vitro, and following radiolabeling with {sup 124}I were evaluated in vivo for microPET imaging of PSCA-expressing tumors. The A2, A11, and C5 minibody variants all demonstrated improved affinity compared to the parental (P) minibody and were ranked as follows: A2 > A11 > C5 > P. The {sup 124}I-labeled A11 minibody demonstrated higher immunoreactivity than the parental minibody and also achieved the best microPET imaging contrast in two xenograft models, LAPC-9 (prostate cancer) and Capan-1 (pancreatic cancer), when evaluated in vivo. Of the affinity variant minibodies tested, the A11 minibody that ranked second in affinity was selected as the best immunoPET tracer to image PSCA-expressing xenografts. This candidate is currently under development for evaluation in a pilot clinical imaging study. (orig.)

  3. Novel PSCA targeting scFv-fusion proteins for diagnosis and immunotherapy of prostate cancer.

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    Kessler, Claudia; Pardo, Alessa; Tur, Mehmet K; Gattenlöhner, Stefan; Fischer, Rainer; Kolberg, Katharina; Barth, Stefan

    2017-10-01

    Despite great progress in the diagnosis and treatment of localized prostate cancer (PCa), there remains a need for new diagnostic markers that can accurately distinguish indolent and aggressive variants. One promising approach is the antibody-based targeting of prostate stem cell antigen (PSCA), which is frequently overexpressed in PCa. Here, we show the construction of a molecular imaging probe comprising a humanized scFv fragment recognizing PSCA genetically fused to an engineered version of the human DNA repair enzyme O6-alkylguanine-DNA alkyltransferase (AGT), the SNAP-tag, enabling specific covalent coupling to various fluorophores for diagnosis of PCa. Furthermore, the recombinant immunotoxin (IT) PSCA(scFv)-ETA' comprising the PSCA(scFv) and a truncated version of Pseudomonas exotoxin A (PE, ETA') was generated. We analyzed the specific binding and internalization behavior of the molecular imaging probe PSCA(scFv)-SNAP in vitro by flow cytometry and live cell imaging, compared to the corresponding IT PSCA(scFv)-ETA'. The cytotoxic activity of PSCA(scFv)-ETA' was tested using cell viability assays. Specific binding was confirmed on formalin-fixed paraffin-embedded tissue specimen of early and advanced PCa. Alexa Fluor® 647 labeling of PSCA(scFv)-SNAP confirmed selective binding to PSCA, leading to rapid internalization into the target cells. The recombinant IT PSCA(scFv)-ETA' showed selective binding leading to internalization and efficient elimination of target cells. Our data demonstrate, for the first time, the specific binding, internalization, and cytotoxicity of a scFv-based fusion protein targeting PSCA. Immunohistochemical staining confirmed the specific ex vivo binding to primary PCa material.

  4. Multifunctional PSCA Antibody Fragments for PET and Optical Prostate Cancer Imaging

    Science.gov (United States)

    2016-10-01

    genetically engineered models of prostate cancer 4) Major Task 4: Image bone and lymph node in xenograft models 5) Major Task 5: Image transgenic...models of prostate cancer including bone and lymph node metastasis models as well as genetically engineered mouse models. We will also begin to apply...We are developing imaging probes based on engineered antibodies that recognize PSCA (prostate stem cell antigen), a cell surface protein highly

  5. Antiproliferative and Apoptotic Effects of a Specific Antiprostate Stem Cell Single Chain Antibody on Human Prostate Cancer Cells

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    Foroogh Nejatollahi

    2013-01-01

    Full Text Available Prostate stem cell antigen (PSCA is a highly glycosylated cell surface protein which is overexpressed in several malignancies including prostate, pancreas, and urinary bladder cancers. Tumor suppression has been reported by anti-PSCA antibody. Small and high affinity single chain antibodies (scFv have been introduced as effective agents for cancer immunotargeting approaches. In the present study, we used a phage antibody display library of scFv and selected two antibodies against two immunodominant epitopes of PSCA by panning process. The reactivity of the scFvs for the corresponding epitopes was determined by phage ELISA. The binding specificity of antibodies to PSCA-expressing prostate cancer cell line, DU-145, was analyzed by flow cytometry. The antiproliferative and apoptotic induction effects were evaluated by MTT and Annexin-V assays, respectively. Results represented functional scFv C5-II which could bind specifically to DU-145 cells and significantly inhibited the proliferation of these cells (61% with no effect on PSCA-negative cells. The antibody also induced apoptosis in the PSCA expressing cells. The percentage of the apoptotic cells after 24 hrs of exposure to 500 scFv/cell was 33.80%. These results demonstrate that the functional anti-PSCA scFv C5-II has the potential to be considered as a new agent for targeted therapy of prostate cancer.

  6. Retargeting of T lymphocytes to PSCA- or PSMA positive prostate cancer cells using the novel modular chimeric antigen receptor platform technology "UniCAR".

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    Feldmann, Anja; Arndt, Claudia; Bergmann, Ralf; Loff, Simon; Cartellieri, Marc; Bachmann, Dominik; Aliperta, Roberta; Hetzenecker, Mirjam; Ludwig, Florian; Albert, Susann; Ziller-Walter, Pauline; Kegler, Alexandra; Koristka, Stefanie; Gärtner, Sebastian; Schmitz, Marc; Ehninger, Armin; Ehninger, Gerhard; Pietzsch, Jens; Steinbach, Jörg; Bachmann, Michael

    2017-05-09

    New treatment options especially of solid tumors including for metastasized prostate cancer (PCa) are urgently needed. Recent treatments of leukemias with chimeric antigen receptors (CARs) underline their impressive therapeutic potential. However CARs currently applied in the clinics cannot be repeatedly turned on and off potentially leading to severe life threatening side effects. To overcome these problems, we recently described a modular CAR technology termed UniCAR: UniCAR T cells are inert but can be turned on by application of one or multiple target modules (TMs). Here we present preclinical data summarizing the retargeting of UniCAR T cells to PCa cells using TMs directed to prostate stem cell- (PSCA) or/and prostate specific membrane antigen (PSMA). In the presence of the respective TM(s), we see a highly efficient target-specific and target-dependent activation of UniCAR T cells, secretion of pro-inflammatory cytokines, and PCa cell lysis both in vitro and experimental mice.

  7. Decrease in PSCA expression caused by Helicobacter pylori infection may promote progression to severe gastritis

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    Toyoshima, Osamu; Tanikawa, Chizu; Yamamoto, Ryuta; Watanabe, Hidenobu; Yamashita, Hiroharu; Sakitani, Kosuke; Yoshida, Shuntaro; Kubo, Michiaki; Matsuo, Keitaro; Ito, Hidemi; Koike, Kazuhiko; Seto, Yasuyuki; Matsuda, Koichi

    2018-01-01

    SNP rs2294008 in Prostate Stem Cell Antigen (PSCA) and decreased PSCA expression are associated with gastric cancer. The objective of this study is to investigate the role of rs2294008 and PSCA expression in the gastritis-gastric cancer carcinogenic pathway. We conducted a case-control association study of H. pylori-infected gastritis and gastric cancer. rs2294008 was associated with the progression to chronic active gastritis (P = 9.4 × 10–5; odds ratio = 3.88, TT + TC vs CC genotype), but not with H. pylori infection per se nor with the progression from active gastritis to gastric cancer. We also assessed the association of rs2294008 with PSCA mRNA expression in the gastric mucosa at various disease stages and found that rs2294008 was associated with PSCA expression (P = 1.3 × 10–12). H. pylori infection (P = 5.1 × 10–8) and eradication therapy (P gastritis compared with mild gastritis only among T allele carriers. Our findings revealed the regulation of PSCA expression by host genetic variation and bacterial infection might contribute to gastritis progression after H. pylori infection. PMID:29423095

  8. Prostate cancer stem cells.

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    Tu, Shi-Ming; Lin, Sue-Hwa

    2012-06-01

    Stem cells have long been implicated in prostate gland formation. The prostate undergoes regression after androgen deprivation and regeneration after testosterone replacement. Regenerative studies suggest that these cells are found in the proximal ducts and basal layer of the prostate. Many characteristics of prostate cancer indicate that it originates from stem cells. For example, the putative androgen receptor-negative (AR(-)) status of prostate stem cells renders them inherently insensitive to androgen blockade therapy. The androgen-regulated gene fusion TMPRSS2-ERG could be used to clarify both the cells of origin and the evolution of prostate cancer cells. In this review, we show that the hypothesis that distinct subtypes of cancer result from abnormalities within specific cell types-the stem cell theory of cancer-may instigate a major paradigm shift in cancer research and therapy. Ultimately, the stem cell theory of cancers will affect how we practice clinical oncology: our diagnosis, monitoring, and therapy of prostate and other cancers. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Prostate stem cell antigen gene TT genotype and development of intestinal metaplasia in Helicobacter pylori infection.

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    Uotani, Takahiro; Sugimoto, Mitsushige; Ichikawa, Hitomi; Tanaka, Shingo; Nagashima, Hiroyuki; Uchida, Tomohisa; Graham, David Y; Yamaoka, Yoshio

    2016-01-01

    Gastric cancer is etiologically related to interactions between Helicobacter pylori (H. pylori) infection, environmental and host factors. Gastric carcinoma is associated with a cascade of increasing atrophic gastric mucosal damage. Prostate stem cell antigen (PSCA) polymorphisms have been associated with an increased risk of gastric cancer. We aimed to examine the interaction between PSCA polymorphisms and H. pylori in the progression of H. pylori-related gastritis. The genotypes (TT, TC and CC) of PSCA single nucleotide polymorphism rs2294008 among H. pylori infected and uninfected Bhutanese were compared with the severity of H. pylori-related gastritis [neutrophils, monocytes, atrophy scores, H. pylori density, and the presence and extent of intestinal metaplasia (IM)] using the updated Sydney system. Biopsies from 339 participants were included. The proportion of biopsies with IM was significantly (P < 0.05) greater in those with the TT genotype than in either those with the CT or CC genotype. Although no significant differences were found in inflammation or H. pylori density scores, the scores for IM at both gastric corpus and antrum among participants infected by H. pylori with the TT genotype was significantly (P < 0.05) greater than in the C allele carriers. PSCA TT genotype is associated with a more than a threefold increase in the prevalence and the extent of gastric mucosal IM compared to C allele carriers among H. pylori-infected Bhutanese. © 2016 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

  10. Association of rs2294008 and rs9297976 Polymorphisms in PSCA Gene with Gastric Cancer Susceptibility in Uzbekistan.

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    Turdikulova, Shahlo; Dalimova, Dilbar; Abdurakhimov, Abror; Adilov, Bekzod; Navruzov, Sarimbek; Yusupbekov, Abror; Djuraev, Mirjalol; Abdujapparov, Suleyman; Egamberdiev, Dilshod; Mukhamedov, Rustam

    2016-01-01

    Genetic factors play an important role in the development of gastric cancer (GC), a prevalent malignancy in Central Asia. Recent studies have shown that single-nucleotide polymorphisms (SNPs) in several genes are associated with increased GC risk, indicating that genetic variation contributes to gastric carcinogenesis. Located on chromosome 8q24.2, the prostate stem cell antigen (PSCA) gene encodes a 123-amino acid glycoprotein related to the cell-proliferation inhibition and cell-death induction activity. SNPs in PSCA gene have been found to be associated with gastric cancer risk in a genome-wide association study, but results were not conclusive. This study aimed to investigate the association between two polymorphic variants of PSCA gene (rs2294008 and rs9297976) and the susceptibility to gastric cancer in Uzbekistan. Two hundred sixty eight patients with gastric cancer and a control group of 248 healthy individuals were included in this study. DNA samples isolated from these groups were genotyped using PCR-RFLP method. Comparative analysis of resulting genotypes showed a statistically significant association between CT genotype and gastric cancer (p=0.03, additive model of inheritance, Cochran-Armitage trend test). Comparative analysis of the distribution of genotypes of rs2976392 polymorphism did not show a statistically significant difference; however, analysis of the distribution of the rs2976392 genotypes in a subgroup of young women revealed a statistically significant (p = 0.04, additive model of inheritance, Cochran-Armitage trend test) increase in the incidence of AA (38%) and AG (56%) genotypes in patients with GC, compared to the controls (20% and 40%). Our findings support that PSCA rs2294008 and rs9297976 polymorphism may contribute to the susceptibility to gastric cancer. Genotyping of these polymorphisms can potentially be recommended as one of the criteria for identification of high risk groups for gastric cancer development in Uzbekistan.

  11. Positron Emission Tomographic Imaging of Iodine 124 Anti–Prostate Stem Cell Antigen–Engineered Antibody Fragments in LAPC-9 Tumor–Bearing Severe Combined Immunodeficiency Mice

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    Jeffrey V. Leyton

    2013-05-01

    Full Text Available The humanized antibody (hu1G8 has been shown to localize to prostate stem cell antigen (PSCA and image PSCA-positive xenografts. We previously constructed hu1G8 anti-PSCA antibody fragments and tested them for tumor targeting and the ability to image prostate cancer at early and late time points postinjection by positron emission tomography (PET. We now then compare the PET imaging and the radioactivity accumulation properties in prostate cancer tumors and nontarget tissues to determine the superior 124I-labeled hu1G8 antibody format. 124I-labeled diabody, minibody, scFv-Fc, scFv-Fc double mutant (DM, and parental IgG were administered into severe combined immunodeficiency (SCID mice bearing LAPC-9 xenografts and followed by whole-body PET imaging of mice at preselected time points. Regions of interest were manually drawn around tumor and nontarget tissues and evaluated for radioactivity accumulation. The 124I-hu1G8 IgG has its best time point for tumor high-contrast imaging at 168 hours postinjection. The 124I-hu1G8 minibody at 44 hours postinjection results in superior tumor high-contrast imaging compared to the other antibody formats. The 124I-hu1G8 minibody at 44 hours postinjection also has comparable percent tumor radioactivity compared to 124I-hu1G8 IgG at 168 hours postinjection. The 124I-hu1G8 minibody is the best engineered hu1G8 antibody format for imaging prostate cancer.

  12. Missense allele of a single nucleotide polymorphism rs2294008 attenuated antitumor effects of prostate stem cell antigen in gallbladder cancer cells

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    Hiroe Ono

    2013-01-01

    Full Text Available Background: Prostate stem cell antigen (PSCA, an organ-dependent tumor suppressor, is down regulated in gallbladder cancer (GBC. It is anticipated that the missense allele C of the single nucleotide polymorphism (SNP rs2294008 (T/C in the translation initiation codon of the gene affects the gene′s biological function and has some influence on GBC susceptibility. We examined the biological effect of the C allele on the function of the gene and the relation between the C allele and GBC susceptibility. Materials and Methods: Functional analysis of the SNP was conducted by introducing PSCA cDNA harboring the allele to a GBC cell line TGBC- 1TKB and performing colony formation assays in vitro and tumor formation assays in mice. The effect on transcriptional regulation was assessed by reporter assays. The association study was conducted on 44 Japanese GBC cases and 173 controls. Results: The PSCA cDNA harboring the C allele showed lower cell growth inhibition activity (20% reduction than that with the T allele. Concordantly, when injected into subcutaneous tissues of mice, the GBC cell line stably expressing the cDNA with the C allele formed tumors of almost the same size as that of the control cells, but the cell line expressing the cDNA with the T allele showed slower growth. The upstream DNA fragment harboring the C allele had more transcriptional activity than that with the T allele. The C allele showed positive correlation to GBC but no statistical significant odds ratio (OR = 1.77, 95% confidence interval 0.85-3.70, P value = 0.127 in dominant model. Conclusions: The missense allele was shown to have a biological effect, attenuating antitumor activities of PSCA, and consequently it may be a potential risk for GBC development. An association study in a larger sample size may reveal a significant association between the allele and GBC.

  13. Missense allele of a single nucleotide polymorphism rs2294008 attenuated antitumor effects of prostate stem cell antigen in gallbladder cancer cells.

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    Ono, Hiroe; Chihara, Dai; Chiwaki, Fumiko; Yanagihara, Kazuyoshi; Sasaki, Hiroki; Sakamoto, Hiromi; Tanaka, Hideo; Yoshida, Teruhiko; Saeki, Norihisa; Matsuo, Keitaro

    2013-01-01

    Prostate stem cell antigen (PSCA), an organ-dependent tumor suppressor, is down regulated in gallbladder cancer (GBC). It is anticipated that the missense allele C of the single nucleotide polymorphism (SNP) rs2294008 (T/C) in the translation initiation codon of the gene affects the gene's biological function and has some influence on GBC susceptibility. We examined the biological effect of the C allele on the function of the gene and the relation between the C allele and GBC susceptibility. Functional analysis of the SNP was conducted by introducing PSCA cDNA harboring the allele to a GBC cell line TGBC- 1TKB and performing colony formation assays in vitro and tumor formation assays in mice. The effect on transcriptional regulation was assessed by reporter assays. The association study was conducted on 44 Japanese GBC cases and 173 controls. The PSCA cDNA harboring the C allele showed lower cell growth inhibition activity (20% reduction) than that with the T allele. Concordantly, when injected into subcutaneous tissues of mice, the GBC cell line stably expressing the cDNA with the C allele formed tumors of almost the same size as that of the control cells, but the cell line expressing the cDNA with the T allele showed slower growth. The upstream DNA fragment harboring the C allele had more transcriptional activity than that with the T allele. The C allele showed positive correlation to GBC but no statistical significant odds ratio (OR = 1.77, 95% confidence interval 0.85-3.70, P value = 0.127 in dominant model). The missense allele was shown to have a biological effect, attenuating antitumor activities of PSCA, and consequently it may be a potential risk for GBC development. An association study in a larger sample size may reveal a significant association between the allele and GBC.

  14. Stem cells in prostate cancer.

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    Mateo, Francesca; Fernandez, Pedro L; Thomson, Timothy M

    2013-06-01

    Tumors constitute complex ecosystems with multiple interactions among neoplastic cells displaying various phenotypes and functions and where the tumoral niche is built with an active participation of the host environment that also impacts the malignant progression of the tumor cells. Irrespective of the cell of origin of prostate adenocarcinoma, mounting evidences support the existence of a hierarchy within neoplastic prostate cells that contributes to the heterogeneity of these tumors. At the origin of this hierarchy are small populations of tumor cells with high self-renewal potential and also capable of generating progeny tumor cells that lose self-renewal properties as they acquire more differentiated phenotypes. These cancer stem cells (CSC) depend on active gene networks that confer them with their self-renewal capacity through symmetrical divisions whereas they can also undergo asymmetrical division and differentiation either as stochastic events or in response to environmental cues. Although new experimental evidences indicate that this is can be a reversible process, thus blurring the distinction between CSCs and non-CSCs, the former are considered as the drivers of tumor growth and evolution, and thus a prime target for therapeutic intervention. Of particular importance in prostate cancer, CSCs may constitute the repository population of androgen-insensitive and chemotherapy-resistant tumor cells responsible for castration-resistant and chemotherapy-insensitive tumors, thus their identification and quantification in primary and metastatic neoplasms could play important roles in the management of this disease.

  15. Prostate Cancer Stem Cells: Research Advances

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    Dagmara Jaworska

    2015-11-01

    Full Text Available Cancer stem cells have been defined as cells within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. Experimental evidence showed that these highly tumorigenic cells might be responsible for initiation and progression of cancer into invasive and metastatic disease. Eradicating prostate cancer stem cells, the root of the problem, has been considered as a promising target in prostate cancer treatment to improve the prognosis for patients with advanced stages of the disease.

  16. Proximal location of mouse prostate epithelial stem cells

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    Tsujimura, Akira; Koikawa, Yasuhiro; Salm, Sarah; Takao, Tetsuya; Coetzee, Sandra; Moscatelli, David; Shapiro, Ellen; Lepor, Herbert; Sun, Tung-Tien; Wilson, E. Lynette

    2002-01-01

    Stem cells are believed to regulate normal prostatic homeostasis and to play a role in the etiology of prostate cancer and benign prostatic hyperplasia. We show here that the proximal region of mouse prostatic ducts is enriched in a subpopulation of epithelial cells that exhibit three important attributes of epithelial stem cells: they are slow cycling, possess a high in vitro proliferative potential, and can reconstitute highly branched glandular ductal structures in collagen gels. We propos...

  17. Forced LIGHT expression in prostate tumors overcomes Treg mediated immunosuppression and synergizes with a prostate tumor therapeutic vaccine by recruiting effector T lymphocytes.

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    Yan, Lisa; Da Silva, Diane M; Verma, Bhavna; Gray, Andrew; Brand, Heike E; Skeate, Joseph G; Porras, Tania B; Kanodia, Shreya; Kast, W Martin

    2015-02-15

    LIGHT, a ligand for lymphotoxin-β receptor (LTβR) and herpes virus entry mediator, is predominantly expressed on activated immune cells and LTβR signaling leads to the recruitment of lymphocytes. The interaction between LIGHT and LTβR has been previously shown to activate immune cells and result in tumor regression in a virally-induced tumor model, but the role of LIGHT in tumor immunosuppression or in a prostate cancer setting, where self antigens exist, has not been explored. We hypothesized that forced expression of LIGHT in prostate tumors would shift the pattern of immune cell infiltration toward an anti-tumoral milieu, would inhibit T regulatory cells (Tregs) and would induce prostate cancer tumor associated antigen (TAA) specific T cells that would eradicate tumors. Real Time PCR was used to evaluate expression of forced LIGHT and other immunoregulatory genes in prostate tumors samples. For in vivo studies, adenovirus encoding murine LIGHT was injected intratumorally into TRAMP-C2 prostate cancer cell tumor bearing mice. Chemokine and cytokine concentrations were determined by multiplex ELISA. Flow cytometry was used to phenotype tumor infiltrating lymphocytes and expression of LIGHT on the tumor cell surface. Tumor-specific lymphocytes were quantified via ELISpot assay. Treg induction and Treg suppression assays determined Treg functionality after LIGHT treatment. LIGHT in combination with a therapeutic vaccine, PSCA TriVax, reduced tumor burden. LIGHT expression peaked within 48 hr of infection, recruited effector T cells that recognized mouse prostate stem cell antigen (PSCA) into the tumor microenvironment, and inhibited infiltration of Tregs. Tregs isolated from tumor draining lymph nodes had impaired suppressive capability after LIGHT treatment. Forced LIGHT treatment combined with PSCA TriVax therapeutic vaccination delays prostate cancer progression in mice by recruiting effector T lymphocytes to the tumor and inhibiting Treg mediated

  18. A basal stem cell signature identifies aggressive prostate cancer phenotypes

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    Smith, Bryan A.; Sokolov, Artem; Uzunangelov, Vladislav; Baertsch, Robert; Newton, Yulia; Graim, Kiley; Mathis, Colleen; Cheng, Donghui; Stuart, Joshua M.; Witte, Owen N.

    2015-01-01

    Evidence from numerous cancers suggests that increased aggressiveness is accompanied by up-regulation of signaling pathways and acquisition of properties common to stem cells. It is unclear if different subtypes of late-stage cancer vary in stemness properties and whether or not these subtypes are transcriptionally similar to normal tissue stem cells. We report a gene signature specific for human prostate basal cells that is differentially enriched in various phenotypes of late-stage metastatic prostate cancer. We FACS-purified and transcriptionally profiled basal and luminal epithelial populations from the benign and cancerous regions of primary human prostates. High-throughput RNA sequencing showed the basal population to be defined by genes associated with stem cell signaling programs and invasiveness. Application of a 91-gene basal signature to gene expression datasets from patients with organ-confined or hormone-refractory metastatic prostate cancer revealed that metastatic small cell neuroendocrine carcinoma was molecularly more stem-like than either metastatic adenocarcinoma or organ-confined adenocarcinoma. Bioinformatic analysis of the basal cell and two human small cell gene signatures identified a set of E2F target genes common between prostate small cell neuroendocrine carcinoma and primary prostate basal cells. Taken together, our data suggest that aggressive prostate cancer shares a conserved transcriptional program with normal adult prostate basal stem cells. PMID:26460041

  19. Prostate Stem Cells in the Development of Benign Prostate Hyperplasia and Prostate Cancer: Emerging Role and Concepts

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    Akhilesh Prajapati

    2013-01-01

    Full Text Available Benign Prostate hyperplasia (BPH and prostate cancer (PCa are the most common prostatic disorders affecting elderly men. Multiple factors including hormonal imbalance, disruption of cell proliferation, apoptosis, chronic inflammation, and aging are thought to be responsible for the pathophysiology of these diseases. Both BPH and PCa are considered to be arisen from aberrant proliferation of prostate stem cells. Recent studies on BPH and PCa have provided significant evidence for the origin of these diseases from stem cells that share characteristics with normal prostate stem cells. Aberrant changes in prostate stem cell regulatory factors may contribute to the development of BPH or PCa. Understanding these regulatory factors may provide insight into the mechanisms that convert quiescent adult prostate cells into proliferating compartments and lead to BPH or carcinoma. Ultimately, the knowledge of the unique prostate stem or stem-like cells in the pathogenesis and development of hyperplasia will facilitate the development of new therapeutic targets for BPH and PCa. In this review, we address recent progress towards understanding the putative role and complexities of stem cells in the development of BPH and PCa.

  20. Prostate stem cells in the development of benign prostate hyperplasia and prostate cancer: emerging role and concepts.

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    Prajapati, Akhilesh; Gupta, Sharad; Mistry, Bhavesh; Gupta, Sarita

    2013-01-01

    Benign Prostate hyperplasia (BPH) and prostate cancer (PCa) are the most common prostatic disorders affecting elderly men. Multiple factors including hormonal imbalance, disruption of cell proliferation, apoptosis, chronic inflammation, and aging are thought to be responsible for the pathophysiology of these diseases. Both BPH and PCa are considered to be arisen from aberrant proliferation of prostate stem cells. Recent studies on BPH and PCa have provided significant evidence for the origin of these diseases from stem cells that share characteristics with normal prostate stem cells. Aberrant changes in prostate stem cell regulatory factors may contribute to the development of BPH or PCa. Understanding these regulatory factors may provide insight into the mechanisms that convert quiescent adult prostate cells into proliferating compartments and lead to BPH or carcinoma. Ultimately, the knowledge of the unique prostate stem or stem-like cells in the pathogenesis and development of hyperplasia will facilitate the development of new therapeutic targets for BPH and PCa. In this review, we address recent progress towards understanding the putative role and complexities of stem cells in the development of BPH and PCa.

  1. Oct-4 expression maintained stem cell properties in prostate cancer ...

    African Journals Online (AJOL)

    The purpose of the present study is to isolate cancerous stem-like cells from normal healthy volunteers and prostate cancer patients (CD133+) which also express MDR1 and to ascertain the influence of Oct-4 on 'stem-ness' and differentiation of these CD133+ cells towards epithelium. Methods: CD133+ cells were isolated ...

  2. Forced LIGHT expression in prostate tumors overcomes Treg mediated immunosuppression and synergizes with a prostate tumor therapeutic vaccine by recruiting effector T lymphocytes

    Science.gov (United States)

    Yan, Lisa; Da Silva, Diane M.; Verma, Bhavna; Gray, Andrew; Brand, Heike E.; Skeate, Joseph G.; Porras, Tania B.; Kanodia, Shreya; Kast, W. Martin

    2014-01-01

    Background LIGHT, a ligand for lymphotoxin-β receptor (LTβR) and herpes virus entry mediator, is predominantly expressed on activated immune cells and LTβR signaling leads to the recruitment of lymphocytes. The interaction between LIGHT and LTβR has been previously shown in a virus induced tumor model to activate immune cells and result in tumor regression, but the role of LIGHT in tumor immunosuppression or in a prostate cancer setting, where self antigens exist, has not been explored. We hypothesized that forced expression of LIGHT in prostate tumors would shift the pattern of immune cell infiltration, would inhibit T regulatory cells (Tregs) and would induce prostate cancer tumor associated antigen (TAA) specific T cells that would eradicate tumors. Methods Real Time PCR was used to evaluate expression of forced LIGHT and various other genes in prostate tumors samples. Adenovirus encoding murine LIGHT was injected intratumorally into TRAMP C2 prostate cancer cell tumor bearing mice for in vivo studies. Chemokine and cytokine concentrations were determined by multiplex ELISA. Flow cytometry was used to phenotype tumor infiltrating lymphocytes and expression of LIGHT on the tumor cell surface. Tumor specific lymphocytes were quantified via an ELISpot assay. Treg induction and Treg suppression assays determined Treg functionality after LIGHT treatment. Results LIGHT expression peaked within 48 hours of infection, recruited effector T cells into the tumor microenvironment that recognized mouse prostate stem cell antigen (PSCA) and inhibited the infiltration of Tregs. Tregs isolated from tumor draining lymph nodes had impaired suppressive capability after LIGHT treatment. LIGHT in combination with a therapeutic vaccine, PSCA TriVax, reduced tumor burden. Conclusion Forced LIGHT treatment combined with PSCA TriVax therapeutic vaccination delays prostate cancer progression in mice by recruiting effector T lymphocytes to the tumor and inhibiting Treg mediated

  3. Low Testosterone Alters the Activity of Mouse Prostate Stem Cells.

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    Zhou, Ye; Copeland, Ben; Otto-Duessel, Maya; He, Miaoling; Markel, Susan; Synold, Tim W; Jones, Jeremy O

    2017-04-01

    Low serum testosterone (low T) has been repeatedly linked to worse outcomes in men with newly diagnosed prostate cancer (PC). How low T contributes to these outcomes is unknown. Here we demonstrate that exposure to low T causes significant changes in the mouse prostate and prostate stem cells. Mice were castrated and implanted with capsules to achieve castrate, normal, or sub-physiological levels of T. After 6 weeks of treatment, LC-MS/MS was used to quantify the levels of T and dihydrotestosterone (DHT) in serum and prostate tissue. FACS was used to quantify the percentages of purported prostate stem and transit amplifying (TA) cells in mouse prostates. Prostate tissues were also stained for the presence of CD68+ cells and RNA was extracted from prostate tissue or specific cell populations to measure changes in transcript levels with low T treatment. Despite having significantly different levels of T and DHT in the serum, T and DHT concentrations in prostate tissue from different T treatment groups were similar. Low T treatment resulted in significant alterations in the expression of androgen biosynthesis genes, which may be related to maintaining prostate androgen levels. Furthermore, the expression of androgen-regulated genes in the prostate was similar among all T treatment groups, demonstrating that the mouse prostate can maintain functional levels of androgens despite low serum T levels. Low T increased the frequency of prostate stem and TA cells in adult prostate tissue and caused major transcriptional changes in those cells. Gene ontology analysis suggested that low T caused inflammatory responses and immunofluorescent staining indicated that low T treatment led to the increased presence of CD68+ macrophages in prostate tissue. Low T alters the AR signaling axis which likely leads to maintenance of functional levels of prostate androgens. Low T also induces quantitative and qualitative changes in prostate stem cells which appear to lead to inflammatory

  4. The Role of AR- and VDR-Modulated miRNAs in Sensitization of Prostate Cancer Cells to Therapy

    Science.gov (United States)

    2012-10-01

    GMNN) or synergistically ( CCNA2 , CDC20, CCNB2, Survivin/BIRC5, GADD45G, E2F1, ITPR1, BRCA1). Genes that are known to modulate the cell cycle ( CCNA2 ...changes in the mRNA levels of cell cycle regulators. CCNA2 , GMNN, CDC20 and CCNB2 transcript levels were measured over a 72 h time course in LNCaP cells ...been rigorously evaluated (48). The cells express wild type AR and are positive for PSA, PCA3, PSCA (prostate stem cell antigen), PSMA (prostate

  5. Sca-1 expression identifies stem cells in the proximal region of prostatic ducts with high capacity to reconstitute prostatic tissue

    OpenAIRE

    Patricia E Burger; Xiong, Xiaozhong; Coetzee, Sandra; Salm, Sarah N.; Moscatelli, David; Goto, Ken; Wilson, E. Lynette

    2005-01-01

    We previously showed that prostatic stem cells are concentrated in the proximal regions of prostatic ducts. We now report that these stem cells can be purified from isolated proximal duct regions by virtue of their high expression of the cell surface protein stem cell antigen 1 (Sca-1). In an in vivo prostate reconstitution assay, the purified Sca-1-expressing cell population isolated from the proximal region of ducts was more effective in generating prostatic tissue than a comparable populat...

  6. Microenvironment -Programmed Metastatic Prostate Cancer Stem Cells (mPCSCs)

    Science.gov (United States)

    2016-10-01

    mPCSCs)” PI : Dean Tang 1. INTRODUCTION: The main goal of this IDEA project is to help elucidate the cellular and molecular mechanisms underlying...metastatic prostate cancer stem cells 3. ACCOMPLISHMENTS: Dr. Tang, the PI of this grant, together with most lab members, moved from the M.D...repressing CD44. Nat Med 17, 211-215 (2011). 5. Qin, J. et al. The PSA -/lo prostate cancer cell population harbors self-renewing long-term tumor

  7. Prostate Cancer Stem-Like Cells | Center for Cancer Research

    Science.gov (United States)

    Prostate cancer is the third leading cause of cancer-related death among men, killing an estimated 27,000 men each year in the United States. Men with advanced prostate cancer often become resistant to conventional therapies. Many researchers speculate that the emergence of resistance is due to the presence of cancer stem cells, which are believed to be a small subpopulation of tumor cells that can self-renew and give rise to more differentiated tumor cells. It is thought that these stem cells survive initial therapies (such as chemotherapy and hormone therapy) and then generate new tumor cells that are resistant to these standard treatments. If prostate cancer stem cells could be identified and characterized, it might be possible to design treatments that prevent resistance.

  8. Targeting Apoptotic Activity Against Prostate Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Dagmara Jaworska

    2017-07-01

    Full Text Available Numerous data suggest that an increase of cancer stem cells (CSCs in tumor mass can be the reason for failure of conventional therapies because of their resistance. CD44+/CD24− cells are a putative cancer stem cells subpopulation in prostate cancer. TRAIL (tumor necrosis factor-related apoptosis-inducing ligand is an activator of apoptosis in tumor cells. However, some tumors are TRAIL-resistant. Cancer cells can be re-sensitized to TRAIL induced apoptosis by a combination of TRAIL and taxanes. The aim of this work was to analyze the enhancement of the anticancer effect of TRAIL by paclitaxel, cabazitaxel and docetaxel in the whole population of PC3 and DU145 prostate cancer cells, but also in CD44+/CD24− prostate cancer stem cells. We examined the apoptotic effect of TRAIL and taxanes using flow cytometry and Annexin-V-PE staining. The co-treatment with taxanes and TRAIL enhanced significantly the apoptosis in CD44+/CD24− cells only in PC3 cell line but not in DU145 cells. We discovered also that taxanes can increase the expression of death receptor TRAIL-R2 in PC3 prostate cancer cells. The results of our study show that treatment with paclitaxel, cabazitaxel and docetaxel is able to enhance the apoptosis induced by TRAIL even in prostate cancer stem cells.

  9. Stem Cell Based Gene Therapy in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Jae Heon Kim

    2014-01-01

    Full Text Available Current prostate cancer treatment, especially hormone refractory cancer, may create profound iatrogenic outcomes because of the adverse effects of cytotoxic agents. Suicide gene therapy has been investigated for the substitute modality for current chemotherapy because it enables the treatment targeting the cancer cells. However the classic suicide gene therapy has several profound side effects, including immune-compromised due to viral vector. Recently, stem cells have been regarded as a new upgraded cellular vehicle or vector because of its homing effects. Suicide gene therapy using genetically engineered mesenchymal stem cells or neural stem cells has the advantage of being safe, because prodrug administration not only eliminates tumor cells but consequently kills the more resistant therapeutic stem cells as well. The attractiveness of prodrug cancer gene therapy by stem cells targeted to tumors lies in activating the prodrug directly within the tumor mass, thus avoiding systemic toxicity. Therapeutic achievements using stem cells in prostate cancer include the cytosine deaminase/5-fluorocytosine prodrug system, herpes simplex virus thymidine kinase/ganciclovir, carboxyl esterase/CPT11, and interferon-beta. The aim of this study is to review the stem cell therapy in prostate cancer including its proven mechanisms and also limitations.

  10. Mesenchymal Stem Cell-Based Therapy for Prostate Cancer

    Science.gov (United States)

    2014-09-01

    graft versus host disease, inflammatory bowel disease and myocardial infarction in clinical trials. These clinical studies have documented that... myocardial infarction in clinical trials. Conclusions These results document two things. First, the therapeutic agent loaded into hbMSCs must...Mesenchymal Stem Cell-Based Therapy for Prostate Cancer PRINCIPAL INVESTIGATOR: John Isaacs; Jeffrey Karp

  11. Novel regulators of prostate cancer stem cells and tumor aggressiveness

    NARCIS (Netherlands)

    Zoni, E.

    2016-01-01

    In the past decade it became increasingly clear that tumor heterogeneity represents one of the major problems for cancer treatment, also in prostate cancer. The identification of the molecular properties of highly aggressive cells (Cancer Stem Cells, CSCs) dispersed within the tumor represents a

  12. Vaccination with recombinant adenoviruses and dendritic cells expressing prostate-specific antigens is effective in eliciting CTL and suppresses tumor growth in the experimental prostate cancer.

    Science.gov (United States)

    Kim, Sol; Lee, Jee-Boong; Lee, Geon Kook; Chang, Jun

    2009-06-15

    Prostate cancer is currently the most commonly diagnosed cancer in men and the second leading cause of cancer-related death in men in the US. Immunological approaches may provide an alternative option for prevention and treatment of prostate cancer. To develop vaccine against prostate cancer using mouse model, we constructed three recombinant adenoviruses expressing prostate-specific membrane antigen (rAd/PSMA), prostate stem cell antigen (rAd/PSCA) and six-transmembrane epithelial antigen of the prostate (rAd/STEAP), that were specifically up-regulated in the transgenic murine prostate cancer. Male C57BL/6 mice were immunized by intravenous injection of these recombinant adenoviruses and subsequently by subcutaneous injection of dendritic cells pulsed with TRAMP-C1 tumor lysate. After subcutaneous challenge with TRAMP-C1 cells, tumor growth was significantly delayed in the immunized mice compared to the control group. Surprisingly, significant numbers of STEAP-specific CD8 T cells were detected in the peripheral blood and the spleen of immune mice using MHC I tetramers, and injection of rAd/STEAP alone followed by pulsed DC was sufficient to inhibit tumor growth. Therapeutic vaccination also significantly delayed the growth of pre-established tumors. Our results suggest that STEAP is a good immunologic target antigen against prostate cancer and our vaccination regimen successfully elicits anti-tumor CTL responses and suppresses tumor growth. More studies will expedite the development of this vaccine toward clinical application.

  13. CD133 does not enrich for the stem cell activity in vivo in adult mouse prostates

    Directory of Open Access Journals (Sweden)

    Xing Wei

    2016-05-01

    Full Text Available CD133 is widely used as a marker for stem/progenitor cells in many organ systems. Previous studies using in vitro stem cell assays have suggested that the CD133-expressing prostate basal cells may serve as the putative prostate stem cells. However, the precise localization of the CD133-expressing cells and their contributions to adult murine prostate homeostasis in vivo remain undetermined. We show that loss of function of CD133 does not impair murine prostate morphogenesis, homeostasis and regeneration, implying a dispensable role for CD133 in prostate stem cell function. Using a CD133-CreERT2 model in conjunction with a fluorescent report line, we show that CD133 is not only expressed in a fraction of prostate basal cells, but also in some luminal cells and stromal cells. CD133+ basal cells possess higher in vitro sphere-forming activities than CD133− basal cells. However, the in vivo lineage tracing study reveals that the two cell populations possess the same regenerative capacity and contribute equally to the maintenance of the basal cell lineage. Similarly, CD133+ and CD133− luminal cells are functionally equivalent in maintaining the luminal cell lineage. Collectively, our study demonstrates that CD133 does not enrich for the stem cell activity in vivo in adult murine prostate. This study does not contradict previous reports showing CD133+ cells as prostate stem cells in vitro. Instead, it highlights a substantial impact of biological contexts on cellular behaviors.

  14. Isolation and functional interrogation of adult human prostate epithelial stem cells at single cell resolution

    Directory of Open Access Journals (Sweden)

    Wen-Yang Hu

    2017-08-01

    Full Text Available Using primary cultures of normal human prostate epithelial cells, we developed a novel prostasphere-based, label-retention assay that permits identification and isolation of stem cells at a single cell level. Their bona fide stem cell nature was corroborated using in vitro and in vivo regenerative assays and documentation of symmetric/asymmetric division. Robust WNT10B and KRT13 levels without E-cadherin or KRT14 staining distinguished individual stem cells from daughter progenitors in spheroids. Following FACS to isolate label-retaining stem cells from label-free progenitors, RNA-seq identified unique gene signatures for the separate populations which may serve as useful biomarkers. Knockdown of KRT13 or PRAC1 reduced sphere formation and symmetric self-renewal highlighting their role in stem cell maintenance. Pathways analysis identified ribosome biogenesis and membrane estrogen-receptor signaling enriched in stem cells with NF-ĸB signaling enriched in progenitors; activities that were biologically confirmed. Further, bioassays identified heightened autophagy flux and reduced metabolism in stem cells relative to progenitors. These approaches similarly identified stem-like cells from prostate cancer specimens and prostate, breast and colon cancer cell lines suggesting wide applicability. Together, the present studies isolate and identify unique characteristics of normal human prostate stem cells and uncover processes that maintain stem cell homeostasis in the prostate gland.

  15. Bone marrow derived mesenchymal stem cells incorporate into the prostate during regrowth.

    Directory of Open Access Journals (Sweden)

    Veronica R Placencio

    2010-09-01

    Full Text Available Prostate cancer recurrence involves increased growth of cancer epithelial cells, as androgen dependent prostate cancer progresses to castrate resistant prostate cancer (CRPC following initial therapy. Understanding CRPC prostate regrowth will provide opportunities for new cancer therapies to treat advanced disease.Elevated chemokine expression in the prostate stroma of a castrate resistant mouse model, Tgfbr2(fspKO, prompted us to look at the involvement of bone marrow derived cells (BMDCs in prostate regrowth. We identified bone marrow cells recruited to the prostate in GFP-chimeric mice. A dramatic increase in BMDC recruitment for prostate regrowth occurred three days after exogenous testosterone implantation. Recruitment led to incorporation of BMDCs within the prostate epithelia. Immunofluorescence staining suggested BMDCs in the prostate coexpressed androgen receptor; p63, a basal epithelial marker; and cytokeratin 8, a luminal epithelial marker. A subset of the BMDC population, mesenchymal stem cells (MSCs, were specifically found to be incorporated in the prostate at its greatest time of remodeling. Rosa26 expressing MSCs injected into GFP mice supported MSC fusion with resident prostate epithelial cells through co-localization of β-galactosidase and GFP during regrowth. In a human C4-2B xenograft model of CRPC, MSCs were specifically recruited. Injection of GFP-labeled MSCs supported C4-2B tumor progression by potentiating canonical Wnt signaling. The use of MSCs as a targeted delivery vector for the exogenously expressed Wnt antagonist, secreted frizzled related protein-2 (SFRP2, reduced tumor growth, increased apoptosis and potentiated tumor necrosis.Mesenchymal stem cells fuse with prostate epithelia during the process of prostate regrowth. MSCs recruited to the regrowing prostate can be used as a vehicle for transporting genetic information with potential therapeutic effects on castrate resistant prostate cancer, for instance by

  16. Prostate Cancer Stem-like Cells Contribute to the Development of Castration-Resistant Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Diane Ojo

    2015-11-01

    Full Text Available Androgen deprivation therapy (ADT has been the standard care for patients with advanced prostate cancer (PC since the 1940s. Although ADT shows clear benefits for many patients, castration-resistant prostate cancer (CRPC inevitably occurs. In fact, with the two recent FDA-approved second-generation anti-androgens abiraterone and enzalutamide, resistance develops rapidly in patients with CRPC, despite their initial effectiveness. The lack of effective therapeutic solutions towards CRPC largely reflects our limited understanding of the underlying mechanisms responsible for CRPC development. While persistent androgen receptor (AR signaling under castration levels of serum testosterone (<50 ng/mL contributes to resistance to ADT, it is also clear that CRPC evolves via complex mechanisms. Nevertheless, the physiological impact of individual mechanisms and whether these mechanisms function in a cohesive manner in promoting CRPC are elusive. In spite of these uncertainties, emerging evidence supports a critical role of prostate cancer stem-like cells (PCSLCs in stimulating CRPC evolution and resistance to abiraterone and enzalutamide. In this review, we will discuss the recent evidence supporting the involvement of PCSLC in CRPC acquisition as well as the pathways and factors contributing to PCSLC expansion in response to ADT.

  17. Bmi-1 is a Crucial Regulator of Prostate Stem Cell Self-Renewal and Malignant Transformation

    Science.gov (United States)

    Lukacs, Rita U.; Memarzadeh, Sanaz; Wu, Hong; Witte, Owen N.

    2011-01-01

    SUMMARY The Polycomb group transcriptional repressor Bmi-1 is often up-regulated in prostate cancer, but its functional roles in prostate stem cell maintenance and prostate cancer are unclear. Loss- and gain-of-function analysis in a prostate sphere assay indicates that Bmi-1 expression is required for self-renewal activity and maintenance of p63+ stem cells. Loss of Bmi-1 blocks the self-renewal activity induced by heightened beta-catenin signaling, suggesting that Bmi-1 is required for full activity of another self-renewal pathway. In vivo, Bmi-1 expression is necessary for normal prostate tubule regeneration. Altered self-renewal and proliferation through Bmi-1 modulation diminishes the susceptibility of prostate cells to transformation. In an in vivo prostate regeneration system, Bmi-1 inhibition protects prostate cells from FGF10 driven hyperplasia and slows the growth of aggressive Pten-deletion induced prostate cancer. We conclude that Bmi-1 is a crucial regulator of self-renewal in adult prostate cells, and plays important roles in prostate cancer initiation and progression. PMID:21112563

  18. TGF-? maintains dormancy of prostatic stem cells in the proximal region of ducts

    OpenAIRE

    Salm, Sarah N.; Patricia E Burger; Coetzee, Sandra; Goto, Ken; Moscatelli, David; Wilson, E. Lynette

    2005-01-01

    We have previously shown that prostatic stem cells are located in the proximal region of mouse prostatic ducts. Here, we show that this region responds differently to transforming growth factor (TGF)-? than the distal ductal region and that under physiological conditions androgens and TGF-? are crucial overall regulators of prostatic tissue homeostasis. This conclusion is supported by the observations showing that high levels of TGF-? signaling are present in the quiescent proximal region of ...

  19. Molecular signatures of the primitive prostate stem cell niche reveal novel mesenchymal-epithelial signaling pathways.

    Directory of Open Access Journals (Sweden)

    Roy Blum

    2010-09-01

    Full Text Available Signals between stem cells and stroma are important in establishing the stem cell niche. However, very little is known about the regulation of any mammalian stem cell niche as pure isolates of stem cells and their adjacent mesenchyme are not readily available. The prostate offers a unique model to study signals between stem cells and their adjacent stroma as in the embryonic prostate stem cell niche, the urogenital sinus mesenchyme is easily separated from the epithelial stem cells. Here we investigate the distinctive molecular signals of these two stem cell compartments in a mammalian system.We isolated fetal murine urogenital sinus epithelium and urogenital sinus mesenchyme and determined their differentially expressed genes. To distinguish transcripts that are shared by other developing epithelial/mesenchymal compartments from those that pertain to the prostate stem cell niche, we also determined the global gene expression of epidermis and dermis of the same embryos. Our analysis indicates that several of the key transcriptional components that are predicted to be active in the embryonic prostate stem cell niche regulate processes such as self-renewal (e.g., E2f and Ap2, lipid metabolism (e.g., Srebp1 and cell migration (e.g., Areb6 and Rreb1. Several of the enriched promoter binding motifs are shared between the prostate epithelial/mesenchymal compartments and their epidermis/dermis counterparts, indicating their likely relevance in epithelial/mesenchymal signaling in primitive cellular compartments. Based on differential gene expression we also defined ligand-receptor interactions that may be part of the molecular interplay of the embryonic prostate stem cell niche.We provide a comprehensive description of the transcriptional program of the major regulators that are likely to control the cellular interactions in the embryonic prostatic stem cell niche, many of which may be common to mammalian niches in general. This study provides a

  20. Molecular signatures of the primitive prostate stem cell niche reveal novel mesenchymal-epithelial signaling pathways.

    Science.gov (United States)

    Blum, Roy; Gupta, Rashmi; Burger, Patricia E; Ontiveros, Christopher S; Salm, Sarah N; Xiong, Xiaozhong; Kamb, Alexander; Wesche, Holger; Marshall, Lisa; Cutler, Gene; Wang, Xiangyun; Zavadil, Jiri; Moscatelli, David; Wilson, E Lynette

    2010-09-30

    Signals between stem cells and stroma are important in establishing the stem cell niche. However, very little is known about the regulation of any mammalian stem cell niche as pure isolates of stem cells and their adjacent mesenchyme are not readily available. The prostate offers a unique model to study signals between stem cells and their adjacent stroma as in the embryonic prostate stem cell niche, the urogenital sinus mesenchyme is easily separated from the epithelial stem cells. Here we investigate the distinctive molecular signals of these two stem cell compartments in a mammalian system. We isolated fetal murine urogenital sinus epithelium and urogenital sinus mesenchyme and determined their differentially expressed genes. To distinguish transcripts that are shared by other developing epithelial/mesenchymal compartments from those that pertain to the prostate stem cell niche, we also determined the global gene expression of epidermis and dermis of the same embryos. Our analysis indicates that several of the key transcriptional components that are predicted to be active in the embryonic prostate stem cell niche regulate processes such as self-renewal (e.g., E2f and Ap2), lipid metabolism (e.g., Srebp1) and cell migration (e.g., Areb6 and Rreb1). Several of the enriched promoter binding motifs are shared between the prostate epithelial/mesenchymal compartments and their epidermis/dermis counterparts, indicating their likely relevance in epithelial/mesenchymal signaling in primitive cellular compartments. Based on differential gene expression we also defined ligand-receptor interactions that may be part of the molecular interplay of the embryonic prostate stem cell niche. We provide a comprehensive description of the transcriptional program of the major regulators that are likely to control the cellular interactions in the embryonic prostatic stem cell niche, many of which may be common to mammalian niches in general. This study provides a comprehensive source

  1. Selective inhibitory effect of HPMA copolymer-cyclopamine conjugate on prostate cancer stem cells.

    Science.gov (United States)

    Zhou, Yan; Yang, Jiyuan; Kopeček, Jindřich

    2012-02-01

    Improved treatments for prostate cancer are in great need to overcome lethal recurrence and metastasis. Targeting the tumorigenic cancer stem cells (CSCs) with self-renewal and differentiation capacity appears to be a promising strategy. Blockade of the hedgehog (Hh) signaling pathway, an important pathway involved in stem cell self-renewal, by cyclopamine leads to long-term prostate cancer regression without recurrence, strongly suggesting the connection between Hh pathway and prostate CSCs. Here we designed an HPMA (N-(2-hydroxypropyl)methacrylamide)-based cyclopamine delivery system as a CSC-selective macromolecular therapeutics with improved drug solubility and decreased systemic toxicity. To this end, HPMA and N-methacryloylglycylphenylalanylleucylglycyl thiazolidine-2-thione were copolymerized using the RAFT (reversible addition-fragmentation chain transfer) process, followed by polymer-analogous attachment of cyclopamine. The selectivity of the conjugate toward CSCs was evaluated on RC-92a/hTERT cells, the human prostate cancer epithelial cells with human telomerase reverse transcriptase transduction. The use of RC-92a/hTERT cells as an in vitro CSC model was validated by stem cell marker expression and prostasphere culture. The bioactivity of cyclopamine was retained after conjugation to the polymer. Furthermore, HPMA polymer-conjugated cyclopamine showed anti-CSC efficacy on RC-92a/hTERT cells as evaluated by decreased stem cell marker expression and CSC viability. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Activation of c-MET induces a Stem-Like phenotype in human prostate cancer

    NARCIS (Netherlands)

    G.J.H.L. Leenders (Geert); R. Sookhlall (Rajesh); W.J. Teubel (Wilma); C.M.A. Ridder (Corrina); S. Reneman (Suzanne); A. Sacchetti (Andrea); K.J. Vissers (Kees); W.M. van Weerden (Wytske); G.W. Jenster (Guido)

    2011-01-01

    textabstractProstate cancer consists of secretory cells and a population of immature cells. The function of immature cells and their mutual relation with secretory cells are still poorly understood. Immature cells either have a hierarchical relation to secretory cells (stem cell model) or represent

  3. The Basal Cell Marker p63 and Prostate Stem Cells

    National Research Council Canada - National Science Library

    Signoretti, Sabina

    2002-01-01

    ...(s) involved in prostate carcinogenesis. The p53-homologue p63 is selectively expressed in the basal cell compartment of a variety of epithelial tissues and p63 deficient mice show severe defects in the development of epithelial organs...

  4. The Basal Cell Marker p63 and Prostate Stem Cells

    National Research Council Canada - National Science Library

    Signoretti, Sabina

    2003-01-01

    ...(s) involved in prostate carcinogenesis. The p53-homologue p63 is selectively expressed in the basal cell compartment of a variety of epithelial tissues and p63 deficient mice show severe defects in the development of epithelial organs...

  5. The Basal Cell Marker p63 and Prostate Stem Cells

    National Research Council Canada - National Science Library

    Signoretti, Sabina

    2004-01-01

    ...(s) involved in prostate carcinogenesis. The p53-homologue p63 is selectively expressed in the basal cell compartment of a variety of epithelial tissues and p63 deficient mice show severe defects in the development of epithelial organs...

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

    Science.gov (United States)

    2015-05-01

    demonstrating the identification of prostate CSCs from primary human tissue with subsequent illustration that the proffered CSC is tumor-initiating in...noted to be positive for chromogranin A and vice versa (for illustration , an area with abundant NE cells are shown in Fig. 6A). In order to definitively...Res. 1993; 53:2853–2857. Hobisch A, Culig Z, Radmayr C, Bartsch G, Klocker H, Hittmair A. Distant metastases from prostatic carcinoma express androgen

  7. Notch and TGFβ Form a Reciprocal Positive Regulatory Loop that Suppresses Murine Prostate Basal Stem/Progenitor Cell Activity

    Science.gov (United States)

    Valdez, Joseph M; Zhang, Li; Su, Qingtai; Dakhova, Olga; Zhang, Yiqun; Shahi, Payam; Spencer, David M; Creighton, Chad J; Ittmann, Michael M; Xin, Li

    2012-01-01

    Summary The role of Notch signaling in the maintenance of adult murine prostate epithelial homeostasis remains unclear. We found that Notch ligands are mainly expressed within the basal cell lineage, while active Notch signaling is detected in both the prostate basal and luminal cell lineages. Disrupting the canonical Notch effector RBP-J impairs the differentiation of prostate basal stem cells and increases their proliferation in vitro and in vivo, but does not affect luminal cell biology. Conversely, ectopic Notch activation in adult prostates results in a decrease of basal cell number and luminal cell hyper-proliferation. TGFβ dominates over Notch signaling and overrides Notch ablation-induced proliferation of prostate basal cells. However, Notch confers sensitivity and positive feedback by up-regulating a plethora of TGFβ signaling components including TGFβRI. These findings reveal crucial roles of the self-enforced positive reciprocal regulatory loop between TGFβ and Notch in maintaining prostate basal stem cell dormancy. PMID:23122291

  8. Activation of c-MET induces a stem-like phenotype in human prostate cancer.

    Directory of Open Access Journals (Sweden)

    Geert J L H van Leenders

    Full Text Available Prostate cancer consists of secretory cells and a population of immature cells. The function of immature cells and their mutual relation with secretory cells are still poorly understood. Immature cells either have a hierarchical relation to secretory cells (stem cell model or represent an inducible population emerging upon appropriate stimulation of differentiated cells. Hepatocyte Growth Factor (HGF receptor c-MET is specifically expressed in immature prostate cells. Our objective is to determine the role of immature cells in prostate cancer by analysis of the HGF/c-MET pathway.Gene-expression profiling of DU145 prostate cancer cells stimulated with HGF revealed induction of a molecular signature associated with stem cells, characterized by up-regulation of CD49b, CD49f, CD44 and SOX9, and down-regulation of CD24 ('stem-like signature'. We confirmed the acquisition of a stem-like phenotype by quantitative PCR, FACS analysis and Western blotting. Further, HGF led to activation of the stem cell related Notch pathway by up-regulation of its ligands Jagged-1 and Delta-like 4. Small molecules SU11274 and PHA665752 targeting c-MET activity were both able to block the molecular and biologic effects of HGF. Knock-down of c-MET by shRNA infection resulted in significant reduction and delay of orthotopic tumour-formation in male NMRI mice. Immunohistochemical analysis in prostatectomies revealed significant enrichment of c-MET positive cells at the invasive front, and demonstrated co-expression of c-MET with stem-like markers CD49b and CD49f.In conclusion, activation of c-MET in prostate cancer cells induced a stem-like phenotype, indicating a dynamic relation between differentiated and stem-like cells in this malignancy. Its mediation of efficient tumour-formation in vivo and predominant receptor expression at the invasive front implicate that c-MET regulates tumour infiltration in surrounding tissues putatively by acquisition of a stem-like phenotype.

  9. Adipose Stem Cell-Based Therapeutic Targeting of Residual Androgens in African Americans With Bone-Metastatic Prostate Cancer

    Science.gov (United States)

    2014-09-01

    Hereditary prostate cancer : epidemiologic and clinical features. J Urol., 150(3):797-802, 1993. 12. Boring, C. C. Cancer StatistiAC. (1991) CA...Ross K, et al. Increased expression of genes converting adrenal androgens to testosterone in androgen-independent prostate cancer . Cancer Res 2006;66(5):2815–2825. [PubMed: 16510604]. 12 ...Adipose Stem Cell-Based Therapeutic Targeting of Residual Androgens in African Americans With Bone-Metastatic Prostate Cancer PRINCIPAL

  10. Mesenchymal stem cells expressing therapeutic genes induce autochthonous prostate tumour regression.

    Science.gov (United States)

    Abrate, Alberto; Buono, Roberta; Canu, Tamara; Esposito, Antonio; Del Maschio, Alessandro; Lucianò, Roberta; Bettiga, Arianna; Colciago, Giorgia; Guazzoni, Giorgio; Benigni, Fabio; Hedlund, Petter; Altaner, Cestmir; Montorsi, Francesco; Cavarretta, Ilaria T R

    2014-09-01

    Mesenchymal stem cells (MSC) as vehicles of therapeutic genes represent a unique tool to activate drugs within a neoplastic mass due to their property to home and engraft into tumours. In particular, MSC expressing the cytosine deaminase::uracil phosphoribosyltransferase (CD-MSC) have been previously demonstrated to inhibit growth of subcutaneous prostate cancer xenografts thanks to their ability to convert the non-toxic 5-fluorocytosine into the antineoplastic 5-fluorouracil. Since both the immune system and the tumour microenvironment play a crucial role in directing cancer progression, in order to advance towards clinical applications, we tested the therapeutic potential of this approach on animal models that develop autochthonous prostate cancer and preserve an intact immune system. As cell vectors, we employed adipose-tissue and bone-marrow MSC. CD-MSC toxicity on murine prostate cancer cells and tumour tropism were verified in vitro and ex-vivo before starting the preclinical studies. Magnetic Resonance Imaging was utilised to follow orthotopic tumour progression. We demonstrated that intravenous injections of CD-MSC cells, followed by intraperitoneal administration of 5-fluorocytosine, caused tumour regression in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model, which develops aggressive and spontaneous prostate cancer. These results add new insights to the therapeutic potential of specifically engineered MSC in prostate cancer disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Mesenchymal Stem Cell Based Therapy for Prostate Cancer

    Science.gov (United States)

    2015-11-01

    14 4 1. Introduction Prostate cancer (PCa) is the second most common cancer and the second leading cause of cancer- related deaths in American men...internalization by MSCs (red (DiI) - MPs, green ( cholera toxin) - cell membrane, blue (Hoechst) - cell nucleus). (d) To assess drug release from G114 MP-loaded

  12. Prostate Cancer Stem Cells and Nanotechnology: A Focus on Wnt Signaling.

    Science.gov (United States)

    Qin, Wei; Zheng, Yongjiang; Qian, Bin-Zhi; Zhao, Meng

    2017-01-01

    Prostate cancer is the most common cancer among men worldwide. However, current treatments for prostate cancer patients in advanced stage often fail because of relapse. Prostate cancer stem cells (PCSCs) are resistant to most standard therapies, and are considered to be a major mechanism of cancer metastasis and recurrence. In this review, we summarized current understanding of PCSCs and their self-renewal signaling pathways with a specific focus on Wnt signaling. Although multiple Wnt inhibitors have been developed to target PCSCs, their application is still limited by inefficient delivery and toxicity in vivo. Recently, nanotechnology has opened a new avenue for cancer drug delivery, which significantly increases specificity and reduces toxicity. These nanotechnology-based drug delivery methods showed great potential in targeting PCSCs. Here, we summarized current advancement of nanotechnology-based therapeutic strategies for targeting PCSCs and highlighted the challenges and perspectives in designing future therapies to eliminate PCSCs.

  13. Epithelial to mesenchymal transition is mechanistically linked with stem cell signatures in prostate cancer cells.

    Directory of Open Access Journals (Sweden)

    Dejuan Kong

    Full Text Available BACKGROUND: Current management of patients diagnosed with prostate cancer (PCa is very effective; however, tumor recurrence with Castrate Resistant Prostate Cancer (CRPC and subsequent metastasis lead to poor survival outcome, suggesting that there is a dire need for novel mechanistic understanding of tumor recurrence, which would be critical for designing novel therapies. The recurrence and the metastasis of PCa are tightly linked with the biology of prostate cancer stem cells or cancer-initiating cells that is reminiscent of the acquisition of Epithelial to Mesenchymal Transition (EMT phenotype. Increasing evidence suggests that EMT-type cells share many biological characteristics with cancer stem-like cells. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we found that PCa cells with EMT phenotype displayed stem-like cell features characterized by increased expression of Sox2, Nanog, Oct4, Lin28B and/or Notch1, consistent with enhanced clonogenic and sphere (prostasphere-forming ability and tumorigenecity in mice, which was associated with decreased expression of miR-200 and/or let-7 family. Reversal of EMT by re-expression of miR-200 inhibited prostasphere-forming ability of EMT-type cells and reduced the expression of Notch1 and Lin28B. Down-regulation of Lin28B increased let-7 expression, which was consistent with repressed self-renewal capability. CONCLUSIONS/SIGNIFICANCE: These results suggest that miR-200 played a pivotal role in linking the characteristics of cancer stem-like cells with EMT-like cell signatures in PCa. Selective elimination of cancer stem-like cells by reversing the EMT phenotype to Mesenchymal-Epithelial Transition (MET phenotype using novel agents would be useful for the prevention of tumor recurrence especially by eliminating those cells that are the "Root Cause" of tumor development and recurrence.

  14. Expression of stem cell marker CD44 in prostate cancer biopsies predicts cancer grade in radical prostatectomy specimens.

    Science.gov (United States)

    Korski, K; Malicka-Durczak, A; Bręborowicz, J

    2014-12-01

    Cancer stem cells play an important role in development and progression of many cancer types including prostate adenocarcinoma. We used a stem cell marker CD44 to evaluate the prevalence of prostate cancer stem cells in prostate biopsies and in matched radical prostatectomy specimens. We tested both types of specimen for the existence of a correlation between the immunohistochemical expression of CD44 and Gleason grade, pathological stage (pT) according to TNM, patient age and preoperative plasma PSA levels in 52 patients. We found a positive correlation between the expression of CD44 in cancer cells from prostate biopsies and in matched radical prostatectomy specimens. We also observed that higher level of CD44 expression in cancer cells correlated with lower Gleason score, both in prostate biopsies and in radical prostatectomies. To the best of our knowledge we showed for the first time, that the level of CD44 expression in prostate biopsies correlates with that observed in matched radical prostatectomy specimens. Since the level of CD44 expression was shown to predict a response to anti cancer therapy in several types of human tumors, CD44 assessment might support a clinical decision making process in prostate cancer patients.

  15. Epithelial cell-targeted transgene expression enables isolation of cyan fluorescent protein (CFP)-expressing prostate stem/progenitor cells.

    Science.gov (United States)

    Peng, Weidan; Bao, Yunhua; Sawicki, Janet A

    2011-10-01

    To establish a method for efficient and relatively easy isolation of a cell population containing epithelial prostate stem cells, we developed two transgenic mouse models, K5/CFP and K18/RFP. In these models, promoters of the cytokeratin 5 (Krt5) and the cytokeratin 18 (Krt18) genes regulate cyan and red fluorescent proteins (CFP and RFP), respectively. CFP and RFP reporter protein fluorescence allows for visualization of K5(+) and K18(+) epithelial cells within the cellular spatial context of the prostate gland and for their direct isolation by FACS. Using these models, it is possible to test directly the stem cell properties of prostate epithelial cell populations that are positively selected based on expression of cytoplasmic proteins, K5 and K18. After validating appropriate expression of the K5/CFP and K18/RFP transgenes in the developing and adult prostate, we demonstrate that a subset of CFP-expressing prostate cells exhibits stem cell proliferation potential and differentiation capabilities. Then, using prostate cells sorted from double transgenic mice (K5/CFP + K18/RFP), we compare RNA microarrays of sorted K5(+)K18(+) basal and K5(-)K18(+) luminal epithelial cells, and identify genes that are differentially expressed. Several genes that are over-expressed in K5(+) cells have previously been identified as potential stem cell markers. These results suggest that FACS isolation of prostate cells from these mice based on combining reporter gene fluorescence with expression of potential stem cell surface marker proteins will yield populations of cells enriched for stem cells to a degree that has not been attained by using cell surface markers alone.

  16. Multipotent Basal Stem Cells, Maintained in Localized Proximal Niches, Support Directed Long-Ranging Epithelial Flows in Human Prostates

    Directory of Open Access Journals (Sweden)

    Mohammad Moad

    2017-08-01

    Full Text Available Sporadic mitochondrial DNA mutations serve as clonal marks providing access to the identity and lineage potential of stem cells within human tissues. By combining quantitative clonal mapping with 3D reconstruction of adult human prostates, we show that multipotent basal stem cells, confined to discrete niches in juxta-urethral ducts, generate bipotent basal progenitors in directed epithelial migration streams. Basal progenitors are then dispersed throughout the entire glandular network, dividing and differentiating to replenish the loss of apoptotic luminal cells. Rare lineage-restricted luminal stem cells, and their progeny, are confined to proximal ducts and provide only minor contribution to epithelial homeostasis. In situ cell capture from clonal maps identified delta homolog 1 (DLK1 enrichment of basal stem cells, which was validated in functional spheroid assays. This study establishes significant insights into niche organization and function of prostate stem and progenitor cells, with implications for disease.

  17. Berberis libanotica Ehrenb extract shows anti-neoplastic effects on prostate cancer stem/progenitor cells.

    Science.gov (United States)

    El-Merahbi, Rabih; Liu, Yen-Nien; Eid, Assaad; Daoud, Georges; Hosry, Leina; Monzer, Alissar; Mouhieddine, Tarek H; Hamade, Aline; Najjar, Fadia; Abou-Kheir, Wassim

    2014-01-01

    Cancer stem cells (CSCs), including those of advanced prostate cancer, are a suggested reason for tumor resistance toward conventional tumor therapy. Therefore, new therapeutic agents are urgently needed for targeting CSCs. Despite the minimal understanding of their modes of action, natural products and herbal therapies have been commonly used in the prevention and treatment of many cancers. Berberis libanotica Ehrenb (BLE) is a plant rich in alkaloids which may possess anti-cancer activity and a high potential for eliminating CSCs. We tested the effect of BLE on prostate cancer cells and our data indicated that this extract induced significant reduction in cell viability and inhibited the proliferation of human prostate cancer cell lines (DU145, PC3 and 22Rv1) in a dose- and time-dependent manner. BLE extract induced a perturbation of the cell cycle, leading to a G0-G1 arrest. Furthermore, we noted 50% cell death, characterized by the production of high levels of reactive oxidative species (ROS). Inhibition of cellular migration and invasion was also achieved upon treatment with BLE extract, suggesting a role in inhibiting metastasis. Interestingly, BLE extract had a major effect on CSCs. Cells were grown in a 3D sphere-formation assay to enrich for a population of cancer stem/progenitor cells. Our results showed a significant reduction in sphere formation ability. Three rounds of treatment with BLE extract were sufficient to eradicate the self-renewal ability of highly resistant CSCs. In conclusion, our results suggest a high therapeutic potential of BLE extract in targeting prostate cancer and its CSCs.

  18. Berberis libanotica Ehrenb extract shows anti-neoplastic effects on prostate cancer stem/progenitor cells.

    Directory of Open Access Journals (Sweden)

    Rabih El-Merahbi

    Full Text Available Cancer stem cells (CSCs, including those of advanced prostate cancer, are a suggested reason for tumor resistance toward conventional tumor therapy. Therefore, new therapeutic agents are urgently needed for targeting CSCs. Despite the minimal understanding of their modes of action, natural products and herbal therapies have been commonly used in the prevention and treatment of many cancers. Berberis libanotica Ehrenb (BLE is a plant rich in alkaloids which may possess anti-cancer activity and a high potential for eliminating CSCs. We tested the effect of BLE on prostate cancer cells and our data indicated that this extract induced significant reduction in cell viability and inhibited the proliferation of human prostate cancer cell lines (DU145, PC3 and 22Rv1 in a dose- and time-dependent manner. BLE extract induced a perturbation of the cell cycle, leading to a G0-G1 arrest. Furthermore, we noted 50% cell death, characterized by the production of high levels of reactive oxidative species (ROS. Inhibition of cellular migration and invasion was also achieved upon treatment with BLE extract, suggesting a role in inhibiting metastasis. Interestingly, BLE extract had a major effect on CSCs. Cells were grown in a 3D sphere-formation assay to enrich for a population of cancer stem/progenitor cells. Our results showed a significant reduction in sphere formation ability. Three rounds of treatment with BLE extract were sufficient to eradicate the self-renewal ability of highly resistant CSCs. In conclusion, our results suggest a high therapeutic potential of BLE extract in targeting prostate cancer and its CSCs.

  19. Association of rs2294008 and rs9297976 Polymorphisms in PSCA Gene with Gastric Cancer Susceptibility in Uzbekistan

    Directory of Open Access Journals (Sweden)

    Shahlo Turdikulova

    2016-12-01

    Conclusion: Our findings support that PSCA rs2294008 and rs9297976 polymorphism may contribute to the susceptibility to gastric cancer. Genotyping of these polymorphisms can potentially be recommended as one of the criteria for identification of high risk groups for gastric cancer development in Uzbekistan.

  20. LIGHT: A Novel Immunotherapy for Primary and Metastatic Prostate Cancer

    Science.gov (United States)

    2015-11-01

    show in various tumor models to induce tumor regression and tumor immunogencity. However, the models are based on transplanted tumors that express...have provided the first evidence that LIGHT- induced T cells are specific for at least one relevant prostate expressed self- antigen, PSCA. We have also...to the loss of testosterone (including fatigue, decreased sexual desire, weight gain, loss of muscle mass and osteoporosis ) and the well- known

  1. Multifunctional PSCA Antibody Fragments for PET and Optical Prostate Cancer Imaging

    Science.gov (United States)

    2016-10-01

    cys-minibodies, described above. What opportunities for training and professional development has the project provided? Nothing to report. How...tumors with excellent visualization by PET imaging. Recently, dual -labeling (with radionuclide and fluorescent dye) of the cys- minibody has been...mouse models Major Task 6. Development and evaluation of singly labeled and optimized optical probes for surgery Major Task 7. Development of dual

  2. Genetic variant as a marker for bladder cancer therapy

    Science.gov (United States)

    Patients who have inherited a specific common genetic variant develop bladder cancer tumors that strongly express a protein known as prostate stem cell antigen (PSCA), which is also expressed in many pancreatic and prostate tumors, according to research a

  3. Bone Marrow-derived Mesenchymal Stem Cells (MSCs) as a Selective Delivery Vehicle for a PSA-Activated Protoxin for Advanced Prostate Cancer

    Science.gov (United States)

    2014-04-01

    and malignant prostate. A heuristic model of prostate carcinogenesis suggests that the normal gland progresses through proliferative inflammatory...Review W N Brennen et al. MSCs and the inflammatory prostate 20 :5 R287marrow, fat, spleen and thymus . Bone 40 382–390. (doi:10.1016/j.bone...stem cells derived from bone marrow, fat, spleen and thymus . Bone. 2007; 40(2):382-390. 13. Hermann A, List C, Habisch HJ, Vukicevic V, Ehrhart

  4. Enrichment of prostate cancer stem-like cells from human prostate cancer cell lines by culture in serum-free medium and chemoradiotherapy.

    Science.gov (United States)

    Wang, Lei; Huang, Xing; Zheng, Xinmin; Wang, Xinghuan; Li, Shiwen; Zhang, Lin; Yang, Zhonghua; Xia, Zhiping

    2013-01-01

    The discovery of rare subpopulations of cancer stem cells (CSCs) has created a new focus in cancer research. As CSCs demonstrate resistance to chemoradiation therapy relative to other cancer cells, this allows the enrichment of CSC populations by killing apoptosis-susceptible cancer cells. In this study, three commonly used human prostate cancer (PCa) cell lines (DU145, PC-3 and LNCaP) were examined for their expression of the putative stem cell markers CD133 and CD44 via flow cytometric analysis. Under normal culture conditions, CD133(+)/CD44(+) cells were only present in the DU145 cell line, and comprised only a minor percentage (0.1% ± 0.01%) of the total population. However, the proportion of these CD133(+)/CD44(+) prostate CSCs could be increased in these cell lines via culture in serum-free medium (SFM), or through chemotherapy or radiotherapy. Indeed, after culture in SFM, the proportion of CD133(+)/CD44(+) cells in DU145 and PC-3 had increased to 10.3% and 3.0%, respectively. Moreover, the proportion had increased to 9.8% enriched by chemotherapy and 3.5% by radiotherapy in DU145. Colony-formation tests, cell invasion assays, and tumor xenografts in BALB/c nude mice were used to evaluate the stem cell properties of CD133(+)/CD44(+) PCa cells that were isolated via fluorescence-activated cell sorting (FACS). CD133(+)/CD44(+) cells had an enhanced colony-formation capability and invasive ability in vitro, and displayed greater tumorigenic properties in vivo. These results demonstrate the presence of CD133(+)/CD44(+) prostate CSCs in established PCa cell lines and that populations of these cells can be enriched by culture in SFM or chemoradiotherapy. Finding novel therapies to override chemoradiation resistance in the prostate CSCs is the key to improve long-term results in PCa management.

  5. Sulforaphane and TRAIL induce a synergistic elimination of advanced prostate cancer stem-like cells.

    Science.gov (United States)

    Labsch, Sabrina; Liu, Li; Bauer, Nathalie; Zhang, Yiyao; Aleksandrowicz, Ewa; Gladkich, Jury; Schönsiegel, Frank; Herr, Ingrid

    2014-05-01

    Advanced androgen-independent prostate cancer (AIPC) is an aggressive malignancy with a poor prognosis. Apoptosis-resistant cancer stem cells (CSCs) have been identified in AIPC and are not eliminated by current therapeutics. Novel therapeutic options, which are currently being evaluated in patient studies, include TRAIL and the broccoli-derived isothiocyanate sulforaphane. Although neither agent targets normal cells, TRAIL induces apoptosis in most cancer cells, and sulforaphane eliminates CSCs. In this study, the established AIPC cell lines DU145 and PC3, with enriched CSC features, and primary patient-derived prostate CSCs were treated with sulforaphane and recombinant soluble TRAIL. We examined the effects of these drugs on NF-κB activity, self-renewal and differentiation potential, and stem cell signaling via spheroid- and colony-forming assays, FACS and western blot analyses, immunohistochemistry, and an antibody protein array in vitro and after xenotransplantation. We largely found a stronger effect of sulforaphane on CSC properties compared to TRAIL, though the agents acted synergistically when applied in combination. This was associated with the inhibition of TRAIL-induced NF-κB binding; CXCR4, Jagged1, Notch 1, SOX 2, and Nanog expression; ALDH1 activity inhibition; and the elimination of differentiation and self-renewal potential. In vivo, tumor engraftment and tumor growth were strongly inhibited, without the induction of liver necrosis or other obvious side effects. These findings suggest that sulforaphane shifts the balance from TRAIL-induced survival signals to apoptosis and thus explains the observed synergistic effect. A nutritional strategy for high sulforaphane intake may target the cancer-specific activity of TRAIL in CSCs.

  6. The molecular signature of the stroma response in prostate cancer-induced osteoblastic bone metastasis highlights expansion of hematopoietic and prostate epithelial stem cell niches.

    Directory of Open Access Journals (Sweden)

    Berna C Özdemir

    Full Text Available The reciprocal interaction between cancer cells and the tissue-specific stroma is critical for primary and metastatic tumor growth progression. Prostate cancer cells colonize preferentially bone (osteotropism, where they alter the physiological balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption, and elicit prevalently an osteoblastic response (osteoinduction. The molecular cues provided by osteoblasts for the survival and growth of bone metastatic prostate cancer cells are largely unknown. We exploited the sufficient divergence between human and mouse RNA sequences together with redefinition of highly species-specific gene arrays by computer-aided and experimental exclusion of cross-hybridizing oligonucleotide probes. This strategy allowed the dissection of the stroma (mouse from the cancer cell (human transcriptome in bone metastasis xenograft models of human osteoinductive prostate cancer cells (VCaP and C4-2B. As a result, we generated the osteoblastic bone metastasis-associated stroma transcriptome (OB-BMST. Subtraction of genes shared by inflammation, wound healing and desmoplastic responses, and by the tissue type-independent stroma responses to a variety of non-osteotropic and osteotropic primary cancers generated a curated gene signature ("Core" OB-BMST putatively representing the bone marrow/bone-specific stroma response to prostate cancer-induced, osteoblastic bone metastasis. The expression pattern of three representative Core OB-BMST genes (PTN, EPHA3 and FSCN1 seems to confirm the bone specificity of this response. A robust induction of genes involved in osteogenesis and angiogenesis dominates both the OB-BMST and Core OB-BMST. This translates in an amplification of hematopoietic and, remarkably, prostate epithelial stem cell niche components that may function as a self-reinforcing bone metastatic niche providing a growth support specific for osteoinductive prostate cancer cells. The induction

  7. Directed Differentiation of Human Embryonic Stem Cells into Prostate Organoids In Vitro and its Perturbation by Low-Dose Bisphenol A Exposure.

    Directory of Open Access Journals (Sweden)

    Esther L Calderon-Gierszal

    Full Text Available Studies using rodent and adult human prostate stem-progenitor cell models suggest that developmental exposure to the endocrine disruptor Bisphenol-A (BPA can predispose to prostate carcinogenesis with aging. Unknown at present is whether the embryonic human prostate is equally susceptible to BPA during its natural developmental window. To address this unmet need, we herein report the construction of a pioneer in vitro human prostate developmental model to study the effects of BPA. The directed differentiation of human embryonic stem cells (hESC into prostatic organoids in a spatial system was accomplished with precise temporal control of growth factors and steroids. Activin-induced definitive endoderm was driven to prostate specification by combined exposure to WNT10B and FGF10. Matrigel culture for 20-30 days in medium containing R-Spondin-1, Noggin, EGF, retinoic acid and testosterone was sufficient for mature prostate organoid development. Immunofluorescence and gene expression analysis confirmed that organoids exhibited cytodifferentiation and functional properties of the human prostate. Exposure to 1 nM or 10 nM BPA throughout differentiation culture disturbed early morphogenesis in a dose-dependent manner with 1 nM BPA increasing and 10 nM BPA reducing the number of branched structures formed. While differentiation of branched structures to mature organoids seemed largely unaffected by BPA exposure, the stem-like cell population increased, appearing as focal stem cell nests that have not properly entered lineage commitment rather than the rare isolated stem cells found in normally differentiated structures. These findings provide the first direct evidence that low-dose BPA exposure targets hESC and perturbs morphogenesis as the embryonic cells differentiate towards human prostate organoids, suggesting that the developing human prostate may be susceptible to disruption by in utero BPA exposures.

  8. Prostate cancer stem cells are targets of both innate and adaptive immunity and elicit tumor-specific immune responses

    OpenAIRE

    Jachetti, Elena; Mazzoleni, Stefania; Grioni, Matteo; Ricupito, Alessia; Brambillasca, Chiara; Generoso, Luca; Calcinotto, Arianna; Freschi, Massimo; Mondino, Anna; Galli, Rossella; Bellone, Matteo

    2013-01-01

    According to the cancer stem cell (CSC) theory, therapies that do not target the CSC compartment have limited, if any, chances to eradicate established tumors. While cytotoxic T lymphocytes (CTLs) have the potential to recognize and kill single neoplastic cells within a tissue, whether CSCs can be targeted by the immune system during spontaneous or vaccination-elicited responses is poorly defined. Here, we provide experimental evidence showing that CSC lines established from the prostate of t...

  9. Establishment of a dog primary prostate cancer organoid using the urine cancer stem cells.

    Science.gov (United States)

    Usui, Tatsuya; Sakurai, Masashi; Nishikawa, Shimpei; Umata, Koji; Nemoto, Yuki; Haraguchi, Tomoya; Itamoto, Kazuhito; Mizuno, Takuya; Noguchi, Shunsuke; Mori, Takashi; Iwai, Satomi; Nakagawa, Takayuki; Yamawaki, Hideyuki; Ohama, Takashi; Sato, Koichi

    2017-12-01

    Dog spontaneously develop prostate cancer (PC) like humans. Because most dogs with PC have a poor prognosis, they could be used as a translational model for advanced PC in humans. Stem cell-derived 3-D organoid culture could recapitulate organ structures and physiology. Using patient tissues, a human PC organoid culture system was established. Recent study has shown that urine cells also possess the characteristic of stem cells. However, urine cell-derived PC organoids have never been produced. Therefore, we generated PC organoids using the dog urine samples. Urine organoids were successfully generated from each dog with PC. Each organoid showed cystic structures and resembled the epithelial structures of original tissues. Expression of an epithelial cell marker, E-cadherin, and a myofibloblast marker, α-SMA, was observed in the urine organoids. The organoids also expressed a basal cell marker, CK5, and a luminal cell marker, CK8. CD49f-sorted basal cell organoids rapidly grew compared with CD24-sorted luminal cell organoids. The population of CD44-positive cells was the highest in both organoids and the original urine cells. Tumors were successfully formed with the injection of the organoids into immunodeficient mice. Treatment with a microtubule inhibitor, docetaxel, but not a cyclooxygenase inhibitor, piroxicam, and an mTOR inhibitor, rapamycin, decreased the cell viability of organoids. Treatment with a Hedgehog signal inhibitor, GANT61, increased the radiosensitivity in the organoids. These findings revealed that PC organoids using urine might become a useful tool for investigating the mechanisms of the pathogenesis and treatment of PC in dogs. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  10. Semaphorin 3 C drives epithelial-to-mesenchymal transition, invasiveness, and stem-like characteristics in prostate cells.

    Science.gov (United States)

    Tam, Kevin J; Hui, Daniel H F; Lee, Wilson W; Dong, Mingshu; Tombe, Tabitha; Jiao, Ivy Z F; Khosravi, Shahram; Takeuchi, Ario; Peacock, James W; Ivanova, Larissa; Moskalev, Igor; Gleave, Martin E; Buttyan, Ralph; Cox, Michael E; Ong, Christopher J

    2017-09-13

    Prostate cancer (PCa) is among the most commonly-occurring cancers worldwide and a leader in cancer-related deaths. Local non-invasive PCa is highly treatable but limited treatment options exist for those with locally-advanced and metastatic forms of the disease underscoring the need to identify mechanisms mediating PCa progression. The semaphorins are a large grouping of membrane-associated or secreted signalling proteins whose normal roles reside in embryogenesis and neuronal development. In this context, semaphorins help establish chemotactic gradients and direct cell movement. Various semaphorin family members have been found to be up- and down-regulated in a number of cancers. One family member, Semaphorin 3 C (SEMA3C), has been implicated in prostate, breast, ovarian, gastric, lung, and pancreatic cancer as well as glioblastoma. Given SEMA3C's roles in development and its augmented expression in PCa, we hypothesized that SEMA3C promotes epithelial-to-mesenchymal transition (EMT) and stem-like phenotypes in prostate cells. In the present study we show that ectopic expression of SEMA3C in RWPE-1 promotes the upregulation of EMT and stem markers, heightened sphere-formation, and cell plasticity. In addition, we show that SEMA3C promotes migration and invasion in vitro and cell dissemination in vivo.

  11. Radiotherapy-induced plasticity of prostate cancer mobilizes stem-like non-adherent, Erk signaling-dependent cells.

    Science.gov (United States)

    Kyjacova, L; Hubackova, S; Krejcikova, K; Strauss, R; Hanzlikova, H; Dzijak, R; Imrichova, T; Simova, J; Reinis, M; Bartek, J; Hodny, Z

    2015-06-01

    Fractionated ionizing radiation combined with surgery or hormone therapy represents the first-choice treatment for medium to high-risk localized prostate carcinoma. One of the main reasons for the failure of radiotherapy in prostate cancer is radioresistance and further dissemination of surviving cells. In this study, exposure of four metastasis-derived human prostate cancer cell lines (DU145, PC-3, LNCaP and 22RV1) to clinically relevant daily fractions of ionizing radiation (35 doses of 2 Gy) resulted in generation of two radiation-surviving populations: adherent senescent-like cells expressing common senescence-associated markers and non-adherent anoikis-resistant stem cell-like cells with active Notch signaling and expression of stem cell markers CD133, Oct-4, Sox2 and Nanog. While a subset of the radiation-surviving adherent cells resumed proliferation shortly after completion of the irradiation regimen, the non-adherent cells started to proliferate only on their reattachment several weeks after the radiation-induced loss of adhesion. Like the parental non-irradiated cells, radiation-surviving re-adherent DU145 cells were tumorigenic in immunocompromised mice. The radiation-induced loss of adhesion was dependent on expression of Snail, as siRNA/shRNA-mediated knockdown of Snail prevented cell detachment. On the other hand, survival of the non-adherent cells required active Erk signaling, as chemical inhibition of Erk1/2 by a MEK-selective inhibitor or Erk1/2 knockdown resulted in anoikis-mediated death in the non-adherent cell fraction. Notably, whereas combined inhibition of Erk and PI3K-Akt signaling triggered cell death in the non-adherent cell fraction and blocked proliferation of the adherent population of the prostate cancer cells, such combined treatment had only marginal if any impact on growth of control normal human diploid cells. These results contribute to better understanding of radiation-induced stress response and heterogeneity of human

  12. Targeting of αv-Integrins in Stem/Progenitor Cells and Supportive Microenvironment Impairs Bone Metastasis in Human Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Geertje van der Horst

    2011-06-01

    Full Text Available Acquisition of an invasive phenotype by cancer cells is a requirement for bone metastasis. Transformed epithelial cells can switch to a motile, mesenchymal phenotype by epithelial-mesenchymal transition (EMT. Recently, it has been shown that EMT is functionally linked to prostate cancer stem cells, which are not only critically involved in prostate cancer maintenance but also in bone metastasis. We showed that treatment with the non-peptide αv-integrin antagonist GLPG0187 dose-dependently increased the E-cadherin/vimentin ratio, rendering the cells a more epithelial, sessile phenotype. In addition, GLPG0187 dose-dependently diminished the size of the aldehyde dehydrogenase high subpopulation of prostate cancer cells, suggesting that αv-integrin plays an important role in maintaining the prostate cancer stem/progenitor pool. Our data show that GLPG0187 is a potent inhibitor of osteoclastic bone resorption and angiogenesis in vitro and in vivo. Real-time bioluminescent imaging in preclinical models of prostate cancer demonstrated that blocking αv-integrins by GLPG0187 markedly reduced their metastatic tumor growth according to preventive and curative protocols. Bone tumor burden was significantly lower in the preventive protocol. In addition, the number of bone metastases/mouse was significantly inhibited. In the curative protocol, the progression of bone metastases and the formation of new bone metastases during the treatment period was significantly inhibited. In conclusion, we demonstrate that targeting of integrins by GLPG0187 can inhibit the de novo formation and progression of bone metastases in prostate cancer by antitumor (including inhibition of EMT and the size of the prostate cancer stem cell population, antiresorptive, and antiangiogenic mechanisms.

  13. Induced growth inhibition, cell cycle arrest and apoptosis in CD133+/CD44+ prostate cancer stem cells by flavopiridol.

    Science.gov (United States)

    Soner, Burak Cem; Aktug, Huseyin; Acikgoz, Eda; Duzagac, Fahriye; Guven, Ummu; Ayla, Sule; Cal, Cag; Oktem, Gulperi

    2014-11-01

    Flavopiridol is a flavone that inhibits several cyclin‑dependent kinases and exhibits potent growth‑inhibitory activity, apoptosis and G1‑phase arrest in a number of human tumor cell lines. Flavopiridol is currently undergoing investigation in human clinical trials. The present study focused on the effect of flavopiridol in cell proliferation, cell cycle progression and apoptosis in prostate cancer stem cells (CSCs). Therefore, cluster of differentiation 133 (CD133)(+high)/CD44(+high) prostate CSCs were isolated from the DU145 human prostate cancer cell line. The cells were treated with flavopiridol in a dose‑ and time‑dependent manner to determine the inhibitory effect. Cell viability and proliferation were analyzed and the efficiency of flavopiridol was assessed using the sphere‑forming assay. Flavopiridol was applied to monolayer cultures of CD133(high)/CD44(high) human prostate CSCs at the following final concentrations: 100, 300, 500 and 1000 nM . The cultures were incubated for 24, 48 and 72 h. The half maximal inhibitory concentration (IC(50)) value of the drug was determined as 500 nM for monolayer cells. Dead cells were analyzed prior and subsequent to exposure to increasing flavopiridol doses. Annexin‑V and immunofluorescence analyses were performed for the evaluation of apoptotic pathways. According to the results, flavopiridol treatment caused significant growth inhibition at 500 and 1000 nM when compared to the control at 24 h. G(0)/G(1) analysis showed a statistically significant difference between 100 and 500 nM (PFlavopiridol also significantly influenced the cells in the G(2)/M phase, particularly at high‑dose treatments. Flavopiridol induced growth inhibition and apoptosis at the IC(50) dose (500 nM), resulting in a significant increase in immunofluorescence staining of caspase‑3, caspase‑8 and p53. In conclusion, the present results indicated that flavopiridol could be a useful therapeutic agent for prostate CSCs by inhibiting

  14. Prostate cancer stem-like cells proliferate slowly and resist etoposide-induced cytotoxicity via enhancing DNA damage response

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Judy [Division of Nephrology, Department of Medicine, McMaster University, Juravinski Innovation Tower, Room T3310, St. Joseph' s Hospital, 50 Charlton Ave East, Hamilton, Ontario, Canada L8S 4L8 (Canada); Father Sean O' Sullivan Research Institute, Hamilton, Ontario, Canada L8N 4A6 (Canada); The Hamilton Centre for Kidney Research (HCKR), St. Joseph' s Hamilton Healthcare, Hamilton, Ontario, Canada L8N 4A6 (Canada); Tang, Damu, E-mail: damut@mcmaster.ca [Division of Nephrology, Department of Medicine, McMaster University, Juravinski Innovation Tower, Room T3310, St. Joseph' s Hospital, 50 Charlton Ave East, Hamilton, Ontario, Canada L8S 4L8 (Canada); Father Sean O' Sullivan Research Institute, Hamilton, Ontario, Canada L8N 4A6 (Canada); The Hamilton Centre for Kidney Research (HCKR), St. Joseph' s Hamilton Healthcare, Hamilton, Ontario, Canada L8N 4A6 (Canada)

    2014-10-15

    Despite the development of chemoresistance as a major concern in prostate cancer therapy, the underlying mechanisms remain elusive. In this report, we demonstrate that DU145-derived prostate cancer stem cells (PCSCs) progress slowly with more cells accumulating in the G1 phase in comparison to DU145 non-PCSCs. Consistent with the important role of the AKT pathway in promoting G1 progression, DU145 PCSCs were less sensitive to growth factor-induced activation of AKT in comparison to non-PCSCs. In response to etoposide (one of the most commonly used chemotherapeutic drugs), DU145 PCSCs survived significantly better than non-PCSCs. In addition to etoposide, PCSCs demonstrated increased resistance to docetaxel, a taxane drug that is commonly used to treat castration-resistant prostate cancer. Etoposide produced elevated levels of γH2AX and triggered a robust G2/M arrest along with a coordinated reduction of the G1 population in PCSCs compared to non-PCSCs, suggesting that elevated γH2AX plays a role in the resistance of PCSCs to etoposide-induced cytotoxicity. We have generated xenograft tumors from DU145 PCSCs and non-PCSCs. Consistent with the knowledge that PCSCs produce xenograft tumors with more advanced features, we were able to demonstrate that PCSC-derived xenograft tumors displayed higher levels of γH2AX and p-CHK1 compared to non-PCSC-produced xenograft tumors. Collectively, our research suggests that the elevation of DNA damage response contributes to PCSC-associated resistance to genotoxic reagents. - Highlights: • Increased survival in DU145 PCSCs following etoposide-induced cytotoxicity. • PCSCs exhibit increased sensitivity to etoposide-induced DDR. • Resistance to cytotoxicity may be due to slower proliferation in PCSCs. • Reduced kinetics to growth factor induced activation of AKT in PCSCs.

  15. YAP1 regulates prostate cancer stem cell-like characteristics to promote castration resistant growth

    DEFF Research Database (Denmark)

    Jiang, Ning; Ke, Binghu; Hjort-Jensen, Kim

    2017-01-01

    Castration resistant prostate cancer (CRPC) is a stage of relapse that arises after various forms of androgen ablation therapy (ADT) and causes significant morbidity and mortality. However, the mechanism underlying progression to CRPC remains poorly understood. Here, we report that YAP1, which is...

  16. HPMA copolymer-based combination therapy toxic to both prostate cancer stem/progenitor cells and differentiated cells induces durable anti-tumor effects.

    Science.gov (United States)

    Zhou, Yan; Yang, Jiyuan; Rhim, Johng S; Kopeček, Jindřich

    2013-12-28

    Current treatments for prostate cancer are still not satisfactory, often resulting in tumor regrowth and metastasis. One of the main reasons for the ineffective anti-prostate cancer treatments is the failure to deplete cancer stem-like cells (CSCs) - a subset of cancer cells with enhanced tumorigenic capacity. Thus, combination of agents against both CSCs and bulk tumor cells may offer better therapeutic benefits. Several molecules with anti-cancer stem/progenitor cell activities have been under preclinical evaluations. However, their low solubility and nonspecific toxicity limit their clinical translation. Herein, we designed a combination macromolecular therapy containing two drug conjugates: HPMA copolymer-cyclopamine conjugate (P-CYP) preferentially toxic to cancer stem/progenitor cells, and HPMA copolymer-docetaxel conjugate (P-DTX) effective in debulking the tumor mass. Both conjugates were synthesized using RAFT (reversible addition-fragmentation chain transfer) polymerization resulting in narrow molecular weight distribution. The killing effects of the two conjugates against bulk tumor cells and CSCs were evaluated in vitro and in vivo. In PC-3 or RC-92a/hTERT prostate cancer cells, P-CYP preferentially kills and impairs the function of CD133+ prostate cancer stem/progenitor cells; P-DTX was able to kill bulk tumor cells instead of CSCs. In a PC-3 xenograft mice model, combination of P-DTX and P-CYP showed the most effective and persistent tumor growth inhibitory effect. In addition, residual tumors contained less CD133+ cancer cells following combination or P-CYP treatments, indicating selective killing of cancer cells with stem/progenitor cell properties. © 2013 Elsevier B.V. All rights reserved.

  17. An enhancer from the 8q24 prostate cancer risk region is sufficient to direct reporter gene expression to a subset of prostate stem-like epithelial cells in transgenic mice

    Directory of Open Access Journals (Sweden)

    Man-Chun Ting

    2012-05-01

    Regions in the 8q24 gene desert contribute significantly to the risk of prostate cancer and other adult cancers. This region contains several DNA regions with enhancer activity in cultured cells. One such segment, histone acetylation peak 10 (AcP10, contains a risk single nucleotide polymorphism (SNP that is significantly associated with the pathogenesis of colorectal, prostate and other cancers. The mechanism by which AcP10 influences cancer risk remains unknown. Here we show that AcP10 contains a sequence that is highly conserved across terrestrial vertebrates and is capable in transgenic mice of directing reporter gene expression to a subset of prostate lumenal epithelial cells. These cells include a small population of Nkx3.1-positive cells that persist even after androgen ablation. Castration-resistant Nkx3.1-positive (CARN cells were shown by others to function both as stem cells and cells of origin of prostate cancer. Our results thus provide a mechanism by which AcP10 could influence prostate cancer risk.

  18. Nanoemulsion formulation of a novel taxoid DHA-SBT-1214 inhibits prostate cancer stem cell-induced tumor growth.

    Science.gov (United States)

    Ahmad, Gulzar; El Sadda, Rana; Botchkina, Galina; Ojima, Iwao; Egan, James; Amiji, Mansoor

    2017-10-10

    The main aim of this study was to evaluate the therapeutic efficacy of an oil-in-water nanoemulsion formulation encapsulating DHA-SBT-1214, a novel omega-3 fatty acid conjugated taxoid prodrug, against prostate cancer stem cells. Nanoemulsions of DHA-SBT-1214 (NE-DHA-SBT-1214) were prepared and characterized. In vitro delivery efficiency and cytotoxicity of NE-DHA-SBT-1214 was compared with solution formulation in PPT2 cells. In vivo studies included analysis of comparative efficacy of NE-DHA-SBT-1214 with Abraxane® and placebo nanoemulsions as well as post-treatment alternations in clonogenic and sphere-forming capabilities of the tumor cells. Qualitative intracellular uptake studies of dye encapsulated NEs by confocal imaging showed uptake by both monolayer and spheroid cultured PPT2 cells. Treatment of PPT2 cells with NE DHA-SBT-1214 (1nM-1μM for monolayer culture of cells grown on collagen-coated dishes for 48 h) induced complete cell death, showing higher efficacy as compared to the drug solution. This nanoemulsion (10nM-10μM) also showed toxicity in 3D culture of floating spheroids. Weekly intravenous administration of the NE-DHA-SBT-1214 to NOD/SCID mice bearing subcutaneous PPT2 tumor xenografts led to dramatic suppression of tumor growth compared to Abraxane® and placebo nanoemulsion formulation. Viable cells that survived from this in vivo treatment regimen were no longer able to induce floating spheroids and holoclones, whereas control and Abraxane® treated tumor cells induced a large number of both. The results show that NE-DHA-SBT-1214 possesses significant activity against prostate CD133high/CD44+/high tumor-initiating cells both in vitro and in vivo. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Using Human Stem Cells to Study the Role of the Stroma in the Initiation of Prostate Cancer

    Science.gov (United States)

    2011-03-01

    prostatic tumour stroma and hormonal carcinogenesis. The Innovative Minds in Prostate Cancer Today (IMPacT) Conference, Orlando, Florida , USA. (Poster...2001 Comparative studies of the estrogen receptors beta and alpha and the androgen receptor in normal human prostate glands, dysplasia , and in primary

  20. Therapeutic Role of Bmi-1 Inhibitors in Eliminating Prostate Tumor Stem Cells

    Science.gov (United States)

    2013-10-01

    PMC: 23308129. 27. Campbell PJ, Yachida S, Mudie LJ, Stephens PJ, Pleasance ED, Stebbings LA , Morsberger LA , Latimer C, McLaren S, Lin ML...imaging of the samexenograft embryo over time during 8 days of tumor growth.Fromday 2, notice the two sites that are outlinedwith tumor cells la ... metformin suppresses self-renewal and proliferation of trastuzumab-resis- tant tumor-initiating breast cancer stem cells. Breast Cancer Res Treat 2010;126

  1. Secreted heat shock protein 90 promotes prostate cancer stem cell heterogeneity

    OpenAIRE

    Nolan, Krystal D.; Kaur, Jasmine; Isaacs, Jennifer S.

    2016-01-01

    Heat-shock protein 90 (Hsp90), a highly conserved molecular chaperone, is frequently upregulated in tumors, and remains an attractive anti-cancer target. Hsp90 is also found extracellularly, particularly in tumor models. Although extracellular Hsp90 (eHsp90) action is not well defined, eHsp90 targeting attenuates tumor invasion and metastasis, supporting its unique role in tumor progression. We herein investigated the potential role of eHsp90 as a modulator of cancer stem-like cells (CSCs) in...

  2. Prostate cancer stem cell-targeted efficacy of a new-generation taxoid, SBT-1214 and novel polyenolic zinc-binding curcuminoid, CMC2.24.

    Directory of Open Access Journals (Sweden)

    Galina I Botchkina

    Full Text Available Prostate cancer is the second leading cause of cancer death among men. Multiple evidence suggests that a population of tumor-initiating, or cancer stem cells (CSCs is responsible for cancer development and exceptional drug resistance, representing a highly important therapeutic target. The present study evaluated CSC-specific alterations induced by new-generation taxoid SBT-1214 and a novel polyenolic zinc-binding curcuminoid, CMC2.24, in prostate CSCs.The CD133(high/CD44(high phenotype was isolated from spontaneously immortalized patient-derived PPT2 cells and highly metastatic PC3MM2 cells. Weekly treatment of the NOD/SCID mice bearing PPT2- and PC3MM3-induced tumors with the SBT-1214 led to dramatic suppression of tumor growth. Four of six PPT2 and 3 of 6 PC3MM2 tumors have shown the absence of viable cells in residual tumors. In vitro, SBT-1214 (100 nM-1 µM; for 72 hr induced about 60% cell death in CD133(high/CD44(+/high cells cultured on collagen I in stem cell medium (in contrast, the same doses of paclitaxel increased proliferation of these cells. The cytotoxic effects were increased when SBT-1214 was combined with the CMC2.24. A stem cell-specific PCR array assay revealed that this drug combination mediated massive inhibition of multiple constitutively up-regulated stem cell-related genes, including key pluripotency transcription factors. Importantly, this drug combination induced expression of p21 and p53, which were absent in CD133(high/CD44(high cells. Viable cells that survived this treatment regimen were no longer able to induce secondary spheroids, exhibited significant morphological abnormalities and died in 2-5 days.We report here that the SBT-1214 alone, or in combination with CMC2.24, possesses significant activity against prostate CD133(high/CD44(+/high tumor-initiating cells. This drug combination efficiently inhibits expression of the majority of stem cell-related genes and pluripotency transcription factors. In addition

  3. Pristimerin Inhibits Prostate Cancer Bone Metastasis by Targeting PC-3 Stem Cell Characteristics and VEGF-Induced Vasculogenesis of BM-EPCs

    Directory of Open Access Journals (Sweden)

    Shuai Huang

    2015-08-01

    Full Text Available Background/Aims: Prostate cancer (PCa is one of the most common malignant cancers and a major leading cause of cancer deaths in men. Cancer stem-like cells are shown to be highly tumorigenic, pro-angiogenic and can significantly contribute to tumor new vessel formation and bone marrow derived-EPCs (BM-EPCs are shown to recruit to the angiogenic switch in tumor growth and metastatic progression, suggesting the importance of targeting cancer stem cells (CSCs and EPCs for novel tumor therapies. Pristimerin, an active component isolated from Celastraceae and Hippocrateaceae, has shown anti-tumor effects in some cell lines in previous studies. However, the effect and mechanism of Pristimerin on CSCs and EPCs in PCa bone metastasis are not well studied. Methods: The effect of Pristimerin on PC-3 stem cell characteristics and metastasis were detected by spheroid formation, CD133 and CD44 protein expression, matrix-gel invasive assay and colony-formation assay in vitro, VEGF and pro-inflammatory cytokines expression by ELISA assay, and tumor tumorigenicity by X-ray and MR in NOD-SCID mice model in vivo. In addition, we also detected the effect of Pristimerin on VEGF-induced vasculogenesis and protein expression of BM-EPCs. Results: Pristimerin could significantly inhibit spheroid formation and protein expression of CD133 and CD44, reduce VEGF and pro-inflammation cytokines expression of PC-3 cell, and prevent the xenografted PC-3 tumor growth in the bone of nude mice. The present data also showed that Pristimerin significantly inhibited VEGF-induced vasculogenesis of BM-EPCs by suppressing the EPCs functions including proliferation, adhesion, migration, tube formation and inactivation the phosphorylation of VEGFR-2, Akt and eNOS. Conclusion: These data provide evidence that Pristimerin has strong potential for development as a novel agent against prostate bone metastasis by suppressing PC-3 stem cell characteristics and VEGF-induced vasculogenesis of BM-EPCs.

  4. Comparative characterization of stem cell marker expression, metabolic activity and resistance to doxorubicin in adherent and spheroid cells derived from the canine prostate adenocarcinoma cell line CT1258.

    Science.gov (United States)

    Liu, Wen; Moulay, Mohammed; Willenbrock, Saskia; Roolf, Catrin; Junghanss, Christian; Ngenazahayo, Anaclet; Nolte, Ingo; Murua Escobar, Hugo

    2015-04-01

    Canine prostate cancer represents a spontaneous animal model for the human counterpart. Cells with stem cell-like character are considered to play a major role in therapeutic resistance and tumor relapse. Thus, the identification of markers allowing for recognition and characterization of these cells is essential. Expression of 12 stem cell marker genes in the canine prostate cancer cell line CT1258 and spheroid cells generated from these was analyzed by quantitative real-time PCR. In CT1258 and the generated spheroid cells, CD44 and CD133 expression was analyzed by flow cytometry, as well as proliferation and doxorubicin resistance. Integrin alpha-6 (ITGA6) expression and metabolic activity were significantly up-regulated in CT1258-derived spheroid cells, while doxorubicin resistance remained comparable. ITGA6 de-regulation and metabolic activity appear to be characteristic of the generated spheres, indicating potential intervention targets. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  5. Curcumin suppresses proliferation and in vitro invasion of human prostate cancer stem cells by ceRNA effect of miR-145 and lncRNA-ROR.

    Science.gov (United States)

    Liu, Te; Chi, Huiying; Chen, Jiulin; Chen, Chuan; Huang, Yongyi; Xi, Hao; Xue, Jun; Si, Yibing

    2017-10-05

    Many studies have demonstrated that curcumin can effectively inhibit the proliferation, invasion, and tumorigenesis of prostate cancer cells in vitro and in vivo. In this study, CD44+/CD133+ human prostate cancer stem cells (HuPCaSCs) were isolated from the prostate cancer cell lines Du145 and 22RV1. Curcumin treatment of these cells resulted in the inhibition of in vitro proliferation and invasion, and cell cycle arrest. The expression levels of cell cycle proteins (Ccnd1 and Cdk4) and stem cell markers (Oct4, CD44, and CD133) were decreased in curcumin-treated HuPCaSCs. Microarray analysis and northern blotting assays indicated that miR-145 was overexpressed in curcumin-treated HuPCaSCs. Insights of the mechanism of competitive endogenous RNAs (ceRNAs) were gained from bioinformatic analysis, bioinformatics analysis and luciferase activity assays showed that the lncRNA-ROR and Oct4 mRNA both contain miR-145 binding sites, and Oct4 and lncRNA-ROR directly compete for microRNA binding. Curcumin induced high miR-145 expression and inhibited the expression of lncRNA-ROR. The tumorigenicity of curcumin- treated HuPCaSCs in nude mice was significantly reduced. In summary, reducing the expression of endogenous lncRNA-ROR could effectively increase the available concentration of miR-145 in HuPCaSCs, where miR-145 prevents cell proliferation by decreasing Oct4 expression. In particular, we hypothesized that lncRNA-ROR may act as a ceRNA, effectively becoming a sink for miR-145, thereby activating the derepression of core transcription factors Oct4. Thus, curcumin suppresses the proliferation, in vitro invasion, and tumorigenicity of HuPCaSCs through ceRNA effect of miR-145 and lncRNA-ROR caused. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Prostate Enlargement: Benign Prostatic Hyperplasia (BPH)

    Science.gov (United States)

    ... of the Prostate Prostate Enlargement (Benign Prostatic Hyperplasia) Prostate Enlargement (Benign Prostatic Hyperplasia) What is benign prostatic ... associated with benign prostatic hyperplasia. What is the prostate? The prostate is a walnut-shaped gland that ...

  7. STEM?!?!

    Science.gov (United States)

    Merrill, Jen

    2012-01-01

    The author's son has been an engineer since birth. He never asked "why" as a toddler, it was always "how's it work?" So that he wanted a STEM-based home education was no big surprise. In this article, the author considers what kind of curricula would work best for her complex kid.

  8. Prostate Ultrasound

    Medline Plus

    Full Text Available ... the prostate is enlarged, also known as benign prostatic hyperplasia (BPH) , with measurements acquired as needed for any ... size with caption Related Articles and Media Benign Prostatic Hyperplasia (BPH) (Enlargement of the Prostate) Prostate Cancer Ultrasound- ...

  9. JAK/STAT pathway interacts with intercellular cell adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) while prostate cancer stem cells form tumor spheroids.

    Science.gov (United States)

    Duzagac, Fahriye; Inan, Sevinc; Ela Simsek, Fatma; Acikgoz, Eda; Guven, Ummu; Khan, Shafiq A; Rouhrazi, Hadi; Oltulu, Fatih; Aktug, Huseyin; Erol, Ayse; Oktem, Gulperi

    2015-01-01

    JAK/STAT is an evolutionarily conserved pathway and very important for second messenger system. This pathway is important in malignant transformation and accumulated evidence indicates that this pathway is involved in tumorigenesis and progression of several cancers. It was possible to assume that activation of JAK/STAT pathway is associated with increase in the expressions of ICAM/1 and VCAM-1. In this study we hypothesized that when cells were maintained as spheroids or monolayers, the structure of cancer stem cells (CSCs) could show differentiation when compared with non-CSCs. DU-145 human prostate cancer cells were cultured using the Ege University molecular embryology laboratory medium supplemented wıth 10% fetal bovine serum. Clusters of differentiation 133 (CD133)(+high)/CD44(+high) prostate CSCs were isolated from the DU145 cell line by using BD FACSAria. CD133//CD44+ CSCs were cultured until confluent with 3% noble agar. The expression of these proteins in CSCs and non-CSCs was analyzed by immunohistochemistry. Different expression profiles were observed in the conventional two-dimensional (2D) and three-dimensional (3D) experimental model system when CSCs and non-CSCs were compared. Human prostate CSCs exhibited intense ICAM-1 and VCAM-1 immunoreaction when compared with non-CSCs. These findings were supported by the fact that VCAM-1 on the surface of cancer cells binds to its counterreceptor, the α4β1 integrin (also known as very-late antigen, VLA-4), on metastasis-associated macrophages, triggering VCAM-1-mediated activation of the phosphoinositide 3-kinase growth and survival pathway in cancer cells. The results of this study showed that changes in JAK/STAT pathway are related with adhesion molecules and could affect cancer progression.

  10. Two Domains of Vimentin Are Expressed on the Surface of Lymph Node, Bone and Brain Metastatic Prostate Cancer Lines along with the Putative Stem Cell Marker Proteins CD44 and CD133

    Energy Technology Data Exchange (ETDEWEB)

    Steinmetz, Nicole F. [Case Western Reserve University, Department of Biomedical Engineering, 10900 Euclid Ave, Cleveland, OH 44106 (United States); Maurer, Jochen [Sanford-Burnham, Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037 (United States); Sheng, Huiming [Torrey Pines Institute for Molecular Studies, Division of Immune Regulation, 3550 General Atomics Court, San Diego, CA 92121 (United States); Bensussan, Armand [INSERM U976, Hôpital Saint Louis, F-75475 Paris (France); Department of Immunology, Dermatology and Oncology, Univ Paris Diderot, Sorbonne Paris Cité, UMRS976 F-75475 Paris (France); Maricic, Igor; Kumar, Vipin [Torrey Pines Institute for Molecular Studies, Laboratory of Autoimmunity, 3550 General Atomics Court, San Diego, CA 92121 (United States); Braciak, Todd A., E-mail: tbraciak@tpims.org [Torrey Pines Institute for Molecular Studies, Division of Immune Regulation, 3550 General Atomics Court, San Diego, CA 92121 (United States)

    2011-07-13

    Vimentin was originally identified as an intermediate filament protein present only as an intracellular component in many cell types. However, this protein has now been detected on the surface of a number of different cancer cell types in a punctate distribution pattern. Increased vimentin expression has been indicated as an important step in epithelial-mesenchymal transition (EMT) required for the metastasis of prostate cancer. Here, using two vimentin-specific monoclonal antibodies (SC5 and V9 directed against the coil one rod domain and the C-terminus of the vimentin protein, respectively), we examined whether either of these domains would be displayed on the surface of three commonly studied prostate cancer cell lines isolated from different sites of metastases. Confocal analysis of LNCaP, PC3 and DU145 prostate cancer cell lines (derived from lymph node, bone or brain prostate metastases, respectively) demonstrated that both domains of vimentin are present on the surface of these metastatic cancer cell types. In addition, flow cytometric analysis revealed that vimentin expression was readily detected along with CD44 expression but only a small subpopulation of prostate cancer cells expressed vimentin and the putative stem cell marker CD133 along with CD44. Finally, Cowpea mosaic virus (CPMV) nanoparticles that target vimentin could bind and internalize into tested prostate cancer cell lines. These results demonstrate that at least two domains of vimentin are present on the surface of metastatic prostate cancer cells and suggest that vimentin could provide a useful target for nanoparticle- or antibody- cancer therapeutic agents directed against highly invasive cancer and/or stem cells.

  11. Enhanced enrichment of prostate cancer stem-like cells with miniaturized 3D culture in liquid core-hydrogel shell microcapsules

    Science.gov (United States)

    Yu, Jianhua; Lu, Xiongbin; Zynger, Debra L.; He, Xiaoming

    2015-01-01

    Cancer stem-like cells (CSCs) are rare subpopulations of cancer cells that are reported to be responsible for cancer resistance and metastasis associated with conventional cancer therapies. Therefore, effective enrichment/culture of CSCs is of importance to both the understanding and treatment of cancer. However, it usually takes approximately 10 days for the widely used conventional approach to enrich CSCs through the formation of CSC-containing aggregates. Here we report the time can be shortened to 2 days while obtaining prostate CSC-containing aggregates with better quality based on the expression of surface receptor markers, dye exclusion, gene and protein expression, and in vivo tumorigenicity. This is achieved by encapsulating and culturing human prostate cancer cells in the miniaturized 3D liquid core of microcapsules with an alginate hydrogel shell. The miniaturized 3D culture in core–shell microcapsules is an effective strategy for enriching/culturing CSCs in vitro to facilitate cancer research and therapy development. PMID:24952981

  12. Loss of let-7 up-regulates EZH2 in prostate cancer consistent with the acquisition of cancer stem cell signatures that are attenuated by BR-DIM.

    Directory of Open Access Journals (Sweden)

    Dejuan Kong

    Full Text Available The emergence of castrate-resistant prostate cancer (CRPC contributes to the high mortality of patients diagnosed with prostate cancer (PCa, which in part could be attributed to the existence and the emergence of cancer stem cells (CSCs. Recent studies have shown that deregulated expression of microRNAs (miRNAs contributes to the initiation and progression of PCa. Among several known miRNAs, let-7 family appears to play a key role in the recurrence and progression of PCa by regulating CSCs; however, the mechanism by which let-7 family contributes to PCa aggressiveness is unclear. Enhancer of Zeste homolog 2 (EZH2, a putative target of let-7 family, was demonstrated to control stem cell function. In this study, we found loss of let-7 family with corresponding over-expression of EZH2 in human PCa tissue specimens, especially in higher Gleason grade tumors. Overexpression of let-7 by transfection of let-7 precursors decreased EZH2 expression and repressed clonogenic ability and sphere-forming capacity of PCa cells, which was consistent with inhibition of EZH2 3'UTR luciferase activity. We also found that the treatment of PCa cells with BR-DIM (formulated DIM: 3,3'-diindolylmethane by Bio Response, Boulder, CO, abbreviated as BR-DIM up-regulated let-7 and down-regulated EZH2 expression, consistent with inhibition of self-renewal and clonogenic capacity. Moreover, BR-DIM intervention in our on-going phase II clinical trial in patients prior to radical prostatectomy showed upregulation of let-7 consistent with down-regulation of EZH2 expression in PCa tissue specimens after BR-DIM intervention. These results suggest that the loss of let-7 mediated increased expression of EZH2 contributes to PCa aggressiveness, which could be attenuated by BR-DIM treatment, and thus BR-DIM is likely to have clinical impact.

  13. Targeting Quiescence in Prostate Cancer

    Science.gov (United States)

    2016-10-01

    cell quiescence, cancer recurrence 16. SECURITY CLASSIFICATION OF: 17...limit to 20 words). GAS6 Growth arrest specific 6 HSC Hematopoietic stem cells HSC Niche Hematopoietic Stem Cell Niche PC3 Prostate...distributions of cancer cells in the Hematopoietic Stem cell niche* (Timepoints throughout 1-7 months will be examined) 1-7 months Optimization

  14. Prostate Ultrasound

    Medline Plus

    Full Text Available ... Prostatic Hyperplasia (BPH) (Enlargement of the Prostate) Prostate ... physician. To locate a medical imaging or radiation oncology provider in your community, you can search the ...

  15. Double-negative feedback loop between ZEB2 and miR-145 regulates epithelial-mesenchymal transition and stem cell properties in prostate cancer cells.

    Science.gov (United States)

    Ren, Dong; Wang, Min; Guo, Wei; Huang, Shuai; Wang, Zeyu; Zhao, Xiaohui; Du, Hong; Song, Libing; Peng, Xinsheng

    2014-12-01

    The invasion and metastasis of tumors are triggered by an epithelial to mesenchymal transition (EMT), which is regulated by microRNAs (miRNAs). EMT also promotes malignant tumor progression and the maintenance of the stem cell property, which endows cancer cells with the capabilities of self-renewal and immortalized proliferation. The transcriptional repressor zinc-finger E-box binding homeobox 2 (ZEB2), as an EMT activator, might be an important promoter of metastasis in some tumors. Here, we report that ZEB2 directly represses the transcription of miR-145, which is a strong repressor of EMT. In turn, ZEB2 is also a direct target of miR-145. Further, our findings show that the downregulation of ZEB2 not only represses invasion, migration, EMT, and the stemness of prostate cancer (PCa) cells, but also suppresses the capability of PC-3 cells to invade bone in vivo. Importantly, the expression level of ZEB2 as revealed by immunohistochemical analysis is positively correlated to bone metastasis, the serum free PSA level, the total PSA level, and the Gleason score in PCa patients and is negatively correlated with miR-145 expression in primary PCa specimens. Thus, our findings demonstrate a double-negative feedback loop between ZEB2 and miR-145 and indicate that the ZEB2/miR-145 double-negative feedback loop plays a significant role in the control of EMT and stem cell properties during the bone metastasis of PCa cells. These results suggest that the double-negative feedback loop between ZEB2 and miR-145 contributes to PCa progression and metastasis and might have therapeutic relevance for the bone metastasis of PCa.

  16. Effect of PUFAs from Pteleopsis suberosa stem bark on androgenic enzymes, cellular ATP and prostatic acid phosphatase in mercury chloride – Exposed rat

    Directory of Open Access Journals (Sweden)

    J.K. Akintunde

    2017-09-01

    Full Text Available Occupational and environmental exposure to mercury causes varieties of adverse reproductive disorders in mammals. The present study was designed to investigate the unsaturated fatty acids of Pteleopsis suberosa stem bark extract (PTSSBE, evaluate its antioxidant properties and examine its biochemical targets on sub-acute mercury-induced testicular dysfunctions. Rats were divided into five groups of 10 animals each. Group I was given distilled water; group II, III, IV and V was orally administered with mercury at a dose of 3.75 mg/kg body weight. Group III, IV and V were co-treated with PTSSBE of 25, 50 and 100 mg/kg body weight respectively, for 10 days. Rats exposed to mercury significantly decreased the activities of catalase (CAT, lactate dehydrogenase (LDH, and the level of reduced glutathione (GSH, while the formation of malondialdehyde (MDA was increased. There was also a marked significant decrease (p < 0.05 in testicular activities of Δ5-3β-hydroxysteroid dehydrogenase and Δ5 17β-hydroxysteroid dehydrogenase. Moreover, the activities of prostatic acid phosphatase, total acid phosphatase and prostatic alkaline phosphatase, were significantly (p < 0.05 elevated in mercury treated rats. These effects were prevented by co-treatment with PTSSBE in mercury-induced testicular toxicity in rats. Aphrosidiac effects of Pteleopsis suberosa, may find clinical application in reproductive abnormalities. Isolation and translation of individual active ingredient would help to find new drugs to cure and/or prevent male infertility among mercury exposed workers.

  17. Prostate Ultrasound

    Medline Plus

    Full Text Available ... News Physician Resources Professions Site Index A-Z Ultrasound - Prostate Ultrasound of the prostate uses sound waves ... the limitations of Prostate Ultrasound Imaging? What is Ultrasound Imaging of the Prostate? Ultrasound is safe and ...

  18. Prostate Ultrasound

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    Full Text Available ... as detailed as with the transrectal probe. An MRI of the pelvis may be obtained as an ... Enlargement of the Prostate) Prostate Cancer Ultrasound- and MRI-Guided Prostate Biopsy Images related to Ultrasound - Prostate ...

  19. Pathobiological implications of the expression of EGFR, pAkt, NF-κB and MIC-1 in prostate cancer stem cells and their progenies.

    Directory of Open Access Journals (Sweden)

    Murielle Mimeault

    Full Text Available The progression of prostate cancers (PCs to locally invasive, androgen-independent and metastatic disease states is generally associated with treatment resistance and disease relapse. The present study was undertaken to establish the possibility of using a combination of specific oncogenic products, including epidermal growth factor receptor (EGFR, pAkt, nuclear factor-kappaB (NF-κB and macrophage inhibitory cytokine-1 (MIC-1 as biomarkers and therapeutic targets for optimizing the management of patients with localized PC at earlier disease stages. The immunohistochemical and immunofluorescence data have revealed that the expression levels of EGFR, Ser(473-pAkt, NF-κB p65 and MIC-1 proteins were significantly enhanced in the same subset of 76 cases of prostatic adenocarcinoma specimens during the disease progression and these biomarkers were expressed in a small subpopulation of CD133(+ PC cells and the bulk tumor mass of CD133(- PC cells. Importantly, all of these biomarkers were also overexpressed in 80-100% of 30 PC metastasis bone tissue specimens. Moreover, the results have indicated that the EGF-EGFR signaling pathway can provide critical functions for the self-renewal of side population (SP cells endowed with stem cell-like features from highly invasive WPE1-NB26 cells. Of therapeutic interest, the targeting of EGFR, pAkt, NF-κB or MIC-1 was also effective at suppressing the basal and EGF-promoted prostasphere formation by SP WPE1-NB26 cells, inducing disintegration of SP cell-derived prostaspheres and decreasing the viability of SP and non-SP WPE1-NB26 cell fractions. Also, the targeting of these oncogenic products induced the caspase-dependent apoptosis in chemoresistant SP WPE1-NB26 cells and enhanced their sensibility to the cytotoxic effects induced by docetaxel. These findings suggest that the combined use of EGFR, pAkt, NF-κB and/or MIC-1 may represent promising strategies for improving the accuracy of current diagnostic and

  20. The Prostate

    Science.gov (United States)

    ... Publications Reports What You Need To Know About™ Prostate Cancer This booklet is about prostate cancer. Learning about medical care for your cancer ... ePub This booklet covers: The anatomy of the prostate and basics about prostate cancer Treatments for prostate ...

  1. Prostate Ultrasound

    Medline Plus

    Full Text Available ... Physician Resources Professions Site Index A-Z Ultrasound - Prostate Ultrasound of the prostate uses sound waves to ... Ultrasound Imaging? What is Ultrasound Imaging of the Prostate? Ultrasound is safe and painless, and produces pictures ...

  2. Prostate brachytherapy

    Science.gov (United States)

    Implant therapy - prostate cancer; Radioactive seed placement; Internal radiation therapy - prostate; High dose radiation (HDR) ... place the seeds that deliver radiation into your prostate. The seeds are placed with needles or special ...

  3. Prostate Ultrasound

    Medline Plus

    Full Text Available ... Z Ultrasound - Prostate Ultrasound of the prostate uses sound waves to produce pictures of a man’s prostate ... pictures of the inside of the body using sound waves. Ultrasound imaging, also called ultrasound scanning or ...

  4. Prostate Ultrasound

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    Full Text Available ... of the prostate uses sound waves to produce pictures of a man’s prostate gland and to help ... Prostate? Ultrasound is safe and painless, and produces pictures of the inside of the body using sound ...

  5. Prostate Ultrasound

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    Full Text Available ... Ultrasound - Prostate Ultrasound of the prostate uses sound waves to produce pictures of a man’s prostate gland ... of the inside of the body using sound waves. Ultrasound imaging, also called ultrasound scanning or sonography , ...

  6. Prostate Ultrasound

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    Full Text Available ... Prostate Ultrasound Imaging? What is Ultrasound Imaging of the Prostate? Ultrasound is safe and painless, and produces ... of page What are some common uses of the procedure? A transrectal ultrasound of the prostate gland ...

  7. Prostate Ultrasound

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    Full Text Available ... prostate. help diagnose the cause of a man's infertility. A transrectal ultrasound of the prostate gland is ... of page How is the procedure performed? In men, the prostate gland is located directly in front ...

  8. Enrichment of the Cancer Stem Phenotype in Sphere Cultures of Prostate Cancer Cell Lines Occurs through Activation of Developmental Pathways Mediated by the Transcriptional Regulator ΔNp63α.

    Directory of Open Access Journals (Sweden)

    Roberto Portillo-Lara

    Full Text Available Cancer stem cells (CSC drive prostate cancer tumor survival and metastasis. Nevertheless, the development of specific therapies against CSCs is hindered by the scarcity of these cells in prostate tissues. Suspension culture systems have been reported to enrich CSCs in primary cultures and cell lines. However, the molecular mechanisms underlying this phenomenon have not been fully explored.We describe a prostasphere assay for the enrichment of CD133+ CSCs in four commercial PCa cell lines: 22Rv1, DU145, LNCaP, and PC3. Overexpression of CD133, as determined by flow cytometric analysis, correlated with an increased clonogenic, chemoresistant, and invasive potential in vitro. This phenotype is concordant to that of CSCs in vivo. Gene expression profiling was then carried out using the Cancer Reference panel and the nCounter system from NanoString Technologies. This analysis revealed several upregulated transcripts that can be further explored as potential diagnostic markers or therapeutic targets. Furthermore, functional annotation analysis suggests that ΔNp63α modulates the activation of developmental pathways responsible for the increased stem identity of cells growing in suspension cultures.We conclude that profiling the genetic mechanisms involved in CSC enrichment will help us to better understand the molecular pathways that underlie CSC pathophysiology. This platform can be readily adapted to enrich and assay actual patient samples, in order to design patient-specific therapies that are aimed particularly against CSCs.

  9. Prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, G.P.; Kuss, R., Khoury, S.; Chatelain, C.; Denis, L.

    1987-01-01

    This book contains over 70 selections. Some of the titles are: Place of the Computed Tomography in the Staging of Prostatic Cancer; Magnetic Resonance Imaging (MRI) in Staging of the Prostatic Cancer; Magnetic Resonance Imaging of the Prostate; Long-Term Results in Radiotherapy of Prostatic Cancer; Interstitial Irradiation Using I-125 Seeds; and Treatment of Cancer of the Prostate by Use of Physiotherapy: Long-Term Results.

  10. Prostate Ultrasound

    Medline Plus

    Full Text Available ... with measurements acquired as needed for any treatment planning. detect an abnormal growth within the prostate. help ... ultrasound , there are no known harmful effects on humans. top of ... Radiation Therapy for Prostate Cancer top ...

  11. Prostate Ultrasound

    Medline Plus

    Full Text Available ... nodule felt by a physician during a routine physical exam or prostate cancer screening exam. an elevated ... page Additional Information and Resources RTAnswers.org Radiation Therapy for Prostate Cancer top of page This page ...

  12. Prostate Ultrasound

    Medline Plus

    Full Text Available ... a physician during a routine physical exam or prostate cancer screening exam. an elevated blood test result. difficulty ... Information and Resources RTAnswers.org Radiation Therapy for Prostate Cancer top of page This page was reviewed on ...

  13. Prostate Ultrasound

    Medline Plus

    Full Text Available ... What are the limitations of Prostate Ultrasound Imaging? What is Ultrasound Imaging of the Prostate? Ultrasound is safe and painless, and produces pictures of the inside of the body using ...

  14. Prostate Cancer

    Science.gov (United States)

    ... man's bladder that produces fluid for semen. Prostate cancer is common among older men. It is rare ... younger than 40. Risk factors for developing prostate cancer include being over 65 years of age, family ...

  15. Prostate Ultrasound

    Medline Plus

    Full Text Available ... uses sound waves to produce pictures of a man’s prostate gland and to help diagnose symptoms such ... also called transrectal ultrasound, provides images of a man's prostate gland and surrounding tissue. The exam typically ...

  16. Prostate Ultrasound

    Medline Plus

    Full Text Available ... the prostate gland which is situated right in front of the rectum. top of page What are ... men, the prostate gland is located directly in front of the rectum, so the ultrasound exam is ...

  17. Prostate Ultrasound

    Medline Plus

    Full Text Available ... What are the limitations of Prostate Ultrasound Imaging? What is Ultrasound Imaging of the Prostate? Ultrasound is ... in front of the rectum. top of page What are some common uses of the procedure? A ...

  18. Prostate Ultrasound

    Medline Plus

    Full Text Available ... BPH) , with measurements acquired as needed for any treatment planning. detect an abnormal growth within the prostate. help diagnose the cause of a man's infertility. A transrectal ultrasound of the prostate gland is ...

  19. Prostate Ultrasound

    Medline Plus

    Full Text Available ... about radiology? Share your patient story here Images × Image Gallery Radiologist and patient consultation. View full size with caption Related Articles and Media Benign Prostatic Hyperplasia (BPH) (Enlargement of the Prostate) ...

  20. Prostate biopsy

    Science.gov (United States)

    ... from the prostate through the scope. Perineal - through perineum (the skin between the anus and the scrotum). ... pain. A small cut is made in the perineum. A needle is inserted to collect prostate tissue. ...

  1. Prostate Ultrasound

    Medline Plus

    Full Text Available ... of page How is the procedure performed? In men, the prostate gland is located directly in front ... What are the limitations of Prostate Ultrasound Imaging? Men who have had the tail end of their ...

  2. Prostate Ultrasound

    Medline Plus

    Full Text Available Toggle navigation Test/Treatment Patient Type Screening/Wellness Disease/Condition Safety En Español More Info Images/Videos ... of the prostate gland is performed to: detect disorders within the prostate. determine whether the prostate is ...

  3. Prostate Ultrasound

    Medline Plus

    Full Text Available ... blood, may be administered to determine if a patient is at high risk for cancer. In this case, a biopsy is performed and ... patient story here Images × Image Gallery ... Hyperplasia (BPH) (Enlargement of the Prostate) Prostate Cancer Ultrasound- and MRI-Guided Prostate Biopsy Images related ...

  4. Prostate Diseases

    Science.gov (United States)

    The prostate is a gland in men. It helps make semen, the fluid that contains sperm. The prostate surrounds the tube that carries urine away from ... and out of the body. A young man's prostate is about the size of a walnut. It ...

  5. Prostate Ultrasound

    Medline Plus

    Full Text Available ... are the limitations of Prostate Ultrasound Imaging? What is Ultrasound Imaging of the Prostate? Ultrasound is safe and painless, and produces ... top of page What are some common uses of the procedure? A transrectal ultrasound of the prostate ...

  6. Advanced Prostate Cancer

    Science.gov (United States)

    ... castrate-resistant prostate cancer or CRPC) Metastatic prostate cancer Prostate cancer is metastatic if it has spread to: • ... first diagnosis, but it does happen. Castrate-resistant prostate cancer (CRPC) Castrate-resistant prostate cancer (CRPC) is when ...

  7. Prostate Cancer Prevention

    Science.gov (United States)

    ... Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer All ... Cancer Treatment Prostate Cancer Prevention Genetics of Prostate Cancer Prostate Cancer Screening Research Prostate Cancer Prevention (PDQ®)–Patient ...

  8. Stages of Prostate Cancer

    Science.gov (United States)

    ... Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer All ... Cancer Treatment Prostate Cancer Prevention Genetics of Prostate Cancer Prostate Cancer Screening Research Prostate Cancer Treatment (PDQ®)–Patient ...

  9. Prostate Ultrasound

    Medline Plus

    Full Text Available ... through blood vessels. Ultrasound imaging is a noninvasive medical test that helps physicians diagnose and treat medical conditions. Prostate ultrasound, also called transrectal ultrasound, provides ...

  10. Prostate Ultrasound

    Medline Plus

    Full Text Available ... BPH) , with measurements acquired as needed for any treatment planning. detect an abnormal growth within the prostate. help diagnose the cause of a man's infertility. A transrectal ultrasound of the prostate gland is typically used to help diagnose symptoms such as: a nodule felt by a physician ...

  11. Chronic prostatitis.

    Science.gov (United States)

    Batstone, G Richard D; Doble, Andrew; Batstone, D

    2003-01-01

    This review covers recent developments in the classification, epidemiology, aetiology, diagnosis and treatment of patients diagnosed with chronic prostatitis (NIH classification types II, IIIa/IIIb and IV prostatitis) in the period of review (2001-2002). Recent studies highlight some of the problems with the 1995 NIH classification. Epidemiological studies have confirmed that "prostatitis" is common, with a prevalence of 10-15%. Associations of prostatitis include benign prostatic hyperplasia, sexually transmitted disease, lower urinary tract symptoms, stress, and reduced sunlight exposure. Elevated levels of cytokines in the seminal plasma and prostatic secretions have been detected in men with chronic prostatitis compared with normal individuals, suggesting an active inflammatory process in the male genital tract. This inflammatory reaction may be mediated by an adaptive immune response directed against a genital tract antigen(s) (autoimmunity). Increased levels of bacterial 16S ribosomal DNA in the prostates of men with chronic prostatitis compared with controls are compatible with the notion that a bacterial inflammatory event initiates an auto-immune process; however, the role of bacteria in the continuation of symptoms is unknown. The aetiology of chronic pelvic pain syndrome is still not certain, although an auto-immune process is favoured. Further research is required to determine the putative auto-antigen, the immune responses of patients, the role of bacteria in the inflammatory process, and the patients' pain response to genitourinary insults. As yet no diagnostic tests (other than to eliminate other pathology) and few treatments for chronic prostatitis can be recommended on the basis of scientific evidence.

  12. MRI of the Prostate

    Science.gov (United States)

    ... News Physician Resources Professions Site Index A-Z Magnetic Resonance Imaging (MRI) - Prostate Magnetic resonance imaging (MRI) of the prostate ... limitations of MRI of the Prostate? What is MRI of the Prostate? Magnetic resonance imaging (MRI) is ...

  13. Cryotherapy for prostate cancer

    Science.gov (United States)

    Cryosurgery-prostate cancer; Cryoablation-prostate cancer ... Prostate Cancer. American Cancer Society. www.cancer.org/cancer/prostatecancer/detailedguide/prostate-cancer-treating-cryosurgery. Accessed August 31, 2015. Horwich ...

  14. Screening for Prostate Cancer

    Science.gov (United States)

    ... it might mean for you. What is prostate cancer? Prostate cancer is a cancer that occurs in the ... in front of the rectum. Screening for Prostate Cancer Prostate cancer is the second most common cancer in ...

  15. Prostate Cancer FAQs

    Science.gov (United States)

    ... procedures with your doctor. How common is prostate cancer? Prostate cancer is the most common non-skin cancer ... prostate cancer detected? What are the symptoms of prostate cancer? If the cancer is caught at its earliest ...

  16. Prostate Cancer (Radiation Therapy)

    Science.gov (United States)

    ... Physician Resources Professions Site Index A-Z Prostate Cancer Treatment Prostate cancer overview? What are my treatment options? What ... any new developments in treating my disease? Prostate cancer overview Prostate cancer is the most common form of cancer ...

  17. Benign prostate hyperplasia (BPH) - resources

    Science.gov (United States)

    Resources - benign prostatic hyperplasia (BPH); Prostate enlargement resources; BPH resources ... following organizations provide information on benign prostatic hyperplasia ( prostate enlargement ): National Kidney and Urologic Diseases Information Clearinghouse -- ...

  18. Xanthogranulomatous Prostatitis, a Rare Prostatic Entity

    Directory of Open Access Journals (Sweden)

    Alejandro Noyola

    2017-01-01

    Full Text Available There are several benign prostatic pathologies that can clinically mimic a prostate adenocarcinoma. Xanthogranulomatous prostatitis is a benign inflammatory condition of the prostate and a rare entity. A 47-year old male, with 3 years of lower urinary tract symptoms, with a palpable hypogastric tumor, digital rectal examination: solid prostate, of approximately 60 g. Initial PSA was 0.90 ng/mL. He underwent surgical excision of the lower abdominal nodule and prostatectomy. Histopathology showed xanthogranulomatous prostatitis, without malignancy. Xanthogranulomatous prostatitis is an extremely rare entity that can simulate prostate adenocarcinoma, therefore having a correct histopathological diagnosis is essential.

  19. Prostate Ultrasound

    Medline Plus

    Full Text Available ... abnormal growth within the prostate. help diagnose the cause of a man's infertility. A transrectal ultrasound of ... show up well on x-ray images. Ultrasound causes no health problems and may be repeated as ...

  20. Prostate Ultrasound

    Medline Plus

    Full Text Available ... receiver coil. top of page Additional Information and Resources RTAnswers.org Radiation Therapy for Prostate Cancer top ... here Images × Image Gallery Radiologist and patient consultation. View full size with caption Related Articles and Media ...

  1. Prostate Ultrasound

    Medline Plus

    Full Text Available ... abnormal area in the prostate gland for later laboratory testing. top of page How should I prepare? ... by Please note RadiologyInfo.org is not a medical facility. Please contact your physician with specific medical ...

  2. Prostate Ultrasound

    Medline Plus

    Full Text Available ... physician during a routine physical exam or prostate cancer screening exam. an elevated blood test result. difficulty ... if a patient is at high risk for cancer. In this case, a biopsy is performed and ...

  3. Prostate Ultrasound

    Medline Plus

    Full Text Available ... less than 20 minutes. top of page What will I experience during and after the procedure? Ultrasound ... in the region of the prostate. A biopsy will add time to the procedure. Rarely, a small ...

  4. Prostate Ultrasound

    Medline Plus

    Full Text Available ... safe, noninvasive, and does not use ionizing radiation. This procedure requires little to no special preparation. Leave ... examination, an ultrasound-guided biopsy can be performed. This procedure involves advancing a needle into the prostate ...

  5. Prostate Ultrasound

    Medline Plus

    Full Text Available ... physician during a routine physical exam or prostate cancer screening exam. an elevated blood test result. difficulty urinating. Because ultrasound provides real-time images, it also can be used to guide ...

  6. Prostatitis - nonbacterial

    Science.gov (United States)

    ... urinary tract Parasites Pelvic floor muscle problem Sexual abuse Viruses Life stresses and emotional factors may play ... to treat the condition. These include: Long-term antibiotics to make sure that the prostatitis is not ...

  7. Prostate Ultrasound

    Medline Plus

    Full Text Available ... abnormal area in the prostate gland for later laboratory testing. top of page How should I prepare? ... object is solid or filled with fluid). In medicine, ultrasound is used to detect changes in appearance, ...

  8. Prostate Ultrasound

    Medline Plus

    Full Text Available ... used to sample cells (tissue) from an abnormal area in the prostate gland for later laboratory testing. ... to remove all clothing and jewelry in the area to be examined. You may be asked to ...

  9. Prostate Ultrasound

    Medline Plus

    Full Text Available ... a nodule felt by a physician during a routine physical exam or prostate cancer screening exam. an ... you should be able to resume your normal activities immediately. top of page Who interprets the results ...

  10. Prostate Ultrasound

    Medline Plus

    Full Text Available ... phased array) receiver coil. top of page Additional Information and Resources RTAnswers.org Radiation Therapy for Prostate ... Send us your feedback Did you find the information you were looking for? Yes No Please type ...

  11. Prostate Ultrasound

    Medline Plus

    Full Text Available ... The image is created based on the amplitude (loudness), frequency (pitch) and time it takes for the ... for Prostate Cancer top of page This page was reviewed on March 17, 2016 Send us your ...

  12. Prostate Ultrasound

    Medline Plus

    Full Text Available ... to investigate a nodule found during a rectal exam, detect abnormalities, and determine whether the gland is ... a man's prostate gland and surrounding tissue. The exam typically requires insertion of an ultrasound probe into ...

  13. Prostate Ultrasound

    Medline Plus

    Full Text Available ... biopsy is planned, you may be told to avoid aspirin and other blood thinners for seven to ... abnormal growth within the prostate. help diagnose the cause of a man's infertility. A transrectal ultrasound of ...

  14. Prostate Ultrasound

    Medline Plus

    Full Text Available ... nodule felt by a physician during a routine physical exam or prostate cancer screening exam. an elevated ... requested the exam. Usually, the referring physician or health care provider will share the results with you. ...

  15. Prostate Ultrasound

    Medline Plus

    Full Text Available ... rectum into the prostate gland which is situated right in front of the rectum. top of page ... at these links. About Us | Contact Us | FAQ | Privacy | Terms of Use | Links | Site Map Copyright © 2017 ...

  16. Prostate Ultrasound

    Medline Plus

    Full Text Available ... information you were looking for? Yes No Please type your comment or suggestion into the following text box: Comment: ... Images related to Ultrasound - Prostate Sponsored by Please ...

  17. Prostate Ultrasound

    Medline Plus

    Full Text Available ... needed for any treatment planning. detect an abnormal growth within the prostate. help diagnose the cause of ... requested the exam. Usually, the referring physician or health care provider will share the results with you. ...

  18. Prostate Ultrasound

    Medline Plus

    Full Text Available ... physician during a routine physical exam or prostate cancer screening exam. an elevated blood test result. difficulty ... vessels or to detect abnormal masses, such as tumors. In an ultrasound examination, a transducer both sends ...

  19. Prostate Ultrasound

    Medline Plus

    Full Text Available ... prostate gland while the radiologist watches the needle placement with ultrasound. A small amount of tissue is ... on x-ray images. Ultrasound causes no health problems and may be repeated as often as is ...

  20. Prostate Ultrasound

    Medline Plus

    Full Text Available ... are obtained from different angles to get the best view of the prostate gland. If a suspicious ... over time. Follow-up examinations are sometimes the best way to see if treatment is working or ...

  1. Prostate Cancer

    Science.gov (United States)

    ... semen Discomfort in the pelvic area Bone pain Erectile dysfunction When to see a doctor Make an appointment ... Treatment options may include medications, catheters and surgery. Erectile dysfunction. Erectile dysfunction can result from prostate cancer or ...

  2. Prostate Ultrasound

    Medline Plus

    Full Text Available ... be necessary. Your doctor will explain the exact reason why another exam is requested. Sometimes a follow- ... and Resources RTAnswers.org Radiation Therapy for Prostate Cancer top of page This page was reviewed on ...

  3. Prostate Ultrasound

    Medline Plus

    Full Text Available ... Ultrasound provides real-time imaging, making it a good tool for guiding minimally invasive procedures such as ... bowel (rectum) removed during prior surgery are not good candidates for ultrasound of the prostate gland because ...

  4. STEM, STEM Education, STEMmania

    Science.gov (United States)

    Sanders, Mark

    2009-01-01

    In this article, the author introduces integrative STEM (science, technology, engineering, and/or mathematics) education and discusses the importance of the program. The notion of integrative STEM education includes approaches that explore teaching and learning between/among any two or more of the STEM subject areas, and/or between a STEM subject…

  5. Prostate cancer

    DEFF Research Database (Denmark)

    Chabanova, Elizaveta; Balslev, Ingegerd; Logager, Vibeke

    2011-01-01

    To investigate diagnostic accuracy of detection of prostate cancer by magnetic resonance: to evaluate the performance of T2WI, DCEMRI and CSI and to correlate the results with biopsy and radical prostatectomy histopathological data.......To investigate diagnostic accuracy of detection of prostate cancer by magnetic resonance: to evaluate the performance of T2WI, DCEMRI and CSI and to correlate the results with biopsy and radical prostatectomy histopathological data....

  6. Prostatitis: Inflammation of the Prostate

    Science.gov (United States)

    ... symptoms before diagnosing prostatitis. Personal and Family Medical History Taking a personal and family medical history is ... anti-inflammatory drugs—also called NSAIDs—such as aspirin, ibuprofen, and naproxen sodium glycosaminogly cans such as ...

  7. CXCR4 expression in prostate cancer progenitor cells.

    Directory of Open Access Journals (Sweden)

    Anna Dubrovska

    Full Text Available Tumor progenitor cells represent a population of drug-resistant cells that can survive conventional chemotherapy and lead to tumor relapse. However, little is known of the role of tumor progenitors in prostate cancer metastasis. The studies reported herein show that the CXCR4/CXCL12 axis, a key regulator of tumor dissemination, plays a role in the maintenance of prostate cancer stem-like cells. The CXCL4/CXCR12 pathway is activated in the CD44(+/CD133(+ prostate progenitor population and affects differentiation potential, cell adhesion, clonal growth and tumorigenicity. Furthermore, prostate tumor xenograft studies in mice showed that a combination of the CXCR4 receptor antagonist AMD3100, which targets prostate cancer stem-like cells, and the conventional chemotherapeutic drug Taxotere, which targets the bulk tumor, is significantly more effective in eradicating tumors as compared to monotherapy.

  8. Stem Cells

    Science.gov (United States)

    Stem cells are cells with the potential to develop into many different types of cells in the body. ... the body. There are two main types of stem cells: embryonic stem cells and adult stem cells. Stem ...

  9. Epithelial-mesenchymal transition in prostate cancer: an overview

    Science.gov (United States)

    Montanari, Micaela; Rossetti, Sabrina; Cavaliere, Carla; D'Aniello, Carmine; Malzone, Maria Gabriella; Vanacore, Daniela; Franco, Rossella Di; Mantia, Elvira La; Iovane, Gelsomina; Piscitelli, Raffaele; Muscariello, Raffaele; Berretta, Massimiliano; Perdonà, Sisto; Muto, Paolo; Botti, Gerardo; Bianchi, Attilio Antonio Montano; Veneziani, Bianca Maria; Facchini, Gaetano

    2017-01-01

    Prostate cancer is a main urological disease associated with significant morbidity and mortality. Radical prostatectomy and radiotherapy are potentially curative for localized prostate cancer, while androgen deprivation therapy is the initial systemic therapy for metastatic prostate disease. However, despite temporary response, most patients relapse and evolve into castration resistant cancer. Epithelial-mesenchymal transition (EMT) is a complex gradual process that occurs during embryonic development and/or tumor progression. During this process, cells lose their epithelial characteristics and acquire mesenchymal features. Increasing evidences indicate that EMT promotes prostate cancer metastatic progression and it is closely correlated with increased stemness and drug resistance. In this review, we discuss the main molecular events that directly or indirectly govern the EMT program in prostate cancer, in order to better define the role and the mechanisms underlying this process in prostate cancer progression and therapeutic resistance. PMID:28430640

  10. A phase 2 study of high-activity {sup 186}Re-HEDP with autologous peripheral blood stem cell transplant in progressive hormone-refractory prostate cancer metastatic to bone

    Energy Technology Data Exchange (ETDEWEB)

    O' Sullivan, J.M. [Queen' s University Belfast/Belfast City Hospital, Department of Oncology, Belfast (United Kingdom); Norman, A.R. [Royal Marsden Foundation NHS Trust, Department of Computing, Sutton, Surrey (United Kingdom); McCready, V.R.; Flux, G.; Buffa, F.M. [Royal Marsden Foundation NHS Trust, Department of Physics, Sutton, Surrey (United Kingdom); Johnson, B. [Royal Marsden Foundation NHS Trust, Bob Champion Unit, Sutton, Surrey (United Kingdom); Coffey, J.; Horwich, A.; Huddart, R.A.; Parker, C.C.; Dearnaley, D.P. [Royal Marsden Foundation NHS Trust, Academic Unit of Urology, Sutton, Surrey (United Kingdom); Cook, G. [Royal Marsden Foundation NHS Trust, Department of Nuclear Medicine, Sutton, Surrey (United Kingdom); Treleaven, J. [Royal Marsden Foundation NHS Trust, Department of Haematology, Sutton, Surrey (United Kingdom)

    2006-09-15

    We investigated the potential for improvement in disease control by use of autologous peripheral blood stem cell transplant (PBSCT) to permit administration of high activities of {sup 186}Re-hydroxyethylidene diphosphonate (HEDP) in patients with progressive hormone-refractory prostate cancer (HRPC). Eligible patients had progressive HRPC metastatic to bone, good performance status and minimal soft tissue disease. Patients received 5,000 MBq of {sup 186}Re-HEDP i.v., followed 14 days later by PBSCT. Response was assessed using PSA, survival, pain scores and quality of life. Thirty-eight patients with a median age of 67 years (range 50-77) and a median PSA of 57 ng/ml (range 4-3,628) received a median activity of 4,978 MBq {sup 186}Re-HEDP (range 4,770-5,100 MBq). The most serious toxicity was short-lived grade 3 thrombocytopenia in 8 (21%) patients. The median survival of the group is 21 months (95%CI 18-24 months) with Kaplan-Meier estimated 1- and 2-year survival rates of 83% and 40% respectively. Thirty-one patients (81%, 95% CI 66-90%) had stable or reduced PSA levels 3 months post therapy while 11 (29%, 95% CI 15-49%) had PSA reductions of >50% lasting >4 weeks. Quality of life measures were stable or improved in 27 (66%) at 3 months. We have shown that it is feasible and safe to deliver high-activity radioisotope therapy with PBSCT to men with metastatic HRPC. Response rates and survival data are encouraging; however, further research is needed to define optimal role of this treatment approach. (orig.)

  11. Prostatic leiomyosarcoma.

    Science.gov (United States)

    Csata, S; Orosz, Z; Iványi, A; Répássy, D

    1998-02-15

    The histopathological findings from the third prostate operation of a 63-year-old patient proved that his leiomysarcoma was malignant. Leiomyosarcoma is a disease of low incidence. Of 1000 cases of a carcinoma of prostate one proves to be this disease. Its clinical distinction from benign prostate disease meets difficulties. A survey of literature has shown that even multiple aggressive therapy fails when the process has overpassed the limits of the organ. Early diagnosis followed be radical pre- and postoperative X-irradiation may lead to long-term survival. Neither cytostatic nor hormonal therapy is successful. The course of the illness of our patients merits interest because of the rarity of the disease and the diagnostic difficulties.

  12. STEM, STEM Education, STEMmania

    OpenAIRE

    Sanders, Mark E.

    2008-01-01

    A series of circumstances has once more created an opportunity for technology educators to develop and implement new integrative approaches to STEM education championed by STEM education reform doctrine over the past two decades.

  13. Prostate Cancer Symptoms

    Science.gov (United States)

    ... Fundraise for PCF: Many vs Cancer Contact Us Prostate Cancer Symptoms and Signs Prostate Cancer Basics About the ... earlier. So what are the warning signs of prostate cancer? Unfortunately, there usually aren’t any early warning ...

  14. Prostate cancer - treatment

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000403.htm Prostate cancer - treatment To use the sharing features on this ... a combination of drugs is recommended. References National Cancer Institute. Prostate cancer treatment (PDQ): Stages of prostate cancer. Updated ...

  15. Prostate Cancer Symptoms

    Science.gov (United States)

    ... Fundraise for PCF: Many vs Cancer Contact Us Prostate Cancer Symptoms and Signs Prostate Cancer Basics About ... earlier. So what are the warning signs of prostate cancer? Unfortunately, there usually aren’t any early ...

  16. Prostate Cancer Foundation News

    Science.gov (United States)

    ... when men who are being treated with androgen deprivation therapy (ADT) see their PSA levels begin to... ... fight against prostate cancer today. Donate Terms of use Privacy Policy © Prostate Cancer Foundation, 2018 Understanding Prostate ...

  17. Prostate Ultrasound

    Medline Plus

    Full Text Available ... cells (tissue) from an abnormal area in the prostate gland for later laboratory testing. top of page How should I prepare? You should wear comfortable, loose-fitting clothing for your ultrasound exam. You may need to remove all clothing and jewelry in the area to be ...

  18. Prostatitis - acute

    Science.gov (United States)

    ... prostatitis at home : Urinate often and completely. Take warm baths to relieve pain. Take stool softeners to make bowel movements more comfortable. Avoid substances that irritate your bladder, such as alcohol, caffeinated foods and drinks, citrus juices, and hot or spicy foods. Drink more fluid (64 to ...

  19. Prostate Ultrasound

    Medline Plus

    Full Text Available ... transducer sends out high-frequency sound waves (that the human ear cannot hear) into the body and then ... ultrasound , there are no known harmful effects on humans. top of page What are the limitations of Prostate Ultrasound Imaging? Men who have ...

  20. Prostate Ultrasound

    Medline Plus

    Full Text Available ... as needle biopsies and fluid aspiration. Risks For standard diagnostic ultrasound , there are no known harmful effects on humans. top of page What are the limitations of Prostate Ultrasound Imaging? Men who have had the tail end of their bowel ( ...

  1. Prostate Ultrasound

    Medline Plus

    Full Text Available Toggle navigation Test/Treatment Patient Type Screening/Wellness Disease/Condition Safety En Español More Info Images/Videos About Us News Physician Resources Professions Site Index A-Z Ultrasound - Prostate Ultrasound of ...

  2. Prostate Ultrasound

    Medline Plus

    Full Text Available ... of the pelvis may be obtained as an alternative imaging test, because it may be obtained with an external (phased array) receiver coil. top of page Additional Information and Resources RTAnswers.org Radiation Therapy for Prostate Cancer top of page This page was reviewed on ...

  3. Prostate Ultrasound

    Medline Plus

    Full Text Available ... symptoms such as difficulty urinating or an elevated blood test result. It’s also used to investigate a nodule ... exam or prostate cancer screening exam. an elevated blood test result. difficulty urinating. Because ultrasound provides real-time ...

  4. Prostate brachytherapy - discharge

    Science.gov (United States)

    Implant therapy - prostate cancer - discharge; Radioactive seed placement - discharge ... You had a procedure called brachytherapy to treat prostate cancer. Your treatment lasted 30 minutes or more, ...

  5. Prostate Ultrasound

    Medline Plus

    Full Text Available ... of page Additional Information and Resources RTAnswers.org Radiation Therapy for Prostate Cancer top of page This page was reviewed on March 17, 2016 Send us your feedback Did you find the information you were looking for? ... questions or for a referral to a radiologist or other physician. To locate a medical imaging or radiation oncology provider in your community, you can search ...

  6. Enhancing the Efficacy of Prostate Cancer Immunotherapy by Manipulating T-Cell Receptor Signaling in Order to Alter Peripheral Regulatory T-Cell Activity

    Science.gov (United States)

    2009-07-01

    27] Ross S, Spencer SD, Holcomb I, Tan C, Hongo J, Devaux B, et al. Prostate stem cell antigen as therapy target: tissue expression and in vivo...Holcomb I, Tan C, Hongo J, Devaux B, et al. Prostate stem cell antigen as therapy target: tissue expression and in vivo efficacy of an immunoconjugate

  7. An overview of cancer of the prostate diagnosis and management in ...

    African Journals Online (AJOL)

    Abstract. Objective: To review our experience with cancer of prostate management, highlighting the mode of presentation, method of ... Methods: Medical records of patients managed for cancer of prostate were retrospectively reviewed over a 10-year period. ..... The reason for the late presentation could stem from ignorance ...

  8. Transurethral resection of the prostate

    Science.gov (United States)

    TURP; Prostate resection - transurethral ... used to remove the inside part of your prostate gland using electricity. ... if you have benign prostatic hyperplasia ( BPH ). The prostate gland often grows larger as men get older. ...

  9. Medical Tests for Prostate Problems

    Science.gov (United States)

    ... male urinary tract What are some common prostate problems? The most common prostate problem in men younger ... than BPH. What are the symptoms of prostate problems? The symptoms of prostate problems may include urinary ...

  10. Treatment Option Overview (Prostate Cancer)

    Science.gov (United States)

    ... Prostate Cancer Prostate Cancer Screening Research Prostate Cancer Treatment (PDQ®)–Patient Version General Information About Prostate Cancer ... Certain factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment ...

  11. Unusual Giant Prostatic Urethral Calculus

    African Journals Online (AJOL)

    2010-06-29

    Jun 29, 2010 ... associated with benign prostatic hyperplasia, and prostatic cancer.[1] Primary prostatic urethral calculi are ... Giant vesico-prostatic urethral calculus is uncommon. Urethral stones rarely form primarily in the urethra, ... Prostatic calculi associated with hypertrophy of the gland. Group III. Prostatic calculi that ...

  12. [Benign prostatic hypertrophy and prostate cancer].

    Science.gov (United States)

    Mourey, Loïc; Doumerc, Nicolas; Gaudin, Clément; Gérard, Stéphane; Balardy, Laurent

    2014-01-01

    Prostatic diseases are extremely common, especially in older men. Amongst them, benign prostatic hypertrophy may affect significantly the quality of life of patients by the symptoms it causes. It requires appropriate care. Prostate cancer is the second most common cancer in men after lung cancer and the fifth leading cause of cancer deaths in the world. It affects preferentially older men. An oncogeriatric approach is required for personalised care.

  13. Prostate Cancer Screening

    Science.gov (United States)

    ... treat. There is no standard screening test for prostate cancer. Researchers are studying different tests to find those ... PSA level may be high if you have prostate cancer. It can also be high if you have ...

  14. Prostate cancer staging

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000397.htm Prostate cancer staging To use the sharing features on this ... trials you may be able to join How Prostate Cancer Staging is Done Initial staging is based on ...

  15. Enlarged prostate - after care

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/patientinstructions/000398.htm Enlarged prostate - after care To use the sharing features on this page, please enable JavaScript. The prostate is a gland that produces the fluid that ...

  16. PROSTATE REGULATION: MODELING ENDOGENOUS ...

    Science.gov (United States)

    ALTERATIONS IN PROSTATE WEIGHT AND HISTOPATHOLOGY ARE OBSERVED FOLLOWING IN UTERO, PUBERTAL AND ADULT EXPOSURES TO ANTIANDROGENS. ALTERATIONS IN PROSTATE WEIGHT AND HISTOPATHOLOGY ARE OBSERVED FOLLOWING IN UTERO, PUBERTAL AND ADULT EXPOSURES TO ANTIANDROGENS.

  17. Prostate cancer in Denmark

    DEFF Research Database (Denmark)

    Brasso, K; Friis, S; Kjaer, S K

    1998-01-01

    To review the trends in prostate cancer (PC) incidence and mortality rates in Denmark during a 50-year period.......To review the trends in prostate cancer (PC) incidence and mortality rates in Denmark during a 50-year period....

  18. Benign Prostatic Hyperplasia (BPH)

    Science.gov (United States)

    ... as well as heart disease and use of beta blockers, might increase the risk of BPH. Lifestyle. Obesity ... believed to increase your risk of developing prostate cancer. By Mayo Clinic Staff Benign prostatic hyperplasia (BPH) ...

  19. Enlarged Prostate (BPH)

    Science.gov (United States)

    The prostate is a gland in men. It helps make semen, the fluid that contains sperm. The prostate surrounds the tube that carries urine out of the body. As men age, their prostate grows bigger. If it gets too large, it ...

  20. Original article The Relationship Between Prostate Volume, Prostate ...

    African Journals Online (AJOL)

    mn

    117. 117-123. Original article The Relationship Between Prostate Volume, Prostate-. Specific Antigen and Age in Saudi Men with Benign. Prostatic Conditions. H. A. Mosli1 and ... Methods: Medical records of 447 Saudi men aged 20-89 years with benign prostatic conditions .... widely used to identify an enlarged prostate,.

  1. Ultrasound- and MRI-Guided Prostate Biopsy

    Science.gov (United States)

    ... Resources Professions Site Index A-Z Ultrasound- and MRI-Guided Prostate Biopsy Ultrasound- and MRI-guided prostate ... MRI-guided Prostate Biopsy? What is Ultrasound- and MRI-guided Prostate Biopsy? Ultrasound- and MRI-guided prostate ...

  2. Prostate-Specific Antigen (PSA) Test

    Science.gov (United States)

    ... Genetics of Prostate Cancer Prostate Cancer Screening Research Prostate-Specific Antigen (PSA) Test On This Page What ... the PSA test for prostate cancer screening? Detecting prostate cancer early may not reduce the chance of ...

  3. Monosodium glutamate: Potentials at inducing prostate pathologies ...

    African Journals Online (AJOL)

    ONOS

    2010-09-06

    Sep 6, 2010 ... either MSG or DW. Key words: Monosodium glutamate, total acid phosphatase, prostatic acid phosphatase, prostate cancer, prostatitis, benign prostate hyperplasia, infertility. INTRODUCTION. Elevated total acid phosphatase (TAP) and prostatic acid phosphatase (PAP) activities are among the main.

  4. Types of Stem Cells

    Science.gov (United States)

    ... Stem Cell Glossary Search Toggle Nav Types of Stem Cells Stem cells are the foundation from which all ... Learn About Stem Cells > Types of Stem Cells Stem cells Stem cells are the foundation for every organ ...

  5. Genetic and epigenetic stability of human spermatogonial stem cells during long-term culture

    NARCIS (Netherlands)

    Nickkholgh, Bita; Mizrak, S. Canan; van Daalen, Saskia K. M.; Korver, Cindy M.; Sadri-Ardekani, Hooman; Repping, Sjoerd; van Pelt, Ans M. M.

    2014-01-01

    To determine the genetic and epigenetic stability of human spermatogonial stem cells (SSCs) during long-term culture. Experimental basic science study. Reproductive biology laboratory. Cryopreserved human testicular tissue from two prostate cancer patients with normal spermatogenesis. None.

  6. Prostate cancer

    DEFF Research Database (Denmark)

    Elkjær, Maria Carlsen; Andersen, Morten Heebøll; Høyer, Søren

    2017-01-01

    Background Active surveillance (AS) of low-risk prostate cancer (PCa) is an accepted alternative to active treatment. However, the conventional diagnostic trans-rectal ultrasound guided biopsies (TRUS-bx) underestimate PCa aggressiveness in almost half of the cases, when compared with the surgical...... lesions. Significant cancer was defined as GS > 6 or GS 6 (3 + 3) lesions with ≥ 6 mm maximal cancer core length (MCCL). Results A total of 78 patients were included and in 21 patients a total of 22 PIRADS-score 4 or 5 lesions were detected. MRGB pathology revealed that 17 (81%) of these and 22......% of the entire AS population harbored significant cancers at AS inclusion. In eight (38%) cases, the GS was upgraded. Also, nine patients (43%) had GS 6 (3 + 3) foci with MCCL ≥ 6 mm. Conclusion In an AS cohort based on TRUS and TRUS-bx diagnostic strategies, supplemental mpMRI and in-bore MRGB were able...

  7. 6 Common Cancers - Prostate Cancer

    Science.gov (United States)

    ... Bar Home Current Issue Past Issues 6 Common Cancers - Prostate Cancer Past Issues / Spring 2007 Table of Contents ... early screening. Photo: AP Photo/Danny Moloshok Prostate Cancer The prostate gland is a walnut-sized structure that makes ...

  8. Hormone therapy for prostate cancer

    Science.gov (United States)

    ... gov/ency/patientinstructions/000908.htm Hormone therapy for prostate cancer To use the sharing features on this page, ... the growth of prostate cancer. Male Hormones and Prostate Cancer Androgens are male sex hormones. Testosterone is one ...

  9. DIFFERENTIAL DIAGNOSTICS OF PROSTATE TUBERCULOSIS

    Directory of Open Access Journals (Sweden)

    E. V. Brizhatyuk

    2017-01-01

    Full Text Available Prostate tuberculosis is difficult to be diagnosed, especially if lesions are limited only by this organ. The article analyses the experience of differential diagnostics of prostate tuberculosis based on the data of examination of 84 patients. 45 of them were diagnosed with prostate tuberculosis, and 39 patients were diagnosed with chronic bacterial prostatitis. Pathognomonic diagnostics criteria of prostate tuberculosis were the following: detection of tuberculous mycobacteria in the prostatic fluid or ejaculate, signs of granulomatous prostatitis with areas of cavernous necrosis in prostate biopsy samples, and prostate cavities visualized by X-ray or ultrasound examinations. Should the above criteria be absent, the disease can be diagnosed based on the combination of indirect signs: symptoms of prostate inflammation with active tuberculosis of the other localization; large prostate calcification, extensive hyperechoic area of the prostate, spermatocystic lesions, leucospermia and hemospermia, failure of the adequate non-specific anti-bacterial therapy.

  10. Prostatic Disease and Sexual Dysfunction

    OpenAIRE

    Kim, Sae Woong

    2011-01-01

    Prostatitis and benign prostatic hyperplasia (BPH) are common prostatic diseases. Furthermore, the incidence of prostate cancer has recently shown a rapid increase, even in Korea. Pain caused by prostatitis may induce sexual dysfunction, including erectile dysfunction and ejaculatory disturbance. And BPH itself, or treatments for BPH, may affect sexual function. In addition, with increased detection of localized prostate cancer, surgical treatments and radiation therapy have also increased, a...

  11. Prostate specific antigen in patients of benign prostate hypertrophy and carcinoma prostate

    OpenAIRE

    Malati, T.; Kumari, G. Rajani; Murthy, P. V. L. N.; Reddy, Ch.Ram; Prakash, B. Surya

    2006-01-01

    Prostate Specific Antigen (PSA) has emerged as the most applicable and important tumor marker for carcinoma prostate. In the present study PSA was determined in serum of healthy subjects, patients of benign prostate hypertrophy (BPH) and Carcinoma Prostate (Ca−P) to evaluate its diagnostic efficiency in day to day management of prostate cancer patients and in differentiating patients of early prostate cancer from those with BPH. Receiver operating characteristic curve (ROC) revealed 2 ng/ml a...

  12. Danish Prostate Cancer Registry

    DEFF Research Database (Denmark)

    Helgstrand, J Thomas; Klemann, Nina; Røder, Martin Andreas

    2016-01-01

    of the prostate (TUR-Ps), and the remaining 22,028 (13.6%) specimens were derived from radical prostatectomies, bladder interventions, etc. A total of 48,078 (42.2%) males had histopathologically verified prostate cancer, and of these, 78.8% and 16.8% were diagnosed on prostate biopsies and TUR-Ps, respectively....... FUTURE PERSPECTIVES: A validated algorithm was successfully developed to convert complex prostate SNOMED codes into clinical useful data. A unique database, including males with both normal and cancerous histopathological data, was created to form the most comprehensive national prostate database to date......BACKGROUND: Systematized Nomenclature of Medicine (SNOMED) codes are computer-processable medical terms used to describe histopathological evaluations. SNOMED codes are not readily usable for analysis. We invented an algorithm that converts prostate SNOMED codes into an analyzable format. We...

  13. [Epigenetics of prostate cancer].

    Science.gov (United States)

    Yi, Xiao-Ming; Zhou, Wen-Quan

    2010-07-01

    Prostate cancer is one of the most common malignant tumors in males, and its etiology and pathogenesis remain unclear. Epigenesis is involved in prostate cancer at all stages of the process, and closely related with its growth and metastasis. DNA methylation and histone modification are the most important manifestations of epigenetics in prostate cancer. The mechanisms of carcinogenesis of DNA methylation include whole-genome hypomethylation, aberrant local hypermethylation of promoters and genomic instability. DNA methylation is closely related to the process of prostate cancer, as in DNA damage repair, hormone response, tumor cell invasion/metastasis, cell cycle regulation, and so on. Histone modification causes corresponding changes in chromosome structure and the level of gene transcription, and it may affect the cycle, differentiation and apoptosis of cells, resulting in prostate cancer. Some therapies have been developed targeting the epigenetic changes in prostate cancer, including DNA methyltransferases and histone deacetylase inhibitors, and have achieved certain desirable results.

  14. Prostate carcinomas; Cancer de la prostate

    Energy Technology Data Exchange (ETDEWEB)

    Toledano, A.; Chauveinc, L.; Flam, T.; Thiounn, N.; Solignac, S.; Timbert, M.; Rosenwald, J.C.; Cosset, J.M.; Ammor, A.; Bonnetain, F.; Brenier, J.P.; Maingon, P.; Peignaux, K.; Truc, G.; Bosset, M.; Crevoisier, R. de; Tucker, S.; Dong, L.; Cheung, R.; Kuban, D.; Azria, D.; Llacer Moscardo, C.; Ailleres, N.; Allaw, A.; Serre, A.; Fenoglietto, P.; Hay, M.H.; Thezenas, S.; Dubois, J.B.; Pommier, P.; Perol, D.; Lagrange, J.L.; Richaud, P.; Brune, D.; Le Prise, E.; Azria, D.; Beckendorf, V.; Chabaud, S.; Carrie, C.; Bosset, M.; Bosset, J.F.; Maingon, P.; Ammor, A.; Crehangen, G.; Truc, G.; Peignaux, K.; Bonnetain, F.; Keros, L.; Bernier, V.; Aletti, P.; Wolf, D.; Marchesia, V.; Noel, A.; Artignan, X.; Fourneret, P.; Bacconier, M.; Shestaeva, O.; Pasquier, D.; Descotes, J.L.; Balosso, J.; Bolla, M.; Burette, R.; Corbusier, A.; Germeau, F.; Crevoisier, R. de; Dong, L.; Bonnen, M.; Cheung, R.; Tucker, S.; Kuban, D.; Crevoisier, R. de; Melancon, A.; Kuban, D.; Cheung, R.; Dong, L.; Peignaux, K.; Brenier, J.P.; Truc, G.; Bosset, M.; Ammor, A.; Barillot, I.; Maingon, P.; Molines, J.C.; Berland, E.; Cornulier, J. de; Coulet-Parpillon, A.; Cohard, C.; Picone, M.; Fourneret, P.; Artignan, X.; Daanen, V.; Gastaldo, J.; Bolla, M.; Collomb, D.; Dusserre, A.; Descotes, J.L.; Troccaz, J.; Giraud, J.Y.; Quero, L.; Hennequin, C.; Ravery, V.; Desgrandschamps, F.; Maylin, C.; Boccon-Gibod, L.; Salem, N.; Bladou, F.; Gravis, G.; Tallet, A.; Simonian, M.; Serment, G.; Salem, N.; Bladou, F.; Gravis, G.; Simonian, M.; Rosello, R.; Serment, G

    2005-11-15

    Some short communications on the prostate carcinoma are given here. The impact of pelvic irradiation, conformation with intensity modulation, association of radiotherapy and chemotherapy reduction of side effects, imaging, doses escalation are such subjects studied and reported. (N.C.)

  15. Prostate progenitor cells proliferate in response to castration

    Directory of Open Access Journals (Sweden)

    Xudong Shi

    2014-07-01

    Full Text Available Androgen-deprivation is a mainstay of therapy for advanced prostate cancer but tumor regression is usually incomplete and temporary because of androgen-independent cells in the tumor. It has been speculated that these tumor cells resemble the stem/progenitor cells of the normal prostate. The purpose of this study was to examine the response of slow-cycling progenitor cells in the adult mouse prostate to castration. Proliferating cells in the E16 urogenital sinus were pulse labeled by BrdU administration or by doxycycline-controlled labeling of the histone-H2B GFP mouse. A small population of labeled epithelial cells in the adult prostate localized at the junction of the prostatic ducts and urethra. Fluorescence-activated cell sorting (FACS showed that GFP label-retaining cells were enriched for cells co-expressing stem cell markers Sca-1, CD133, CD44 and CD117 (4- marker cells; 60-fold enrichment. FACS showed, additionally, that 4-marker cells were androgen receptor positive. Castration induced proliferation and dispersal of E16 labeled cells into more distal ductal segments. When naïve adult mice were administered BrdU daily for 2 weeks after castration, 16% of 4-marker cells exhibited BrdU label in contrast to only 6% of all epithelial cells (P < 0.01. In sham-castrated controls less than 4% of 4-marker cells were BrdU labeled (P < 0.01. The unexpected and admittedly counter-intuitive finding that castration induced progenitor cell proliferation suggests that androgen deprivation therapy in men with advanced prostate cancer could not only exert pleiotrophic effects on tumor sub-populations but may induce inadvertent expansion of tumor stem cells.

  16. Review article: Prostate cancer screening using prostate specific ...

    African Journals Online (AJOL)

    Background: Prostate cancer is the commonest cancer among men in Nigeria and early detection is key to cure and survival but its screening through prostate specific antigen (PSA) has remain controversial in literature. Screening with prostate specific antigen (PSA) has led to more men diagnosed with prostate cancer than ...

  17. Prostate specific antigen: a useful but limited marker for prostate ...

    African Journals Online (AJOL)

    238 CME July 2012 Vol. 30 No. 7. Prostate specific antigen: a useful but limited marker for prostate cancer. Prostate specific antigen is widely used as a tumour marker for prostate cancer. K B Sedumedi, BSc, MB ChB, MMed (Chem Path). Senior Specialist/Lecturer, Department of Chemical Pathology, University of Limpopo, ...

  18. Conventional prostatic adenocarcinoma arising in a multilocular prostatic cystadenoma.

    Science.gov (United States)

    Lee, Thomas K; Chuang, Shang-Tian; Netto, George J

    2010-05-01

    Multilocular prostatic cystadenoma is a rare benign neoplasm located between the bladder and the rectum. These are prostatic tissue and have been shown to harbor high-grade intraepithelial neoplasia and likely susceptible to the same disease processes seen in the prostate gland. We report the first case of conventional prostatic adenocarcinoma involving a multilocular cystadenoma. Distinction from cystadenocarcinoma is also made.

  19. Ecotropic viral integration site 1, a novel oncogene in prostate cancer.

    Science.gov (United States)

    Queisser, A; Hagedorn, S; Wang, H; Schaefer, T; Konantz, M; Alavi, S; Deng, M; Vogel, W; von Mässenhausen, A; Kristiansen, G; Duensing, S; Kirfel, J; Lengerke, C; Perner, S

    2017-03-01

    Prostate cancer (PCa) is the most commonly diagnosed non-cutaneous cancer in men in the western world. Mutations in tumor suppressor genes and in oncogenes are important for PCa progression, whereas the role of stem cell proteins in prostate carcinogenesis is insufficiently examined. This study investigates the role of the transcriptional regulator Ecotropic Viral Integration site 1 (EVI1), known as an essential modulator of hematopoietic and leukemic stem cell biology, in prostate carcinogenesis. We show that in healthy prostatic tissue, EVI1 expression is confined to the prostate stem cell compartment located at the basal layer, as identified by the stem cell marker CD44. Instead, in a PCa progression cohort comprising 219 samples from patients with primary PCa, lymph node and distant metastases, EVI1 protein was heterogeneously distributed within samples and high expression is associated with tumor progression (P<0.001), suggesting EVI1 induction as a driver event. Functionally, short hairpin RNA-mediated knockdown of EVI1 inhibited proliferation, cell cycle progression, migratory capacity and anchorage-independent growth of human PCa cells, while enhancing their apoptosis sensitivity. Interestingly, modulation of EVI1 expression also strongly regulated stem cell properties (including expression of the stem cell marker SOX2) and in vivo tumor initiation capacity. Further emphasizing a functional correlation between EVI1 induction and tumor progression, upregulation of EVI1 expression was noted in experimentally derived docetaxel-resistant PCa cells. Importantly, knockdown of EVI1 in these cells restored sensitivity to docetaxel, in part by downregulating anti-apoptotic BCL2. Together, these data indicate EVI1 as a novel molecular regulator of PCa progression and therapy resistance that may control prostate carcinogenesis at the stem cell level.

  20. Stem Cells

    Directory of Open Access Journals (Sweden)

    Madhukar Thakur

    2015-02-01

    Full Text Available Objective: The objective of this presentation is to create awareness of stem cell applications in the ISORBE community and to foster a strategy of how the ISORBE community can disseminate information and promote the use of radiolabeled stem cells in biomedical applications. Methods: The continued excitement in Stem Cells, in many branches of basic and applied biomedical science, stems from the remarkable ability of stem cells to divide and develop into different types of cells in the body. Often called as Magic Seeds, stem cells are produced in bone marrow and circulate in blood, albeit at a relatively low concentration. These virtues together with the ability of stem cells to grow in tissue culture have paved the way for their applications to generate new and healthy tissues and to replace diseased or injured human organs. Although possibilities of stem cell applications are many, much remains yet to be understood of these remarkable magic seeds. Conclusion: This presentation shall briefly cover the origin of stem cells, the pros and cons of their growth and division, their potential application, and shall outline some examples of the contributions of radiolabeled stem cells, in this rapidly growing branch of biomedical science

  1. Estrogen receptors in the human male prostatic urethra and prostate in prostatic cancer and benign prostatic hyperplasia

    DEFF Research Database (Denmark)

    Bødker, A; Bruun, J; Balslev, E

    1999-01-01

    demonstrated in the prostatic stroma and/or prostatic urethra in 6 out of 11 cases. In both BPH and PC patients, immunoreactivity was weak and confined to few cells, indicating low ER content in the prostate as well as in the prostatic urethra. Dextran-coated charcoal (DCC) analysis was used for detection...

  2. The Prostate Exam

    Science.gov (United States)

    Romero, Frederico R.; Romero, Antonio W.; Filho, Thadeu Brenny; Kulysz, David; Oliveira, Fernando C., Jr.; Filho, Renato Tambara

    2012-01-01

    Objective: To help students, residents, and general practitioners to improve the technique, skills, and reproducibility of their prostate examination. Methods: We developed a comprehensive guideline outlining prostate anatomy, indications, patient preparation, positioning, technique, findings, and limitations of this ancient art of urological…

  3. [Transrectal prostatic sonography (TPS)].

    Science.gov (United States)

    Frentzel-Beyme, B; Schwartz, J; Aurich, B

    1982-06-01

    A new imaging method of the prostate is described. After the introduction of a sonographic transducer into the rectum, the prostate, the urinary bladder and the seminal vesicles are scanned. Typical transverse sonograms of benign hypertrophy, abscess, calculous disease and carcinomas are presented. The value of this method and its indications are discussed.

  4. Chronic bacterial prostatitis in men with spinal cord injury.

    Science.gov (United States)

    Krebs, Jörg; Bartel, Peter; Pannek, Jürgen

    2014-12-01

    Recurrent urinary tract infections (UTI) are a major problem affecting spinal cord injury (SCI) patients and may stem from chronic bacterial prostatitis. We have therefore investigated the presence of chronic bacterial prostatitis and its role in the development of recurrent symptomatic UTI in SCI men. This study is a prospective cross-sectional investigation of bacterial prostatitis in SCI men in a single SCI rehabilitation center. In 50 men with chronic SCI presenting for a routine urologic examination, urine samples before and after prostate massage were taken for microbiologic investigation and white blood cell counting. Furthermore, patient characteristics, bladder diary details, and the annual rate of symptomatic UTI were collected retrospectively. No participant reported current symptoms of UTI or prostatitis. In most men (39/50, 78 %), the microbiologic analysis of the post-massage urine sample revealed growth of pathogenic bacteria. The majority of these men (32/39, 82 %) also presented with mostly (27/39, 69 %) the same pathogenic bacteria in the pre-massage sample. There was no significant (p = 0.48) difference in the number of symptomatic UTI in men with a positive post-massage culture compared with those with a negative culture. No significant (p = 0.67) difference in the frequency distribution of positive versus negative post-massage cultures was detected between men with recurrent and sporadic UTI. Most SCI men are affected by asymptomatic bacterial prostatitis; however, bacterial prostatitis does not play a major role in the development of recurrent UTI. The indication for antibiotic treatment of chronic bacterial prostatitis in asymptomatic SCI men with recurrent UTI is questionable.

  5. Treatment Options by Stage (Prostate Cancer)

    Science.gov (United States)

    ... Prostate Cancer Prostate Cancer Screening Research Prostate Cancer Treatment (PDQ®)–Patient Version General Information About Prostate Cancer ... Certain factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment ...

  6. Cell kinetic studies fail to identify sequentially proliferating progenitors as the major source of epithelial renewal in the adult murine prostate.

    Directory of Open Access Journals (Sweden)

    Jean-Christophe Pignon

    Full Text Available There is evidence that stem cells and their progeny play a role in the development of the prostate. Although stem cells are also considered to give rise to differentiated progeny in the adult prostate epithelium ex vivo, the cohort of adult prostate stem cells in vivo as well as the mechanisms by which the adult prostate epithelium is maintained and regenerated remain highly controversial. We have attempted to resolve this conundrum by performing in vivo tracing of serially replicating cells after the sequential administration of two thymidine analogues to mice. Our results show that, during normal prostate homeostasis, sequentially proliferating cells are detected at a rate that is consistent with a stochastic process. These findings indicate that in vivo, under steady-state conditions, most adult prostate epithelial cells do not represent the progeny of a small number of specialized progenitors that generate sequentially replicating transit-amplifying (TA cells but are formed by stochastic cell division. Similarly, no rapidly cycling TA cells were detected during regeneration following one cycle of androgen-mediated involution/regeneration of the prostate epithelium. These findings greatly enhance our understanding of the mechanisms regulating prostate epithelial cell renewal and may have significant implications in defining the cell of origin of proliferative prostatic diseases.

  7. Cell kinetic studies fail to identify sequentially proliferating progenitors as the major source of epithelial renewal in the adult murine prostate.

    Science.gov (United States)

    Pignon, Jean-Christophe; Grisanzio, Chiara; Carvo, Ingrid; Werner, Lillian; Regan, Meredith; Wilson, E Lynette; Signoretti, Sabina

    2015-01-01

    There is evidence that stem cells and their progeny play a role in the development of the prostate. Although stem cells are also considered to give rise to differentiated progeny in the adult prostate epithelium ex vivo, the cohort of adult prostate stem cells in vivo as well as the mechanisms by which the adult prostate epithelium is maintained and regenerated remain highly controversial. We have attempted to resolve this conundrum by performing in vivo tracing of serially replicating cells after the sequential administration of two thymidine analogues to mice. Our results show that, during normal prostate homeostasis, sequentially proliferating cells are detected at a rate that is consistent with a stochastic process. These findings indicate that in vivo, under steady-state conditions, most adult prostate epithelial cells do not represent the progeny of a small number of specialized progenitors that generate sequentially replicating transit-amplifying (TA) cells but are formed by stochastic cell division. Similarly, no rapidly cycling TA cells were detected during regeneration following one cycle of androgen-mediated involution/regeneration of the prostate epithelium. These findings greatly enhance our understanding of the mechanisms regulating prostate epithelial cell renewal and may have significant implications in defining the cell of origin of proliferative prostatic diseases.

  8. Testosterone levels in benign prostatic hypertrophy and prostate cancer.

    Science.gov (United States)

    Mearini, Luigi; Costantini, Elisabetta; Zucchi, Alessandro; Mearini, Ettore; Bini, Vittorio; Cottini, Emanuele; Porena, Massimo

    2008-01-01

    Although hormones play fundamental roles in prostate growth, their clinical significance is not completely clear. In the present study we assessed whether serum hormone levels are markers of prostate disease. In 128 patients with benign prostatic hypertrophy or prostate cancer, testosterone, follicle-stimulating hormone, luteinizing hormone, and prolactin levels were correlated with disease. In patients with prostate cancer, the hormone levels were also correlated with prognostic factors. Predictive values were assessed for prostate-specific antigen and testosterone levels only, using multiple logistic regression analysis and receiver operating characteristic curves. The testosterone concentrations were significantly lower in patients with prostate cancer than in those with benign prostatic hypertrophy and were also significantly lower in patients with advanced-stage disease than in patients with organ-confined disease. Testosterone appears to be an independent predictor of disease and enhances the predictive accuracy for benign prostatic hypertrophy and prostate cancer. This study supports experimental findings that prostate cancer is frequently associated with low testosterone concentrations. In the diagnostic workup for prostate cancer, associating prostate-specific antigen and testosterone levels may improve the predictive accuracy of prostate disease tests.

  9. Proteomic Study of HPV-Positive Head and Neck Cancers: Preliminary Results

    Directory of Open Access Journals (Sweden)

    Géraldine Descamps

    2014-01-01

    Full Text Available Human papillomavirus (HPV was recently recognized as a new risk factor for head and neck squamous cell carcinoma. For oropharyngeal cancers, an HPV+ status is associated with better prognosis in a subgroup of nonsmokers and nondrinkers. However, HPV infection is also involved in the biology of head and neck carcinoma (HNC in patients with a history of tobacco use and/or alcohol consumption. Thus, the involvement of HPV infection in HN carcinogenesis remains unclear, and further studies are needed to identify and analyze HPV-specific pathways that are involved in this process. Using a quantitative proteomics-based approach, we compared the protein expression profiles of two HPV+ HNC cell lines and one HPV− HNC cell line. We identified 155 proteins that are differentially expressed (P<0.01 in these three lines. Among the identified proteins, prostate stem cell antigen (PSCA was upregulated and eukaryotic elongation factor 1 alpha (EEF1α was downregulated in the HPV+ cell lines. Immunofluorescence and western blotting analyses confirmed these results. Moreover, PSCA and EEF1α were differentially expressed in two clinical series of 50 HPV+ and 50 HPV− oral cavity carcinomas. Thus, our study reveals for the first time that PSCA and EEF1α are associated with the HPV-status, suggesting that these proteins could be involved in HPV-associated carcinogenesis.

  10. STEM Education.

    Science.gov (United States)

    Xie, Yu; Fang, Michael; Shauman, Kimberlee

    2015-08-01

    Improving science, technology, engineering, and mathematics (STEM) education, especially for traditionally disadvantaged groups, is widely recognized as pivotal to the U.S.'s long-term economic growth and security. In this article, we review and discuss current research on STEM education in the U.S., drawing on recent research in sociology and related fields. The reviewed literature shows that different social factors affect the two major components of STEM education attainment: (1) attainment of education in general, and (2) attainment of STEM education relative to non-STEM education conditional on educational attainment. Cognitive and social psychological characteristics matter for both major components, as do structural influences at the neighborhood, school, and broader cultural levels. However, while commonly used measures of socioeconomic status (SES) predict the attainment of general education, social psychological factors are more important influences on participation and achievement in STEM versus non-STEM education. Domestically, disparities by family SES, race, and gender persist in STEM education. Internationally, American students lag behind those in some countries with less economic resources. Explanations for group disparities within the U.S. and the mediocre international ranking of US student performance require more research, a task that is best accomplished through interdisciplinary approaches.

  11. Stem Cells

    DEFF Research Database (Denmark)

    Sommerlund, Julie

    2004-01-01

    '. This paper is about tech-noscience, and about the proliferation of connections and interdependencies created by it.More specifically, the paper is about stem cells. Biotechnology in general has the power to capture the imagination. Within the field of biotechnology nothing seems more provocative...... and tantalizing than stem cells, in research, in medicine, or as products....

  12. Methods for Prostate Biopsy

    OpenAIRE

    M. Ghafoori

    2008-01-01

    Prostate cancer is currently the most prevalent form of cancer in men and the second leading cause of can-cer death in the United States, and the third most common cancer in men worldwide. Increasing mor-tality rates due to prostate carcinoma have been ob-served worldwide. This disease usually progresses im-perceptibly; thus, patients are unlikely to seek medi-cal help during the early stages. For these reasons, screening programs aimed at early detection have been developed. The prostate-spe...

  13. Learn About Stem Cells

    Science.gov (United States)

    ... Patient Handbook Stem Cell Glossary Search Toggle Nav Stem Cell Basics Stem cells are the foundation from which ... original cell’s DNA, cytoplasm and cell membrane. About stem cells Stem cells are the foundation of development in ...

  14. Molecular imaging of prostate cancer: translating molecular biology approaches into the clinical realm.

    Science.gov (United States)

    Vargas, Hebert Alberto; Grimm, Jan; F Donati, Olivio; Sala, Evis; Hricak, Hedvig

    2015-05-01

    The epidemiology of prostate cancer has dramatically changed since the introduction of prostate-specific antigen (PSA) screening in the 1980's. Most prostate cancers today are detected at early stages of the disease and are considered 'indolent'; however, some patients' prostate cancers demonstrate a more aggressive behaviour which leads to rapid progression and death. Increasing understanding of the biology underlying the heterogeneity that characterises this disease has led to a continuously evolving role of imaging in the management of prostate cancer. Functional and metabolic imaging techniques are gaining importance as the impact on the therapeutic paradigm has shifted from structural tumour detection alone to distinguishing patients with indolent tumours that can be managed conservatively (e.g., by active surveillance) from patients with more aggressive tumours that may require definitive treatment with surgery or radiation. In this review, we discuss advanced imaging techniques that allow direct visualisation of molecular interactions relevant to prostate cancer and their potential for translation to the clinical setting in the near future. The potential use of imaging to follow molecular events during drug therapy as well as the use of imaging agents for therapeutic purposes will also be discussed. • Advanced imaging techniques allow direct visualisation of molecular interactions in prostate cancer. • MRI/PET, optical and Cerenkov imaging facilitate the translation of molecular biology. • Multiple compounds targeting PSMA expression are currently undergoing clinical translation. • Other targets (e.g., PSA, prostate-stem cell antigen, GRPR) are in development.

  15. Yes-Associated Protein Expression Is Correlated to the Differentiation of Prostate Adenocarcinoma.

    Science.gov (United States)

    Noh, Myung-Giun; Kim, Sung Sun; Hwang, Eu Chang; Kwon, Dong Deuk; Choi, Chan

    2017-07-01

    Yes-associated protein (YAP) in the Hippo signaling pathway is a growth control pathway that regulates cell proliferation and stem cell functions. Abnormal regulation of YAP was reported in human cancers including liver, lung, breast, skin, colon, and ovarian cancer. However, the function of YAP is not known in prostate adenocarcinoma. The purpose of this study was to investigate the role of YAP in tumorigenesis, differentiation, and prognosis of prostate adenocarcinoma. The nuclear and cytoplasmic expression of YAP was examined in 188 cases of prostate adenocarcinoma using immunohistochemistry. YAP expression levels were evaluated in the nucleus and cytoplasm of the prostate adenocarcinoma and the adjacent normal prostate tissue. The presence of immunopositive tumor cells was evaluated and interpreted in comparison with the patients' clinicopathologic data. YAP expression levels were not significantly different between normal epithelial cells and prostate adenocarcinoma. However, YAP expression level was significantly higher in carcinomas with a high Gleason grades (8-10) than in carcinomas with a low Gleason grades (6-7) (p < .01). There was no statistical correlation between YAP expression and stage, age, prostate-specific antigen level, and tumor volume. Biochemical recurrence (BCR)-free survival was significantly lower in patients with high YAP expressing cancers (p = .02). However high YAP expression was not an independent prognostic factor for BCR in the Cox proportional hazards model. The results suggested that YAP is not associated with prostate adenocarcinoma development, but it may be associated with the differentiation of the adenocarcinoma. YAP was not associated with BCR.

  16. GP140/CDCPI in the Development of Prostate Cancer Metastasis

    Science.gov (United States)

    2013-09-01

    Biosciences, San Jose , CA) and FloJo (Tree Star Inc., Ashland, OR) software. Matrigel Three-Dimensional Culture Cells were cultured in eight-well...Kong D, Banerjee S, Ahmad A, Li Y, Wang Z, Sethi S, Sarkar FH: Epithelial to mesenchymal transition is mechanistically linked with stem cell...cadherin is reduced or absent in high-grade prostate cancer. Cancer Res 1992, 52:5104–5109 28. Pontes J Jr, Srougi M, Borra PM, Dall’ Oglio MF, Ribeiro -Filho

  17. About the Prostate

    Science.gov (United States)

    ... Control Text: Please leave this field empty Normal Physiology The prostate is not essential for life, but is important for reproduction. It supplies substances that facilitate fertilization and sperm ...

  18. Epigenetics in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Costantine Albany

    2011-01-01

    Full Text Available Prostate cancer (PC is the most commonly diagnosed nonskin malignancy and the second most common cause of cancer death among men in the United States. Epigenetics is the study of heritable changes in gene expression caused by mechanisms other than changes in the underlying DNA sequences. Two common epigenetic mechanisms, DNA methylation and histone modification, have demonstrated critical roles in prostate cancer growth and metastasis. DNA hypermethylation of cytosine-guanine (CpG rich sequence islands within gene promoter regions is widespread during neoplastic transformation of prostate cells, suggesting that treatment-induced restoration of a “normal” epigenome could be clinically beneficial. Histone modification leads to altered tumor gene function by changing chromosome structure and the level of gene transcription. The reversibility of epigenetic aberrations and restoration of tumor suppression gene function have made them attractive targets for prostate cancer treatment with modulators that demethylate DNA and inhibit histone deacetylases.

  19. Learning about Prostate Cancer

    Science.gov (United States)

    ... gov] There are companies that will soon be marketing and selling genetic tests that will predict a ... enzyme made by the prostate gland, and a digital rectal examination (DRE) are two tests that are ...

  20. Sarcoidosis of the prostate

    OpenAIRE

    Furusato, Bungo; Koff, Stacey; McLeod, David G; Sesterhenn, Isabell A

    2007-01-01

    A 55‐year‐old African‐American man with clinical stage T1c prostate cancer underwent prostatectomy. Non‐caseating, epithelioid granulomata adjacent to the anterior fibromuscular stroma were found incidentally. The granulomata included Langhans giant cells with rare conchoidal bodies. The distribution of the granulomata was not that of non‐specific granulomatous prostatitis centred around ducts and glands. By immunohistochemistry, the epithelioid cells were positive for angiotensin‐converting ...

  1. Injectables in the prostate.

    Science.gov (United States)

    Saemi, Arash M; Plante, Mark K

    2008-01-01

    Benign prostatic hyperplasia with associated symptoms and morbidity is increasingly common among aging men. Medical treatment of lower urinary tract symptoms is the mainstay of therapy with progressive disease requiring more invasive intervention. Transurethral resection of the prostate remains a widely applied gold standard therapy. Numerous minimally invasive surgical therapy options have arisen and subsequently faded over recent years. Those remaining in use are largely positioned between pharmacological treatment and transurethral resection of the prostate. Intraprostatic injection therapy, the oldest minimally invasive surgical therapy, has been investigated for over 100 years with renewed interest recently. This review will provide some history of intraprostatic injection for benign prostatic hyperplasia including the most recent reports using transperineal, transrectal and transurethral routes with different injectables. For benign prostatic hyperplasia, transperineal and transurethral injection routes have received the most systematic evaluation. Intraprostatic injection of botulinum toxin type A has received much recent attention with regards to mechanism of action and efficacy. Anhydrous ethanol remains the most extensively studied injectable to date. Injection therapy remains a very promising minimally invasive surgical therapy for benign prostatic hyperplasia with increased attention from the urologic community in recent years. Further experience both with systematic laboratory and clinical trials investigation will be necessary before widespread clinical adoption.

  2. Targeted prodrug approaches for hormone refractory prostate cancer.

    Science.gov (United States)

    Aloysius, Herve; Hu, Longqin

    2015-05-01

    Due to the propensity of relapse and resistance with prolonged androgen deprivation therapy (ADT), there is a growing interest in developing non-hormonal therapeutic approaches as alternative treatment modalities for hormone refractory prostate cancer (HRPC). Although the standard treatment for HRPC consists of a combination of ADT with taxanes and anthracyclines, the clinical use of chemotherapeutics is limited by systemic toxicity stemming from nondiscriminatory drug exposure to normal tissues. In order to improve the tumor selectivity of chemotherapeutics, various targeted prodrug approaches have been explored. Antibody-directed enzyme prodrug therapy (ADEPT) and gene-directed enzyme prodrug therapy (GDEPT) strategies leverage tumor-specific antigens and transcription factors for the specific delivery of cytotoxic anticancer agents using various prodrug-activating enzymes. In prostate cancer, overexpression of tumor-specific proteases such as prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) is being exploited for selective activation of anticancer prodrugs designed to be activated through proteolysis by these prostate cancer-specific enzymes. PSMA- and PSA-activated prodrugs typically comprise an engineered high-specificity protease peptide substrate coupled to a potent cytotoxic agent via a linker for rapid release of cytotoxic species in the vicinity of prostate cancer cells following proteolytic cleavage. Over the past two decades, various such prodrugs have been developed and they were effective at inhibiting prostate tumor growth in rodent models; several of these prodrug approaches have been advanced to clinical trials and may be developed into effective therapies for HRPC. © 2014 Wiley Periodicals, Inc.

  3. The link between benign prostatic hyperplasia and prostate cancer

    DEFF Research Database (Denmark)

    Ørsted, David Dynnes; Bojesen, Stig E

    2013-01-01

    Benign prostatic hyperplasia (BPH) and prostate cancer are among the most common diseases of the prostate gland and represent significant burdens for patients and health-care systems in many countries. The two diseases share traits such as hormone-dependent growth and response to antiandrogen...

  4. New Prostate Cancer Treatment Target

    Science.gov (United States)

    Researchers have identified a potential alternative approach to blocking a key molecular driver of an advanced form of prostate cancer, called androgen-independent or castration-resistant prostate cancer.

  5. Hyaluronan Biosynthesis in Prostate Cancer

    National Research Council Canada - National Science Library

    McCarthy, James B

    2006-01-01

    Despite advances in the diagnosis and treatment of prostate cancer in the last several years metastasis represents the major cause of frustration and failure in the successful treatment of prostate cancer patients. Hyaluronan (HA...

  6. Center for Prostate Disease Research

    Data.gov (United States)

    Federal Laboratory Consortium — The Center for Prostate Disease Research is the only free-standing prostate cancer research center in the U.S. This 20,000 square foot state-of-the-art basic science...

  7. Paracrine Regulation of Prostatic Carcinogenesis

    National Research Council Canada - National Science Library

    Hayward, Simon

    2003-01-01

    .... The objective of the proposed research is to establish immortalized stromal cell lines derived from normal human prostate and from human prostate cancer and to use these cells to investigate the role...

  8. Overdetection, overtreatment and costs in prostate-specific antigen screening for prostate cancer

    NARCIS (Netherlands)

    E.A.M. Heijnsdijk (Eveline); A. der Kinderen (Arno); E.M. Wever (Elisabeth); G. Draisma (Gerrit); M.J. Roobol-Bouts (Monique); H.J. de Koning (Harry)

    2009-01-01

    textabstractBackground:Prostate cancer screening with prostate-specific antigen (PSA) has shown to reduce prostate cancer mortality in the European Randomised study of Screening for Prostate Cancer (ERSPC) trial. Overdetection and overtreatment are substantial unfavourable side effects with

  9. Unusual Giant Prostatic Urethral Calculus

    African Journals Online (AJOL)

    2010-06-29

    Jun 29, 2010 ... They are typically asymptomatic and may be associated with benign prostatic hyperplasia, and prostatic cancer.[1] Primary prostatic urethral calculi are usually associated with urethral strictures, posterior urethral valve or diverticula. Acute urinary retention might result secondary to a large urethral calculus.

  10. Targeting the osteosarcoma cancer stem cell

    Directory of Open Access Journals (Sweden)

    Qin Ling

    2010-10-01

    Full Text Available Abstract Osteosarcoma is the most common type of solid bone cancer and the second leading cause of cancer-related death in pediatric patients. Many patients are not cured by the current osteosarcoma therapy consisting of combination chemotherapy along with surgery and thus new treatments are urgently needed. In the last decade, cancer stem cells have been identified in many tumors such as leukemia, brain, breast, head and neck, colon, skin, pancreatic, and prostate cancers and these cells are proposed to play major roles in drug resistance, tumor recurrence, and metastasis. Recent studies have shown evidence that osteosarcoma also possesses cancer stem cells. This review summarizes the current knowledge about the osteosarcoma cancer stem cell including the methods used for its isolation, its properties, and its potential as a new target for osteosarcoma treatment.

  11. Laser prostate enucleation techniques.

    Science.gov (United States)

    Lerner, Lori B; Rajender, Archana

    2015-10-01

    Laser treatment of benign prostatic hyperplasia (BPH) through enucleation techniques has become increasingly more utilized in the field of urology. Laser enucleation of the prostate (LEP) is a transurethral procedure that employs several different types of lasers to dissect the adenoma from the surgical capsule in a retrograde fashion. We review basic laser physics and current laser prostate enucleation techniques. Holmium-LEP (HoLEP), Thulium-LEP (ThuLEP), Greenlight-LEP (GreenLEP) and Diode-LEP (DiLEP) applications are discussed. We summarize the current literature with respect to functional outcomes and complications. Although each laser device used for prostate enucleation has the same goal of removal of the adenoma from the surgical capsule, each has unique characteristics (i.e. wavelength, absorption rates) that must be understood by the practicing surgeon. Mastery of one LEP technique does not necessarily translate into facile use of an alternative enucleation energy source and/or approach. The various LEP techniques have demonstrated similar, if not superior, postoperative results to transurethral resection of the prostate (TURP), the current gold standard in the treatment of BPH. This article outlines the current LEP techniques and should serve as a quick reference for the practicing urologist.

  12. [Sexuality and prostate cancer].

    Science.gov (United States)

    Droupy, S; Al Said, B; Lechevallier, E; Colson, M-H; Giuliano, F

    2013-07-01

    All treatments for prostate cancer have a negative impact on sexuality. The objective of this review is to highlight recent developments in the management of sexual dysfunction associated with prostate cancer. We performed a literature search in the Pubmed database to select relevant articles. There is a specific profile of changes in the fields of sexual, urinary, bowel and general quality of life, according to the treatment modalities chosen. Maintenance of a satisfying sex life is a major concern of a majority of men facing prostate cancer and its treatments. It is essential to assess the couple's sexuality before treating prostate cancer in order to deliver comprehensive information and consider early therapeutic solutions adapted to the couple's expectations. The results of randomized studies show that robotic radical prostatectomy allows a faster recovery of natural erections compared to classic laparoscopy. Active pharmacological erectile rehabilitation (intracavernous injections or phosphodiesterase type 5 inhibitors [PDE5i] on demand, during the month following surgery) or passive (daily PDE5i after surgery) might improve the quality of erections especially in response to PDE5i. Unimpaired aspects of sexual response (orgasm) may, when the erection is not yet recovered, represent an alternative allowing the couple to preserve intimacy and complicity. Androgen blockade is a major barrier to maintain or return to a satisfying sex. After the treatment of prostate cancer, one specific support sometimes assisted by networking will optimize satisfying sex life recovery. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  13. Arachidonate 15-Lipoxygenase 2 as an Endogenous Inhibitor of Prostate Cancer Development

    Science.gov (United States)

    2006-03-01

    Slides were finally incubated with goat anti-rabbit IgG con- jugated to horseradish peroxidase followed by substrate (dimethyl amino azobenzene ...transformation, the results presented herein provide novel mechanistic insight on (1) the normal developmental history of prostate stem/ progenitor cells

  14. Molecular Imaging with Quantum Dots Probing EMT and Prostate Cancer Metastasis in Live Animals

    Science.gov (United States)

    2006-10-01

    marrow progenitor stem cells. Understanding the molecular mechanisms at the interface of prostate cancer and host cells could help in the future ...4139. 83. Ernst P. Review article: the role of inflammation in the pathogenesis of gastric cancer. Aliment Pharmacol Ther 1999; 13:S13-S18. 84

  15. Stem Cell Basics

    Science.gov (United States)

    ... Tips Info Center Research Topics Federal Policy Glossary Stem Cell Information General Information Clinical Trials Funding Information Current ... Basics » Stem Cell Basics I. Back to top Stem Cell Basics I. Introduction: What are stem cells, and ...

  16. Prostatic disease and sexual dysfunction.

    Science.gov (United States)

    Kim, Sae Woong

    2011-06-01

    Prostatitis and benign prostatic hyperplasia (BPH) are common prostatic diseases. Furthermore, the incidence of prostate cancer has recently shown a rapid increase, even in Korea. Pain caused by prostatitis may induce sexual dysfunction, including erectile dysfunction and ejaculatory disturbance. And BPH itself, or treatments for BPH, may affect sexual function. In addition, with increased detection of localized prostate cancer, surgical treatments and radiation therapy have also increased, and the treatments may cause sexual dysfunction. Aging is also an important factor in the deterioration of the quality of life of men. Deterioration of quality of life caused by prostate diseases may be affected not only by the prostate diseases themselves but also by the sexual dysfunction caused by the prostate diseases secondarily. Thus, consideration of these points at the time of treatment of prostate disease is required. Therapies suitable to each condition should be selected with an understanding of the close association of prostate diseases and associated sexual dysfunction with the quality of life of males.

  17. Clonogenicity: holoclones and meroclones contain stem cells.

    Directory of Open Access Journals (Sweden)

    Charlotte M Beaver

    Full Text Available When primary cultures of normal cells are cloned, three types of colony grow, called holoclones, meroclones and paraclones. These colonies are believed to be derived from stem cells, transit-amplifying cells and differentiated cells respectively. More recently, this approach has been extended to cancer cell lines. However, we observed that meroclones from the prostate cancer cell line DU145 produce holoclones, a paradoxical observation as meroclones are thought to be derived from transit-amplifying cells. The purpose of this study was to confirm this observation and determine if both holoclones and meroclones from cancer cell lines contain stem cells. We demonstrated that both holoclones and meroclones can be serially passaged indefinitely, are highly proliferative, can self-renew to form spheres, are serially tumorigenic and express stem cell markers. This study demonstrates that the major difference between holoclones and meroclones derived from a cancer cell line is the proportion of stem cells within each colony, not the presence or absence of stem cells. These findings may reflect the properties of cancer as opposed to normal cells, perhaps indicating that the hierarchy of stem cells is more extensive in cancer.

  18. Osteoporosis and prostate cancer

    DEFF Research Database (Denmark)

    Poulsen, Mads Hvid; Nielsen, Morten Frost Munk; Abrahamsen, Bo

    2014-01-01

    Abstract Objective. The aim of this study was to analyse the prevalence of osteoporosis and risk factors of osteoporotic fractures before androgen deprivation in Danish men. Treatment and prognosis of prostate cancer necessitate management of long-term consequences of androgen deprivation therapy...... (ADT), including accelerated bone loss resulting in osteoporosis. Osteoporotic fractures are associated with excess morbidity and mortality. Material and methods. Patients with prostate cancer awaiting initiation of ADT were consecutively included. Half of the patients had localized disease and were...... level was 30.5 g/l (1-5714 g/l). The average Gleason score was 7.8 (range 5-10, SD 1.1). Fifty patients had localized prostate cancer and the other 55 patients had disseminated disease. The prevalence of osteoporosis was 10% and the prevalence of osteopenia was 58% before ADT. There was no significant...

  19. Dietary tomato and lycopene impact androgen signaling- and carcinogenesis-related gene expression during early TRAMP prostate carcinogenesis

    Science.gov (United States)

    Wan, Lei; Tan, Hsueh-Li; Thomas-Ahner, Jennifer M.; Pearl, Dennis K.; Erdman, John W.; Moran, Nancy E.; Clinton, Steven K.

    2014-01-01

    Consumption of tomato products containing the carotenoid lycopene is associated with a reduced risk of prostate cancer. To identify gene expression patterns associated with early testosterone-driven prostate carcinogenesis, which are impacted by dietary tomato and lycopene, wild type (WT) and transgenic adenocarcinoma of the mouse prostate (TRAMP) mice were fed control or tomato- or lycopene-containing diets from 4-10 wk-of-age. Eight-week-old mice underwent sham surgery, castration, or castration followed by testosterone-repletion (2.5 mg/kg/d initiated 1 wk after castration). Ten-wk-old intact TRAMP mice exhibit early multifocal prostatic intraepithelial neoplasia (PIN). Of the 200 prostate cancer-related genes measured by quantitative NanoString®, 189 are detectable, 164 significantly differ by genotype, 179 by testosterone status, and 30 by diet type (Plycopene feeding (Srd5a1) and by tomato-feeding (Srd5a2, Pxn, and Srebf1). Additionally, tomato-feeding significantly reduced expression of genes associated with stem cell features, Aldh1a and Ly6a, while lycopene-feeding significantly reduced expression of neuroendocrine differentiation-related genes, Ngfr and Syp. Collectively, these studies demonstrate a profile of testosterone-regulated genes associated with early stages of prostate carcinogenesis that are potential mechanistic targets of dietary tomato components. Future studies on androgen signaling/metabolism, stem cell features, and neuroendocrine differentiation pathways may elucidate the mechanisms by which dietary tomato and lycopene impact prostate cancer risk. PMID:25315431

  20. Cabazitaxel Plus Prednisone With Octreotide For Castration-Resistant Prostate Cancer (CRPC) Previously Treated With Docetaxel

    Science.gov (United States)

    2014-11-21

    Diarrhea; Hormone-resistant Prostate Cancer; Recurrent Prostate Cancer; Stage I Prostate Cancer; Stage IIA Prostate Cancer; Stage IIB Prostate Cancer; Stage III Prostate Cancer; Stage IV Prostate Cancer

  1. Prostate specific antigen in patients of benign prostate hypertrophy and carcinoma prostate.

    Science.gov (United States)

    Malati, T; Kumari, G Rajani; Murthy, P V L N; Reddy, Ch Ram; Prakash, B Surya

    2006-03-01

    Prostate Specific Antigen (PSA) has emerged as the most applicable and important tumor marker for carcinoma prostate. In the present study PSA was determined in serum of healthy subjects, patients of benign prostate hypertrophy (BPH) and Carcinoma Prostate (Ca-P) to evaluate its diagnostic efficiency in day to day management of prostate cancer patients and in differentiating patients of early prostate cancer from those with BPH. Receiver operating characteristic curve (ROC) revealed 2 ng/ml and 10 ng/ml cut off serum PSA level for BPH and untreated carcinoma prostate patients (Ca-P). An extremely significant increase (Pprostate patients when compared to healthy males. Clinical relevance of PSA was highlighted by a case study of cancer patient prior to any therapy till death.

  2. Why STEM?

    Science.gov (United States)

    Mitts, Charles R.

    2016-01-01

    The International Technology and Engineering Educators Association (ITEEA) defines STEM as a new transdisciplinary subject in schools that integrates the disciplines of science, technology, engineering, and mathematics into a single course of study. There are three major problems with this definition: There is no consensus in support of the ITEEA…

  3. STEM Thinking!

    Science.gov (United States)

    Reeve, Edward M.

    2015-01-01

    Science, Technology, Engineering, and Mathematics (STEM) is a term seen almost daily in the news. In 2009, President Obama launched the Educate to Innovate initiative to move American students from the middle to the top of the pack in science and math achievement over the next decade (The White House, n.d.). Learning about the attributes of STEM…

  4. BTG2 Antiproliferative Gene and Prostate Cancer

    National Research Council Canada - National Science Library

    Walden, Paul D

    2008-01-01

    .... During this study we showed that BTG2 protein expression is lost as an early event in prostate carcinogenesis and that prostate cancer cells degrade BTG2 at a greater rate than noncancerous prostate cells...

  5. BTG2 Antiproliferative Gene and Prostate Cancer

    National Research Council Canada - National Science Library

    Walden, Paul D

    2007-01-01

    Levels of the BTG2 tumor suppressor protein diminish during the transition of normal prostate epithelial cells into prostate cancer cells and restoration of BTG2 expression in prostate cancer cells...

  6. Proteoglycans in prostate cancer.

    Science.gov (United States)

    Edwards, Iris J

    2012-02-21

    The complexity and diversity of proteoglycan structure means that they have a range of functions that regulate cell behavior. Through multiple interactions of their core proteins and glycosaminoglycans with extracellular matrix proteins, growth factors and chemokines, proteoglycans affect cell signaling, motility, adhesion, growth and apoptosis. Progressive changes in proteoglycans occur in the tumor microenvironment, but neither the source nor consequences of those changes are well understood. Proteoglycans studied in prostate cancer include versican--a hyalectan regulator of cell adhesion and migration-and the small leucine-rich proteoglycans decorin, biglycan and lumican, which have roles in cell signaling and tissue organization. Studies support an inhibitory role in prostate cancer for decorin and lumican. Conversely, the basement membrane proteoglycan perlecan might be a tumor promoter through upregulation of sonic hedgehog signaling. Loss of the growth-inhibitory cell-surface proteoglycans syndecan-1 and betaglycan in early prostate cancer might facilitate progression, but syndecan-1 effects are pleiotropic and its renewed expression in advanced tumors might adversely affect outcome. Importantly, cellular changes and enzymatic activity in the developing tumor can alter proteoglycan composition and structure to modify their function. Emerging studies suggest that cancers, including those of the prostate, use these changes to promote their own survival, growth, and spread.

  7. Complications of prostate biopsy

    NARCIS (Netherlands)

    Anastasiadis, Anastasios; Zapała, Lukasz; Cordeiro, Ernesto; Antoniewicz, Artur; Dimitriadis, Georgios; de Reijke, Theo

    2013-01-01

    Biopsy of the prostate is a common procedure with minor complications that are usually self-limited. However, if one considers that millions of men undergo biopsy worldwide, one realizes that although complication rate is low, the number of patients suffering from biopsy complications should not be

  8. Standards for prostate biopsy

    Science.gov (United States)

    Bjurlin, Marc A.; Taneja, Samir S.

    2014-01-01

    Purpose of review A variety techniques have emerged for optimization of prostate biopsy. In this review, we summarize and critically discuss the most recent developments regarding the optimal systematic biopsy and sampling labeling along with multiparametric MRI and MR targeted biopsies. Recent findings The use of 10–12-core extended-sampling protocols increases cancer detection rates compared to traditional sextant sampling and reduces the likelihood that patients will require a repeat biopsy, ultimately allowing more accurate risk stratification without increasing the likelihood of detecting insignificant cancers. As the number of cores increases above 12 cores, the increase in diagnostic yield becomes marginal. However, limitations of this technique include undersampling, over-sampling, and the need for repetitive biopsy. MRI and MR-targeted biopsies have demonstrated superiority over systematic biopsies for the detection of clinically significant disease and representation of disease burden, while deploying fewer cores and may have applications in men undergoing initial or repeat biopsy and those with low risk cancer on or considering active surveillance. Summary A 12-core systematic biopsy that incorporates apical and far-lateral cores in the template distribution allows maximal cancer detection, avoidance of a repeat biopsy, while minimizing the detection of insignificant prostate cancers. MRI guided prostate biopsy has an evolving role in both initial and repeat prostate biopsy strategies, as well as active surveillance, potentially improving sampling efficiency, increasing detection of clinically significant cancers, and reducing detection of insignificant cancers. PMID:24451092

  9. Comparability of prostate trials

    DEFF Research Database (Denmark)

    Suciu, S; Sylvester, R; Iversen, P

    1993-01-01

    The present overview of advanced prostate cancer required the identification of randomized clinical trials studying the question of maximal androgen blockade versus the classic castration therapy. The heterogeneity of the trials concerned the type of castration (surgical or chemical) and the type...

  10. Benign Prostatic Hyperplasia (BPH)

    Science.gov (United States)

    ... reducing enlarged prostate symptoms. But the safety and efficacy of these treatments hasn't been proved. If ... 27, 2014. Hanno PH, et al. Penn Clinical Manual of Urology. 2nd ed. ... and surgical therapies for lower urinary tract symptoms in the community ...

  11. Clinical Implications of Hedgehog Pathway Signaling in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Daniel L. Suzman

    2015-09-01

    Full Text Available Activity in the Hedgehog pathway, which regulates GLI-mediated transcription, is important in organogenesis and stem cell regulation in self-renewing organs, but is pathologically elevated in many human malignancies. Mutations leading to constitutive activation of the pathway have been implicated in medulloblastoma and basal cell carcinoma, and inhibition of the pathway has demonstrated clinical responses leading to the approval of the Smoothened inhibitor, vismodegib, for the treatment of advanced basal cell carcinoma. Aberrant Hedgehog pathway signaling has also been noted in prostate cancer with evidence suggesting that it may render prostate epithelial cells tumorigenic, drive the epithelial-to-mesenchymal transition, and contribute towards the development of castration-resistance through autocrine and paracrine signaling within the tumor microenvironment and cross-talk with the androgen pathway. In addition, there are emerging clinical data suggesting that inhibition of the Hedgehog pathway may be effective in the treatment of recurrent and metastatic prostate cancer. Here we will review these data and highlight areas of active clinical research as they relate to Hedgehog pathway inhibition in prostate cancer.

  12. Prostate ultrasound: back in business!

    Science.gov (United States)

    Crisan, Nicolae; Andras, Iulia; Radu, Corina; Andras, David; Coman, Radu-Tudor; Tucan, Paul; Pisla, Doina; Crisan, Dana; Coman, Ioan

    2017-11-29

    The use of grey scale prostate ultrasound decreased after the implementation of magnetic resonance imaging (MRI) for the diagnosis and evaluation of prostate cancer. The new developments, such as multiparametric ultrasound and MRI-ultrasound fusion technology, renewed the interest for this imaging method in the assessment of prostate cancer. The purpose of this paper was to review the current role of prostate ultrasound in the setting of these new applications. A thorough reevaluation of the selection criteria of the patients is required to assess which patients would benefit from multiparametric ultrasound, who wouldbenefit from multiparametric MRI or the combination of both to assist prostate biopsy in order to ensure the balance between overdiagnosis and underdiagnosis of prostate cancer.

  13. Prostate cancer markers: An update.

    Science.gov (United States)

    Pentyala, Srinivas; Whyard, Terry; Pentyala, Sahana; Muller, John; Pfail, John; Parmar, Sunjit; Helguero, Carlos G; Khan, Sardar

    2016-03-01

    As the most common noncutaneous malignancy in American men, prostate cancer currently accounts for 29% of all diagnosed cancers, and ranks second as the cause of cancer fatality in American men. Prostatic cancer is rarely symptomatic early in its course and therefore disease presentation often implies local extension or even metastatic disease. Thus, it is extremely critical to detect and diagnose prostate cancer in its earliest stages, often prior to the presentation of symptoms. Three of the most common techniques used to detect prostate cancer are the digital rectal exam, the transrectal ultrasound, and the use of biomarkers. This review presents an update regarding the field of prostate cancer biomarkers and comments on future biomarkers. Although there is not a lack of research in the field of prostate cancer biomarkers, the discovery of a novel biomarker that may have the advantage of being more specific and effective warrants future scientific inquiry.

  14. High Spatiotemporal Resolution Prostate MRI

    Science.gov (United States)

    2017-09-01

    AWARD NUMBER: W81XWH-15-1-0341 TITLE: High Spatiotemporal Resolution Prostate MRI PRINCIPAL INVESTIGATOR: Stephen J. Riederer, Ph.D...Resolution Prostate MRI 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1-0341 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Stephen J. Riederer E-Mail...overall purpose of this project is to develop improved means using MRI for detecting prostate cancer with the potential for differentiating disease

  15. Prostate Cancer Biorepository Network (PCBN)

    Science.gov (United States)

    2017-10-01

    Biorepository at the University of Washington joined the Prostate Cancer Pathology Resource Network (PCBN) September 30th 2014. The purpose of this...Cancer Biorepository at the University of Washington joined the Prostate Cancer Pathology Resource Network (PCBN) September 30th 2014. The UW Prostate...outcomes for the project include tissue acquisition, PDX development, and TMA construction , and specimen distribution are already discussed under

  16. Prostate Cancer Biospecimen Cohort Study

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-15-2-0062 TITLE: Prostate Cancer Biospecimen Cohort Study PRINCIPAL INVESTIGATOR: Bettina F. Drake, MPH, PhD CONTRACTING...ADDRESS. 1. REPORT DATE October 2017 2. REPORT TYPE Annual 3. DATES COVERED 30 Sep 2016 - 29 Sep 2017 4. TITLE AND SUBTITLE Prostate Cancer Biospecimen...14. ABSTRACT The goal of the study is development of a Prostate Cancer Biorepository Network (PCBN) resource site with high quality and well

  17. Prostate cancer markers: An update

    OpenAIRE

    PENTYALA, SRINIVAS; WHYARD, TERRY; PENTYALA, SAHANA; MULLER, JOHN; PFAIL, JOHN; PARMAR, SUNJIT; HELGUERO, CARLOS G.; KHAN, SARDAR

    2016-01-01

    As the most common noncutaneous malignancy in American men, prostate cancer currently accounts for 29% of all diagnosed cancers, and ranks second as the cause of cancer fatality in American men. Prostatic cancer is rarely symptomatic early in its course and therefore disease presentation often implies local extension or even metastatic disease. Thus, it is extremely critical to detect and diagnose prostate cancer in its earliest stages, often prior to the presentation of symptoms. Three of th...

  18. Hereditary aspects of prostate cancer.

    OpenAIRE

    McLellan, D. L.; Norman, R. W.

    1995-01-01

    OBJECTIVE: To review current literature on the hereditary aspects of prostate cancer and to evaluate the importance of family history in history taking and screening for prostate cancer. DATA SOURCES: MEDLINE was searched for articles in English or French published between Jan. 1, 1956, and Oct. 31, 1994, with the use of MeSH headings "prostatic neoplasms," "genetics" and "chromosomes." Additional references were selected from the bibliographies of articles found during the search. STUDY SELE...

  19. Prostate Cancer Pathology Resource Network

    Science.gov (United States)

    2015-12-01

    AD_________________ Award Number: W81XWH-10-2-0056 TITLE: Prostate Cancer Pathology Resource Network PRINCIPAL INVESTIGATOR: Bruce J. Trock, Ph.D... Pathology Resource Network 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-10-2-0056 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Bruce J. Trock, Ph.D. Betty...The Prostate Cancer Pathology Resource Network (which has since been renamed the Prostate Cancer Biorepository Network or PCBN) is a collaboration

  20. Lineage relationship of prostate cancer cell types based on gene expression

    Directory of Open Access Journals (Sweden)

    Ware Carol B

    2011-05-01

    Full Text Available Abstract Background Prostate tumor heterogeneity is a major factor in disease management. Heterogeneity could be due to multiple cancer cell types with distinct gene expression. Of clinical importance is the so-called cancer stem cell type. Cell type-specific transcriptomes are used to examine lineage relationship among cancer cell types and their expression similarity to normal cell types including stem/progenitor cells. Methods Transcriptomes were determined by Affymetrix DNA array analysis for the following cell types. Putative prostate progenitor cell populations were characterized and isolated by expression of the membrane transporter ABCG2. Stem cells were represented by embryonic stem and embryonal carcinoma cells. The cancer cell types were Gleason pattern 3 (glandular histomorphology and pattern 4 (aglandular sorted from primary tumors, cultured prostate cancer cell lines originally established from metastatic lesions, xenografts LuCaP 35 (adenocarcinoma phenotype and LuCaP 49 (neuroendocrine/small cell carcinoma grown in mice. No detectable gene expression differences were detected among serial passages of the LuCaP xenografts. Results Based on transcriptomes, the different cancer cell types could be clustered into a luminal-like grouping and a non-luminal-like (also not basal-like grouping. The non-luminal-like types showed expression more similar to that of stem/progenitor cells than the luminal-like types. However, none showed expression of stem cell genes known to maintain stemness. Conclusions Non-luminal-like types are all representatives of aggressive disease, and this could be attributed to the similarity in overall gene expression to stem and progenitor cell types.

  1. Center for Prostate Disease Research

    Science.gov (United States)

    ... and Dr. Albert Dobi, Associate Director, CPDR and Research Assistant Professor, Department of ... Autoantibodies against oncogenic ERG protein in prostate cancer: potential use in diagnosis and ...

  2. EMBOLIZATION AND CHEMOEMBOLIZATION PROSTATIC ARTERIES OF BENIGN PROSTATIC HYPERPLASIA AND PROSTATE CANCER

    Directory of Open Access Journals (Sweden)

    N. B. Tabynbaev

    2017-01-01

    Full Text Available The article gives the results of the use of embolization of prostatic arteries in benign prostatic hyperplasia in 3 patients, two of whom have been with suprapubic drainage of the bladder. The patient was 120 ml without suprapubic drainage of the bladder residual urine. The age of patients was 68 to 70 years. According TRUS, the average prostate volume was 86.0 ± 12.6 cm3 . 4 patients» superselective prostatic artery chemoembolization was performed in prostate cancer. Chemicals for carrying out this procedure served adriamycin at a dose of 50 mg. Two of the four patients with prostate cancer was hormone-resistant form. Three patients had PCa T3b N0M0 stage T2bN0M0 histologically verified number Gleason 7, 7, 8, 9. All four had difficulty urinating, the amount of residual urine was 54 to 98 ml. As a source of transportation used chemotherapy microspheres (gepasfery size of 300–500 microns. Treatment outcomes assessed at one month. The efficiency of the methods for the treatment of benign prostatic hyperplasia and prostate cancer in the form of return of spontaneous urination, decrease in residual urine, reducing the prostate-specific antigen. 

  3. New visual prostate symptom score versus international prostate ...

    African Journals Online (AJOL)

    New visual prostate symptom score versus international prostate symptom score in men with lower urinary tract symptoms: A prospective comparision in Indian rural population. ... All the patients were requested to complete the IPSS and VPSS questionnaire, and they were correlated. The urodynamic study was performed ...

  4. Predictive value of prostate-specific antigen for prostate cancer

    DEFF Research Database (Denmark)

    Shepherd, Leah; Borges, Alvaro Humberto; Ravn, Lene

    2014-01-01

    INTRODUCTION: Although prostate cancer (PCa) incidence is lower in HIV+ men than in HIV- men, the usefulness of prostate-specific antigen (PSA) screening in this population is not well defined and may have higher false negative rates than in HIV- men. We aimed to describe the kinetics and predict...

  5. The Early Prostate Cancer program: bicalutamide in nonmetastatic prostate cancer

    DEFF Research Database (Denmark)

    Iversen, Peter; Roder, Martin Andreas; Røder, Martin Andreas

    2008-01-01

    The Early Prostate Cancer program is investigating the addition of bicalutamide 150 mg to standard care for localized or locally advanced, nonmetastatic prostate cancer. The third program analysis, at 7.4 years' median follow-up, has shown that bicalutamide 150 mg does not benefit patients...

  6. Serum prostate specific antigen levels in men with benign prostatic ...

    African Journals Online (AJOL)

    Objective: To determine the sensitivity, specificity and positive predictive value of the PSA test at the conventional cut-off value of 4 ng/ml. Design: Retrospective study. Setting: Nairobi Hospital Laboratory, Nairobi. Data Source: Results of serum Prostate specific Antigen (PSA), estimation and prostate histology specimens at ...

  7. Original article The Relationship Between Prostate Volume, Prostate ...

    African Journals Online (AJOL)

    mn

    ), prostate specific antigen. (PSA) and age in a cohort of Saudi men from the Urology Department, King Abdul Aziz University. Hospital, Jeddah, Saudi Arabia. Methods: Medical records of 447 Saudi men aged 20-89 years with benign prostatic ...

  8. Functional MR Imaging in prostate radiotherapy - relationship with prostate histology

    NARCIS (Netherlands)

    Borren, A.

    2014-01-01

    The treatment of prostate cancer with radiotherapy might be improved by either increasing the radiation dose on the most important tumor areas with focal boosting or by reducing the dose on healthy prostate tissue by means of focal therapy. In both scenarios, selection of the tumor areas is a

  9. Prostatic urethral lift vs transurethral resection of the prostate

    DEFF Research Database (Denmark)

    Gratzke, Christian; Barber, Neil; Speakman, Mark J

    2017-01-01

    OBJECTIVES: To compare prostatic urethral lift (PUL) with transurethral resection of the prostate (TURP) with regard to symptoms, recovery experience, sexual function, continence, safety, quality of life, sleep and overall patient perception. PATIENTS AND METHODS: A total of 80 patients with lowe...... in statistically significant improvement in sleep. CONCLUSION: PUL was compared to TURP in a randomised, controlled study which further characterized both modalities so that care providers and patients can better understand the net benefit when selecting a treatment option.......OBJECTIVES: To compare prostatic urethral lift (PUL) with transurethral resection of the prostate (TURP) with regard to symptoms, recovery experience, sexual function, continence, safety, quality of life, sleep and overall patient perception. PATIENTS AND METHODS: A total of 80 patients with lower...... function preservation, continence preservation and safety. Additional evaluations of patient perspective, quality of life and sleep were prospectively collected, analysed and presented for the first time. RESULTS: Significant improvements in International Prostate Symptom Score (IPSS), IPSS quality of life...

  10. Characterising Castrate Tolerant Prostate Cancer Cells

    OpenAIRE

    ASHLEE KATE CLARK

    2017-01-01

    Prostate cancer is a prevalent disease in aging males. This thesis explores prostate cancer cells that escape current therapy and give rise to end-stage disease. Using sophisticated experimental approaches, this important cancer cell population was identified and characterised in human prostate cancer tissues.  Our discoveries will eventually lead to improved cancer treatments for men with prostate cancer.

  11. Chemotherapeutic prevention studies of prostate cancer

    DEFF Research Database (Denmark)

    Djavan, Bob; Zlotta, Alexandre; Schulman, Claude

    2004-01-01

    Despite advances in the detection and management of prostate cancer, this disease remains a major cause of morbidity and mortality in men. Increasing attention has focused on the role of chemoprevention for prostate cancer, ie the administration of agents that inhibit 1 or more steps in the natural...... history of prostate carcinogenesis. We review prostate cancer chemoprevention studies in Europe....

  12. Prevalence and characteristics of prostate cancer among ...

    African Journals Online (AJOL)

    abp

    Campbell L. Prevalence of elevated serum prostate-specific antigen in rural Nigeria. Int J Urol. Jun 2003; 10(6):315-. 22. PubMed | Google Scholar. 17. Rabah DM, Arafa MA. Prostate cancer screening in a Saudi population: an explanatory trial study. Prostate Cancer. Prostatic Dis. Jun 2010; 13(2):191-4. PubMed | Google.

  13. Transabdominal ultrasonographic assessment of prostate size and ...

    African Journals Online (AJOL)

    benign prostatic hyperplasia (BPH). The prostate volume has been measured by various methods including digital rectal examination, cystourethrography, urethroscopy, and urethral pressure flow ... We studied prostate dimensions and volume by transabdominal ... had enlarged prostates (range, 22.5–387 ml) with a mean.

  14. Quantify Prostate Cancer by Automated Histomorphometry

    Science.gov (United States)

    Braumann, Ulf-Dietrich; Kuska, Jens-Peer; Löffler, Markus; Wernert, Nicolas

    A new method is presented to quantify malignant changes in histological sections of prostate tissue immunohistochemically stained for prostate-specific antigen (PSA) by means of image processing. The morphological analysis of the prostate tissue uses the solidity of PSA-positive prostate tissue segments to compute a quantitative measure that turns out highly correlated with scores obtained from routine diagnosis (Gleason, Dhom).

  15. Monosodium glutamate: Potentials at inducing prostate pathologies ...

    African Journals Online (AJOL)

    The health implication of the alteration could be compounded by the opposing response elicited by increasing the concentration of either MSG or DW. Key words: Monosodium glutamate, total acid phosphatase, prostatic acid phosphatase, prostate cancer, prostatitis, benign prostate hyperplasia, infertility. African Journal of ...

  16. Prostate specific antigen in a community-based sample of men without prostate cancer: Correlations with prostate volume, age, body mass index, and symptoms of prostatism

    NARCIS (Netherlands)

    J.L.H.R. Bosch (Ruud); W.C.J. Hop (Wim); C.H. Bangma (Chris); W.J. Kirkels (Wim); F.H. Schröder (Fritz)

    1995-01-01

    textabstractThe correlation between both prostate specific antigen levels (PSA) and prostate specific antigen density (PSAD) and age, prostate volume parameters, body mass index, and the International Prostate Symptom Score (IPSS) were studied in a community‐based population. A sample of 502 men

  17. Blood lipids and prostate cancer

    DEFF Research Database (Denmark)

    Bull, Caroline J; Bonilla, Carolina; Holly, Jeff M P

    2016-01-01

    Genetic risk scores were used as unconfounded instruments for specific lipid traits (Mendelian randomization) to assess whether circulating lipids causally influence prostate cancer risk. Data from 22,249 prostate cancer cases and 22,133 controls from 22 studies within the international PRACTICAL...

  18. Genetic Analysis of Prostate Cancer

    NARCIS (Netherlands)

    D.C.J.G. van Alewijk (Dirk)

    2003-01-01

    markdownabstract__Abstract__ The human prostate has the size of a chestnut and envelops the urethra as it exits the bladder, below the bladder neck. It is the largest of the male accessory sex glands, which also include the seminal vesicles, and bulbourethral gland. The prostate is composed of

  19. Focal therapy in prostate cancer

    NARCIS (Netherlands)

    van den Bos, W.

    2016-01-01

    Interesting developments took place in the treatment of prostate cancer including focal therapy for less aggressive organ-confined prostate cancer. Fortunately, curative treatment is often still an option for patients suffering from the lower staged tumors. In carefully selected patients, the

  20. HUMAN PROSTATE CANCER RISK FACTORS

    Science.gov (United States)

    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...

  1. FastStats: Prostate Disease

    Science.gov (United States)

    ... Women’s Health State and Territorial Data Reproductive Health Contraceptive Use Infertility Reproductive Health Notice Regarding FastStats Mobile ... prostate cancer: 27,682 Deaths per 100,000 males from prostate cancer: 17.8 Source: Deaths: Final ...

  2. PROSTATE CANCER SCREENING IN GHANA -

    African Journals Online (AJOL)

    In Ghana and most African countries, prostate cancer is the most common cancer in males after hepatocellnlar carcinoma. Whereas in the advanced countries, screening for prostate specific anti- gen (PSA) has led to early detection and management of the disease, screening has been very low in Ghana, thus leading to low ...

  3. Indications for Prostatic Biopsy – which is more useful: the Prostate ...

    African Journals Online (AJOL)

    Indications for Prostatic Biopsy – which is more useful: the Prostate Specific Antigen or the Digital Rectal Examination? – An Analysis of 431 Consecutive Prostatic Biopsies at the Lagos University Teaching Hospital.

  4. The Danish Prostate Cancer Database

    DEFF Research Database (Denmark)

    Nguyen-Nielsen, Mary; Høyer, Søren; Friis, Søren

    2016-01-01

    AIM OF DATABASE: The Danish Prostate Cancer Database (DAPROCAdata) is a nationwide clinical cancer database that has prospectively collected data on patients with incident prostate cancer in Denmark since February 2010. The overall aim of the DAPROCAdata is to improve the quality of prostate cancer...... care in Denmark by systematically collecting key clinical variables for the purposes of health care monitoring, quality improvement, and research. STUDY POPULATION: All Danish patients with histologically verified prostate cancer are included in the DAPROCAdata. MAIN VARIABLES: The DAPROCAdata...... registers clinical data and selected characteristics for patients with prostate cancer at diagnosis. Data are collected from the linkage of nationwide health registries and supplemented with online registration of key clinical variables by treating physicians at urological and oncological departments. Main...

  5. Canadian prostate brachytherapy in 2012

    Science.gov (United States)

    Keyes, Mira; Crook, Juanita; Morris, W. James; Morton, Gerard; Pickles, Tom; Usmani, Nawaid; Vigneault, Eric

    2013-01-01

    Prostate brachytherapy can be used as a monotherapy for low- and intermediate-risk patients or in combination with external beam radiation therapy (EBRT) as a form of dose escalation for selected intermediate- and high-risk patients. Prostate brachytherapy with either permanent implants (low dose rate [LDR]) or temporary implants (high dose rate [HDR]) is emerging as the most effective radiation treatment for prostate cancer. Several large Canadian brachytherapy programs were established in the mid- to late-1990s. Prostate brachytherapy is offered in British Columbia, Alberta, Manitoba, Ontario, Quebec and New Brunswick. We anticipate the need for brachytherapy services in Canada will significantly increase in the near future. In this review, we summarize brachytherapy programs across Canada, contemporary eligibility criteria for the procedure, toxicity and prostate-specific antigen recurrence free survival (PRFS), as published from Canadian institutions for both LDR and HDR brachytherapy. PMID:23671495

  6. New drugs in prostate cancer

    Directory of Open Access Journals (Sweden)

    Sangjun Yoo

    2016-06-01

    Full Text Available The standard primary treatment for advanced prostate cancer has been hormonal therapy since the 1940s. However, prostate cancer inevitably progresses to castration-resistant prostate cancer (CRPC after a median duration of 18 months of androgen deprivation therapy. In patients with CRPC, docetaxel has been regarded as the standard treatment. However, survival advantages of docetaxel over other treatments are slim, and the need for new agents persists. In recent years, novel agents, including abiraterone, enzalutamide, cabazitaxel, radium-223, and sipuleucel-T, have been approved for the treatment of CRPC, and more such agents based on diverse mechanisms are under investigation or evaluation. In this article, the authors reviewed the current literature on recent advances in medical treatment of prostate cancer, especially CRPC. In addition, the authors elaborated on novel drugs for prostate cancer currently undergoing investigation and their mechanisms.

  7. Castration Induced Neuroendocrine Mediated Progression of Prostate Cancer

    Science.gov (United States)

    2008-09-01

    lineage. In other organs, the origin of NE cells has been shown to be endodermal stem cells,9,10 and a similar model was Received 14 September 2006...Leonhardt M, Janssen M, Konrad L, Bjartell A, Abrahamsson PA. Neurogenic origin of human prostate endocrine cells. Urology 1999; 53: 1041–1048. 13 Luttrell...xenograft LuCaP 23 following castration. Int J Cancer 1996; 65: 85–89. 73 Ambrosini G, Adida C, Altieri DC. A novel anti-apoptosis gene, survivin

  8. ULTRASONIC EXAMINATION OF THE BENIGN PROSTATIC HYPERTROPHY

    OpenAIRE

    棚橋, 善克

    1982-01-01

    In normal cases, prostatic section shows triangular shape and inner gland occupies a small part in only upper sections as a echogenic portion. In prostatic hypertrophy cases, inner gland occupies more part of the prostate and outer gland is shown as a half moon shape, in late stage of hypertrophy, inner gland occupies almost whole the part of the prostate, and compressed outer gland is visualized as an orange peel in postero-inferior portion. In some cases with prostatic hypertrophy, some nod...

  9. Yes-Associated Protein Expression Is Correlated to the Differentiation of Prostate Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Myung-Giun Noh

    2017-07-01

    Full Text Available Background Yes-associated protein (YAP in the Hippo signaling pathway is a growth control pathway that regulates cell proliferation and stem cell functions. Abnormal regulation of YAP was reported in human cancers including liver, lung, breast, skin, colon, and ovarian cancer. However, the function of YAP is not known in prostate adenocarcinoma. The purpose of this study was to investigate the role of YAP in tumorigenesis, differentiation, and prognosis of prostate adenocarcinoma. Methods The nuclear and cytoplasmic expression of YAP was examined in 188 cases of prostate adenocarcinoma using immunohistochemistry. YAP expression levels were evaluated in the nucleus and cytoplasm of the prostate adenocarcinoma and the adjacent normal prostate tissue. The presence of immunopositive tumor cells was evaluated and interpreted in comparison with the patients’ clinicopathologic data. Results YAP expression levels were not significantly different between normal epithelial cells and prostate adenocarcinoma. However, YAP expression level was significantly higher in carcinomas with a high Gleason grades (8–10 than in carcinomas with a low Gleason grades (6–7 (p < .01. There was no statistical correlation between YAP expression and stage, age, prostate-specific antigen level, and tumor volume. Biochemical recurrence (BCR–free survival was significantly lower in patients with high YAP expressing cancers (p = .02. However high YAP expression was not an independent prognostic factor for BCR in the Cox proportional hazards model. Conclusions The results suggested that YAP is not associated with prostate adenocarcinoma development, but it may be associated with the differentiation of the adenocarcinoma. YAP was not associated with BCR.

  10. Comparison of telomerase activity in prostate cancer, prostatic intraepithelial neoplasia and benign prostatic hyperplasia

    Directory of Open Access Journals (Sweden)

    Soleiman Mahjoub

    2006-11-01

    Full Text Available BACKGROUND: Telomerase is a reverse transcriptase enzyme that synthesizes telomeric DNA on chromosome ends. The enzyme is important for the immortalization of cancer cells because it maintains the telomeres. METHODS: Telomerase activity (TA was measured by fluorescence-based telomeric repeat amplification protocol (FTRAP assay in prostate carcinoma and benign prostatic hyperplasia (BPH. RESULTS: TA was present in 91.4% of 70 prostate cancers, 68.8% of 16 prostatic intraepithelial neoplasia (PIN, 43.3% of 30 BPH*, 21.4% of 14 atrophy and 20% of 15 normal samples adjacent to tumor. There was not any significant correlation between TA, histopathological tumor stage or gleason score. In contrast to high TA in the BPH* tissue from the cancer-bearing gland, only 6.3% of 32 BPH specimens from patients only diagnosed with BPH were telomerase activity-positive. CONCLUSIONS: These results indicate that TA is present in most prostate cancers. The high rate of TA in tissue adjacent to tumor may be attributed either to early molecular alteration of cancer that was histologically unapparent, or to the presence of occult cancer cells. Our findings suggest that the re-expression of telomerase activity could be one step in the transformation of BPH to PIN. KEY WORDS: Telomerase activity, prostate cancer, prostatic intraepithelial neoplasia, benign prostatic hyperplasia.

  11. Collection of Prostate Cancer Families and Mapping Additional Hereditary Prostate Cancer Genes (HPC2, HPC3..)

    National Research Council Canada - National Science Library

    Isaacs, William

    2001-01-01

    Segregation analyses of familial prostate cancer have provided evidence for the existence of dominantly-acting prostate cancer susceptibility alleles, with such genes being estimated to be responsible...

  12. Collection of Prostate Cancer Families and Mapping Additional Hereditary Prostate Cancer Genes (HPC2, HPC3,...)

    National Research Council Canada - National Science Library

    Isaacs, William

    2000-01-01

    Segregation analyses of familial prostate cancer have provided evidence for the existence of dominantly-acting prostate cancer susceptibility alleles, with such genes being estimated to be responsible...

  13. Prostate-specific antigen, prostate cancer, and disorders of hemostasis.

    Science.gov (United States)

    Lippi, Giuseppe; Plebani, Mario; Franchini, Massimo; Guidi, Gian Cesare; Favaloro, Emmanuel J

    2009-10-01

    Prostate cancer is the most prevalent malignancy in men and the third leading cause of cancer deaths worldwide. Disorders of hemostasis are commonplace in patients with prostate cancer and include disseminated intravascular coagulation, venous thromboembolism, acute coronary syndrome, and postsurgical bleeding. These hemostatic disorders contribute to the mortality and morbidity of prostate cancer. The leading mechanisms proposed to underlie prostate cancer-related coagulopathies are thought to be a hyperexpression of tissue factor, cancer procoagulant, and platelet-activating factor, which is then accompanied by release of large amounts of both prothrombotic and profibrinolytic substances into the bloodstream. Given the generally accepted notion that prostate-specific antigen (PSA) represents an important biomarker in prostate cancer diagnostics, large population screenings were initiated for early detection of cancer. However, recent clinical and economic drawbacks have been recently raised, including evidence that screening exposes patients to a significant risk of both overdiagnosis and overtreatment. Nevertheless, several lines of evidence suggest that PSA may have tumor-suppressing activities. Despite being a member of the vast kallikrein family, which actively interplays with the coagulation cascade, the role of PSA in the pathogenesis of hemostatic disorders observed in prostate cancer patients remains circumstantial and speculative. However, observations that the levels of this cancer marker tend to correlate positively with those of several markers of thrombin generation, and with postsurgical bleeding as well as with coronary atherosclerosis and negative outcomes of myocardial infarction, raise a new and intriguing scenario regarding the pathophysiological role of this serine protease. (c) Thieme Medical Publishers.

  14. Effects of the sesquiterpene lactone parthenolide on prostate tumor-initiating cells: an integrated molecular profiling approach

    Science.gov (United States)

    Kawasaki, Brian T.; Hurt, Elaine M.; Kalathur, Madhuri; Duhagon, Maria Ana; Milner, John A.; Kim, Young S.; Farrar, William L.

    2009-01-01

    Recent evidence suggests tumor-initating cells (TICs), also called cancer stem cells, are responsible for tumor initiation and progression; therefore, they represent an important cell population for development of future anti-cancer therapies. In this study, we show that the sesquiterpene lactone parthenolide (PTL) is cytotoxic to prostate TICs isolated from prostate cancer cell lines: DU145, PC3, VCAP and LAPC4, as well as primary prostate TICs. Furthermore, PTL inhibited TIC-driven tumor formation in mouse xenografts. Using an integrated molecular profiling approach encompassing proteomics, profiles of activated transcription factors and genomics we ascertained the effects of PTL on prostate cancer cells. In addition to the previously described effects of PTL, we determined that the non-receptor tyrosine kinase src, and many src signaling components, including: Csk, FAK, β1-arrestin, FGFR2, PKC, MEK/MAPK, CaMK, ELK-1 and ELK-1-dependent genes are novel targets of PTL action. Furthermore, PTL altered the binding of transcription factors important in prostate cancer including: C/EBP-α, fos related antigen-1 (FRA-1), HOXA-4, c-MYB, SNAIL, SP1, serum response factor (SRF), STAT3, X-box binding protein-1 (XBP1) and p53. In summary, we show PTL is cytotoxic to prostate TICs and describe the molecular events of PTL-mediated cytotoxicity. Therefore, PTL represents a promising therapeutic for prostate cancer treatment. PMID:19204913

  15. Prostate atypia: does repeat biopsy detect clinically significant prostate cancer?

    Science.gov (United States)

    Dorin, Ryan P; Wiener, Scott; Harris, Cory D; Wagner, Joseph R

    2015-05-01

    While the treatment pathway in response to benign or malignant prostate biopsies is well established, there is uncertainty regarding the risk of subsequently diagnosing prostate cancer when an initial diagnosis of prostate atypia is made. As such, we investigated the likelihood of a repeat biopsy diagnosing prostate cancer (PCa) in patients in which an initial biopsy diagnosed prostate atypia. We reviewed our prospectively maintained prostate biopsy database to identify patients who underwent a repeat prostate biopsy within one year of atypia (atypical small acinar proliferation; ASAP) diagnosis between November 1987 and March 2011. Patients with a history of PCa were excluded. Chart review identified patients who underwent radical prostatectomy (RP), radiotherapy (RT), or active surveillance (AS). For some analyses, patients were divided into two subgroups based on their date of service. Ten thousand seven hundred and twenty patients underwent 13,595 biopsies during November 1987-March 2011. Five hundred and sixty seven patients (5.3%) had ASAP on initial biopsy, and 287 (50.1%) of these patients underwent a repeat biopsy within one year. Of these, 122 (42.5%) were negative, 44 (15.3%) had atypia, 19 (6.6%) had prostatic intraepithelial neoplasia, and 102 (35.6%) contained PCa. Using modified Epstein's criteria, 27/53 (51%) patients with PCa on repeat biopsy were determined to have clinically significant tumors. 37 (36.3%) proceeded to RP, 25 (24.5%) underwent RT, and 40 (39.2%) received no immediate treatment. In patients who underwent surgery, Gleason grade on final pathology was upgraded in 11 (35.5%), and downgraded 1 (3.2%) patient. ASAP on initial biopsy was associated with a significant risk of PCa on repeat biopsy in patients who subsequently underwent definitive local therapy. Patients with ASAP should be counseled on the probability of harboring both clinically significant and insignificant prostate cancer. © 2015 Wiley Periodicals, Inc.

  16. Prostate MRI can reduce overdiagnosis and overtreatment of prostate cancer.

    Science.gov (United States)

    Rosenkrantz, Andrew B; Taneja, Samir S

    2015-08-01

    The contemporary management of prostate cancer (PCa) has been criticized as fostering overdetection and overtreatment of indolent disease. In particular, the historical inability to identify those men with an elevated PSA who truly warrant biopsy, and, for those needing biopsy, to localize aggressive tumors within the prostate, has contributed to suboptimal diagnosis and treatment strategies. This article describes how modern multi-parametric MRI of the prostate addresses such challenges and reduces both overdiagnosis and overtreatment. The central role of diffusion-weighted imaging (DWI) in contributing to MRI's current impact is described. Prostate MRI incorporating DWI achieves higher sensitivity than standard systematic biopsy for intermediate-to-high risk tumor, while having lower sensitivity for low-grade tumors that are unlikely to impact longevity. Particular applications of prostate MRI that are explored include selection of a subset of men with clinical suspicion of PCa to undergo biopsy as well as reliable confirmation of only low-risk disease in active surveillance patients. Various challenges to redefining the standard of care to incorporate solely MRI-targeted cores, without concomitant standard systematic cores, are identified. These include needs for further technical optimization of current systems for performing MRI-targeted biopsies, enhanced education and expertise in prostate MRI among radiologists, greater standardization in prostate MRI reporting across centers, and recognition of the roles of pre-biopsy MRI and MRI-targeted biopsy by payers. Ultimately, it is hoped that the medical community in the United States will embrace prostate MRI and MRI-targeted biopsy, allowing all patients with known or suspected prostate cancer to benefit from this approach. Copyright © 2015 AUR. Published by Elsevier Inc. All rights reserved.

  17. Prevalent mutations in prostate cancer.

    Science.gov (United States)

    Dong, Jin-Tang

    2006-02-15

    Quantitative and structural genetic alterations cause the development and progression of prostate cancer. A number of genes have been implicated in prostate cancer by genetic alterations and functional consequences of the genetic alterations. These include the ELAC2 (HPC2), MSR1, and RNASEL (HPC1) genes that have germline mutations in familial prostate cancer; AR, ATBF1, EPHB2 (ERK), KLF6, mitochondria DNA, p53, PTEN, and RAS that have somatic mutations in sporadic prostate cancer; AR, BRCA1, BRCA2, CHEK2 (RAD53), CYP17, CYP1B1, CYP3A4, GSTM1, GSTP1, GSTT1, PON1, SRD5A2, and VDR that have germline genetic variants associated with either hereditary and/or sporadic prostate cancer; and ANXA7 (ANX7), KLF5, NKX3-1 (NKX3.1), CDKN1B (p27), and MYC that have genomic copy number changes affecting gene function. More genes relevant to prostate cancer remain to be identified in each of these gene groups. For the genes that have been identified, most need additional genetic, functional, and/or biochemical examination. Identification and characterization of these genes will be a key step for improving the detection and treatment of prostate cancer. (c) 2005 Wiley-Liss, Inc.

  18. Relationship between prostate volume and IPSS in African men with ...

    African Journals Online (AJOL)

    Relationship between prostate volume and IPSS in African men with prostate disease. C.G. Ofoha, S.I. Shu'aibu, I.C. Akpayak, N.K Dakum, V.M. Ramyil. Abstract. Background: Most frequently encountered diseases affecting the prostate include benign prostatic hyperplasia, prostate cancer and prostatitis. Lower urinary tract ...

  19. Potency of Stem Cells

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Potency of Stem Cells. Totipotent Stem Cells (Zygote + first 2 divisions). -Can form placenta, embryo, and any cell of the body. Pluripotent (Embryonic Stem Cells). -Can form any cell of the body but can not form placenta, hence no embryo. Multipotent (Adult stem cells).

  20. A Case of Prostatic Abscess with Malignant Lymphoma Involving the Prostate

    Directory of Open Access Journals (Sweden)

    Wataru Noguchi

    2014-01-01

    Full Text Available Here, we report a case of prostatic abscess probably due to malignant lymphoma of the prostate. An 82-year-old man was referred to our hospital with chief complaints of urinary frequency and discomfort on urination. Antibiotics were prescribed, but the symptoms remained and intermittent fever appeared. The patient was diagnosed with prostatic abscess by computed tomography (CT. Digital rectal examination (DRE revealed soft prostate, and thick pus was milked out from the extrameatus by prostatic massage. For drainage, we performed transurethral resection of the prostate (TURP. Drainage by TURP was successful as CT clearly showed reduction of prostatic abscess after the operation. Nevertheless, intermittent fever did not improve and the patient’s general condition deteriorated. The day before the patient died, histopathological analysis showed prostatic abscess probably due to malignant lymphoma of the prostate and incidental adenocarcinoma. This is the first report of prostatic abscess with malignant lymphoma involving the prostate.

  1. Targeting Prostate Cancer Metastasis

    Science.gov (United States)

    2015-09-01

    achieve this goal, we cultured high-invasive prostate cancer PC3 cells and treated them with the drugs/inhibitors that were proposed to target WASF3...groups (treated by DMSO), either treated by 100 μM CYT997 or 10 μM Dasatinib suppressed the cells to spread throughout the fish body (Fig. 4). As...have scr eened t he e f fect s o f mor e t han 40 drugs on invasion using cul tur ed prost ate cancer cells and f ound t hat tar geting multiple

  2. Isolation and Characterization of Prostate Cancer Stem Cells

    Science.gov (United States)

    2013-10-01

    osteoprotegerin , a secreted receptor that functions as a RANK decoy and binds to RANKL.17,18 The ratio of RANKL to osteoprotegerin enables the remodeling...tion. Nature 390:175-179, 1997 14. Boyce BF, Xing L: Biology of RANK, RANKL, and osteoprotegerin . Arthritis Res Ther 9:S1, 2007 (suppl 1) 15...Clinical implica- tions of the osteoprotegerin /RANKL/RANK system for bone and vascular diseases. JAMA 292:490-495, 2004 18. Simonet WS, Lacey DL

  3. Isolation and Characterization of Prostate Cancer Stem Cells

    Science.gov (United States)

    2012-08-01

    similar to CD44 [30] and CD47 [50]. A truncated CD166 variant has been shown to block melanoma metastasis by interfering with the CD166-CD166 homophilic...targeting of CD47 eliminates human acute lymphoblastic leukemia. Cancer Res 71: 1374–1384. 51. Lunter PC, van Kilsdonk JW, van Beek H, Cornelissen IM

  4. Diagnostic imaging of the prostate

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Hiroki (Kyoto Prefectural Univ. of Medicine (Japan))

    1991-01-01

    Modalities for the diagnostic imaging of the prostate are surveyed. Transrectal sonography is thought to be the best method for the purpose, because of its non-invasive nature, fine picture quality, sufficient reproductivity and less expensive cost. Up-to-date utilizations of the method are described, such as diagnostic capability, staging, monitoring, screening and intervention. CT is less effective but MRI is promising to visualize internal structure inside the prostate. Two very new techniques, namely, ultrasonic Doppler color flow mapping and positron emission CT (PET), of which application to the prostate is being investigated originally in our laboratory, are introduced. (author) 100 refs.

  5. Clinical evaluation of prostatic lymphoscintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Takeuchi, Toshimi; Isogai, Kazutoshi; Yoshida, Hiroshi (Ogaki Municipal Hospital, Gifu (Japan))

    1983-09-01

    Prostatic lymphoscintigraphy using sup(99m)Technetium rhenium colloid was carried out in 15 patients with various urogenital diseases. The results in 6 cases of prostatic hypertrophy suggest that the regional lymph nodes of the prostate are the internal iliac, presacral and obturator lymph nodes. In 6 cases of postatic cancer and 2 cases of bladder cancer, visualization of these pelvic lymph nodes was frequently poor. This method is simple and safe to perform. It is considered that this method is helpful in preoperative detection of lymph nodes which can not be observed by other methods.

  6. Fish Stem Cell Cultures

    OpenAIRE

    Hong, Ni; Li, Zhendong; Hong, Yunhan

    2011-01-01

    Stem cells have the potential for self-renewal and differentiation. First stem cell cultures were derived 30 years ago from early developing mouse embryos. These are pluripotent embryonic stem (ES) cells. Efforts towards ES cell derivation have been attempted in other mammalian and non-mammalian species. Work with stem cell culture in fish started 20 years ago. Laboratory fish species, in particular zebrafish and medaka, have been the focus of research towards stem cell cultures. Medaka is th...

  7. Stem Cell Networks

    OpenAIRE

    Werner, Eric

    2016-01-01

    We present a general computational theory of stem cell networks and their developmental dynamics. Stem cell networks are special cases of developmental control networks. Our theory generates a natural classification of all possible stem cell networks based on their network architecture. Each stem cell network has a unique topology and semantics and developmental dynamics that result in distinct phenotypes. We show that the ideal growth dynamics of multicellular systems generated by stem cell ...

  8. Bone marrow macrophages support prostate cancer growth in bone.

    Science.gov (United States)

    Soki, Fabiana N; Cho, Sun Wook; Kim, Yeo Won; Jones, Jacqueline D; Park, Serk In; Koh, Amy J; Entezami, Payam; Daignault-Newton, Stephanie; Pienta, Kenneth J; Roca, Hernan; McCauley, Laurie K

    2015-11-03

    Resident macrophages in bone play important roles in bone remodeling, repair, and hematopoietic stem cell maintenance, yet their role in skeletal metastasis remains under investigated. The purpose of this study was to determine the role of macrophages in prostate cancer skeletal metastasis, using two in vivo mouse models of conditional macrophage depletion. RM-1 syngeneic tumor growth was analyzed in an inducible macrophage (CSF-1 receptor positive cells) ablation model (MAFIA mice). There was a significant reduction in tumor growth in the tibiae of macrophage-ablated mice, compared with control non-ablated mice. Similar results were observed when macrophage ablation was performed using liposome-encapsulated clodronate and human PC-3 prostate cancer cells where tumor-bearing long bones had increased numbers of tumor associated-macrophages. Although tumors were consistently smaller in macrophage-depleted mice, paradoxical results of macrophage depletion on bone were observed. Histomorphometric and micro-CT analyses demonstrated that clodronate-treated mice had increased bone volume, while MAFIA mice had reduced bone volume. These results suggest that the effect of macrophage depletion on tumor growth was independent of its effect on bone responses and that macrophages in bone may be more important to tumor growth than the bone itself. In conclusion, resident macrophages play a pivotal role in prostate cancer growth in bone.

  9. The many faces of neuroendocrine differentiation in prostate cancer progression

    Directory of Open Access Journals (Sweden)

    Stephane eTerry

    2014-03-01

    Full Text Available In normal prostate, neuroendocrine (NE cells are rare and interspersed among the epithelium. These cells are believed to provide trophic signals to epithelial cell populations through the secretion of an abundance of neuropeptides that can diffuse to influence surrounding cells. In the setting of prostate cancer (PC, NE cells can also stimulate surrounding prostate adenocarcinoma cell growth, but in some cases adenocarcinoma cells themselves acquire NE characteristics. This epithelial plasticity is associated with decreased androgen receptor (AR signaling and the accumulation of neuronal and stem cell characteristics. Transformation to a NE phenotype is one proposed mechanism of resistance to contemporary AR targeted treatments, is associated with poor prognosis, and thought to represent up to 25% of lethal PCs. Importantly, the advent of high-throughput technologies has started to provide clues for understanding the complex molecular profiles of tumors exhibiting NE differentiation. Here, we discuss these recent advances, the multifaceted manner by which a NE-like state may arise during the different stages of disease progression, and the potential benefit of this knowledge for the management of patients with advanced PC

  10. Imaging Prostatic Lipids to Distinguish Aggressive Prostate Cancer

    Science.gov (United States)

    2016-12-01

    will be those that exhibit more aggressive disease . In more aggressive cancer tissues, we expect to find metabolic signatures of enhanced fatty acid...using proton magnetic resonance spectroscopy imaging in the prediction of prostate disease aggressiveness. Mechanisms linking fatty acid synthase...design we will recruit 50 men with low- grade and 50 men with high grade prostate cancer post- diagnosis as determined prior to prostatectomy. Each

  11. Baldness, benign prostate hyperplasia, prostate cancer and androgen levels.

    Science.gov (United States)

    Faydaci, Gökhan; Bilal, Eryildirim; Necmettin, Penpegül; Fatih, Tarhan; Asuman, Orçun; Uğur, Kuyumcuoğlu

    2008-12-01

    We evaluated the pattern of baldness and serum androgen levels in patients with benign prostate hyperplasia (BPH) and prostate cancer. BPH, prostate cancer and androgenic alopecia (AA) were somehow androgen dependent and affect large population of elderly men. A total of 152 patients, 108 patients with BPH and 44 patients with prostate cancer were included in the study. We measured serum total, free and bioavailable testosterone, FSH, LH, prolactin, estradiol, albumin and SHBG levels. Baldness classification was based on Norwood's classification and we categorised baldness as vertex and frontal baldness. The frequency of AA in BPH and prostate cancer groups were not different. We looked for some correlation between the two groups with respect to AA and hormone levels. We did not find any correlation between AA and total testosterone, free testosterone, bioavailable testosterone or SHBG levels in both groups. This prospective study with selected small group of patients showed that there is no difference of male pattern baldness in BPH and prostate cancer patients and also there is no correlation between pattern of baldness and serum androgen levels.

  12. Salvage prostate cryoablation for recurrent localized prostate cancer after radiotherapy

    Directory of Open Access Journals (Sweden)

    Justin Ji-Yuen Siu

    2016-12-01

    Full Text Available Salvage prostate cryoablation (SCA for recurrent localized prostate cancer after radiotherapy has been studied in Western countries for more than a decade. We present our experience of SCA in a Taiwanese medical center. We performed four cases of SCA for recurrent localized prostate cancer after radiotherapy. The data recorded included age, cancer stage, prostate-specific antigen (PSA level, Gleason score, prostate volume and patient outcome. The median follow-up period was 17 months. All cases were biopsy-proven to have residual cancer before cryoablation. After SCA, 25% of the patients reached undetectable PSA levels, 50% showed response but did not reach undetectable levels, and 25% showed no decrease in PSA. The median recurrence-free duration after SCA was 18 months in the patients who experienced a decrease in PSA. ADT was initiated after SCA for the patient who did not show any response, and bone metastasis was later diagnosed in that patient. Most patients experienced obstructive voiding problems after SCA, which improved over time. SCA is a safe salvage option for prostate cancer patients with local recurrence after RT. The preliminary results are encouraging. More extensive imagery to exclude extra-glandular disease is warranted before SCA. A longer follow-up period and larger sample size are necessary to delineate the benefits more conclusively.

  13. Neuropilin 2: Novel Biomarker and Therapeutic Target for Aggressive Prostate Cancer

    Science.gov (United States)

    2016-11-01

    tracts and prostate lobes compared to either EHT1864 or mcr84 alone (Figures 4C and 4D). Pathological examination revealed that tumors progressed to well...Wicha, M.S., and Guan, J.L. (2009). Mammary epithelial-specific ablation of the focal adhesion kinase suppressesmammary tumorigenesis by affecting... mammary cancer stem/pro- genitor cells. Cancer Res. 69, 466–474. Man, J., Shoemake, J., Zhou, W., Fang, X., Wu, Q., Rizzo, A., Prayson, R., Bao, S., Rich

  14. Extracellular Hsp90 as a Novel Epigenetic of EMT and Metastatic Risk in Prostate Cancer

    Science.gov (United States)

    2015-12-01

    cadherin can also stimulate Wnt activation, and lead to EMT events, we also utilized CRISPR technology to downregulate E-cadherin (Task 3b). Although this...studies also suggest that eHsp90 may enhance the stem-like cell diversity existing within populations, which would be predicted to further confound...reported that secreted extracellular Hsp90 (eHsp90) initiates EMT in prostate cancer cells, coincident with its enhanced expression in mesenchymal models

  15. Methylselenium and Prostate Cancer Apoptosis

    National Research Council Canada - National Science Library

    Lu, Junxuan

    2008-01-01

    The purpose of this research is to gain a better understanding of the biochemical pathways and molecular targets for the selective induction of apoptosis signaling and execution of prostate cancer (PCa...

  16. Methylselenium and Prostate Cancer Apoptosis

    National Research Council Canada - National Science Library

    Lu, Junxuan

    2006-01-01

    The purpose of this research is to gain a better understanding of the biochemical pathways and molecular targets for the selective induction of apoptosis signaling and execution of prostate cancer (PCa...

  17. Methylselenium and Prostate Cancer Apoptosis

    National Research Council Canada - National Science Library

    Lu, Junxuan

    2007-01-01

    The purpose of this research is to gain a better understanding of the biochemical pathways and molecular targets for the selective induction of apoptosis signaling and execution of prostate cancer (PCa...

  18. ESUR prostate MR guidelines 2012

    DEFF Research Database (Denmark)

    Barentsz, Jelle O; Richenberg, Jonathan; Clements, Richard

    2012-01-01

    The aim was to develop clinical guidelines for multi-parametric MRI of the prostate by a group of prostate MRI experts from the European Society of Urogenital Radiology (ESUR), based on literature evidence and consensus expert opinion. True evidence-based guidelines could not be formulated......, but a compromise, reflected by "minimal" and "optimal" requirements has been made. The scope of these ESUR guidelines is to promulgate high quality MRI in acquisition and evaluation with the correct indications for prostate cancer across the whole of Europe and eventually outside Europe. The guidelines...... provides guidelines for magnetic resonance imaging (MRI) in prostate cancer. Clinical indications, and minimal and optimal imaging acquisition protocols are provided. A structured reporting system (PI-RADS) is described....

  19. Induced Chronic Prostatitis in Rats

    African Journals Online (AJOL)

    CNP) is the most common form of the prostatitis syndromes, approximately eight .... model group when compared with the sham group (p < 0.01). However, in PCS extract treated group, the elevation was suppressed compared with the model ...

  20. Prostatic Carcinosarcoma with Lung Metastases

    Directory of Open Access Journals (Sweden)

    Stefanie R. Furlan

    2013-01-01

    Full Text Available Carcinosarcoma of the prostate is an uncommon malignancy with poor long-term prognosis. The cancer is typically discovered at an advanced stage, and with less than 100 reported cases, there is limited literature concerning treatment options. Our patient presented with a history of benign prostatic hypertrophy, erectile dysfunction, and nocturia. Biopsy of his prostate indicated that the patient had prostatic adenocarcinoma, but histopathology after prostatectomy revealed carcinosarcoma. It has been over six years since this patient’s diagnosis of carcinosarcoma. Over this span of time, he has received a radical prostatectomy, radiotherapy, and androgen ablative therapy. The patient also developed multiple lung metastases that have been treated with video-assisted thoracic surgery and stereotactic body radiosurgery. Overall, he has remained unimpaired and in good condition despite his aggressive form of cancer.

  1. Understanding your prostate cancer risk

    Science.gov (United States)

    ... age 65 and older. Family history. Having a father, brother, or son with prostate cancer increases your ... Experts are still looking at things like diet, obesity, smoking, and other factors to see how they ...

  2. Methylselenium and Prostate Cancer Apoptosis

    National Research Council Canada - National Science Library

    Lu, Junxuan

    2005-01-01

    The purpose of this research is to gain a better understanding of the biochemical pathways and molecular targets for the selective induction of apoptosis signaling and execution of prostate cancer (PCa...

  3. Acute bacterial prostatitis with osteomyelitis

    Science.gov (United States)

    Nargund, V H; Stewart, P A Hamilton

    1995-01-01

    This short case presentation concerns the simultaneous occurrence of acute bacterial prostatitis and osteomyelitis due to staphylococcal bacteraemia hitherto unrecorded in the literature. ImagesFigure 1Figure 2 PMID:7629772

  4. Multidrug Resistance in Prostate Cancer

    NARCIS (Netherlands)

    J.P. van Brussel

    2005-01-01

    textabstractAdvanced hormone refractory prostate cancer constitutes a therapeutic challenge, because all available treatment strategies have failed to substantially increase cancer specific survival. Among these strategies, a multitude of chemotherapeutic approaches did not offer a superior life

  5. Understanding Prostate Cancer: Newly Diagnosed

    Science.gov (United States)

    ... PDF copy of the Prostate Cancer Patient Guide Spam Control Text: Please leave this field empty Understanding ... Identity Guides Receive PCF news in your inbox Spam Control Text: Please leave this field empty EIN # ...

  6. Rectal complications after prostate brachytherapy.

    Science.gov (United States)

    Shah, Shimul A; Cima, Robert R; Benoit, Eric; Breen, Elizabeth L; Bleday, Ronald

    2004-09-01

    Prostate brachytherapy is gaining wide popularity as an alternative to resection for the treatment of locally advanced prostate cancer. Rectal-urethral fistula after prostate brachytherapy is a rare but serious complication, and its incidence, presentation, risk factors, and clinical management have not been well described. From January 1997 to October 2002, seven patients with rectal-urethral fistulas were referred to two institutions (Brigham and Women's Hospital and West Roxbury Veteran's Administration Hospital) of a major teaching referral center. Clinical presentation, risk factors, prostate staging, and clinical management were examined in a retrospective fashion. Seven rectal-urethral fistulas developed from roughly 700 (1 percent) patients treated with prostate brachytherapy for prostate cancer. The average patient age was 67.7 years, preimplant prostate-specific antigen was 7.1, and Gleason score was 3+3. Symptoms occurred at a mean of 27.3 months after prostate brachytherapy was started and included anorectal pain (57 percent), clear mucous discharge (57 percent), diarrhea (43 percent), and rectal ulceration (43 percent). Coronary artery disease was a common comorbidity (71 percent). Previous transurethral resection of prostate (28 percent) and pelvic irradiation or external beam radiation therapy (14 percent) were not associated with increased risk of rectal-urethral fistula. All patients underwent a diverting colostomy (86 percent) or ileostomy (14 percent), and four patients went on to have definitive therapy. Definitive resection was performed between 5 and 43 months after diverting ostomy and was chosen on the basis of comorbid disease, quality of life, and degree of operation. Two patients required a second diversion after definitive resection because of anorectal pain and a colocutaneous fistula. Postoperative complications included myocardial infarction (14 percent), blood transfusion (14 percent), and bowel perforation (14 percent). Patients

  7. QUANTITATIVE STUDIES OF PROSTATIC SECRETION

    Science.gov (United States)

    Huggins, Charles; Clark, Philip Johnson

    1940-01-01

    Cystic hyperplasia of the prostate occurs spontaneously in senile dogs only when they possess physiologically effective amounts of androgenic hormone. The cysts are closely grouped and radially arranged in a conical manner with the base of the cone at the periphery of the gland. Flattened and columnar epithelium, varying from about 5 to 25µ are seen in each cyst. The cysts communicate with the urethra by way of ducts. Both normal and cystic prostates undergo marked atrophy when the testes are removed, the chief difference 3 months after orchiectomy being the persistence of slightly dilated clefts and spaces at the site of the former cysts in the senile state. In the castrate dog whose prostate gland is being reconstructed as result of the influence of daily injections of androgen, certain doses of estrogen prevent increase of secretion and still larger doses greatly depress the output of the gland. In dogs so treated by daily injections of testosterone propionate, 10 mg., the amount of secretion is maintained from day to day at a level by daily injections of stilbestrol, 0.4 to 0.6 mg. and greatly depressed by doses of 1 to 1.5 mg. When the larger amounts of estrogen are used, together with androgen, squamous metaplasia occurs in the posterior lobe of the prostate while the epithelium of the acini decreases in height to cuboidal or low columnar form; these histological signs of activity of both androgen and estrogen on the prostate show that inhibition of the male hormone by stilbestrol is incomplete at these ratios. In dogs with either normal or cystic prostate glands, the prostate decreases in size when estrogen is injected in amounts to depress prostatic secretion profoundly. The gland is maintained in an atrophic state and overdosage avoided by controlled periodic injections of stilbestrol until secretion is reduced to the minimum, followed by free intervals, the estrogen being again administered when secretion measurably increases. The shrinkage is related to

  8. Perceived causes of prostate cancer among prostate cancer survivors in the Netherlands

    NARCIS (Netherlands)

    Kok, D.E.G.; Cremers, R.G.H.M.; Aben, K.K.H.; Oort, van I.M.; Kampman, E.; Kiemeney, L.A.L.M.

    2013-01-01

    Introduction The aim of this study was to evaluate self-reported causes of prostate cancer among prostate cancer survivors in the Netherlands to obtain insight into the common beliefs and perceptions of risk factors for prostate cancer. Materials and methods A total of 956 prostate cancer survivors,

  9. Leukocytic promotion of prostate cellular proliferation.

    Science.gov (United States)

    McDowell, Kristy L; Begley, Lesa A; Mor-Vaknin, Nirit; Markovitz, David M; Macoska, Jill A

    2010-03-01

    Histological evidence of pervasive inflammatory infiltrate has been noted in both benign prostatic hyperplasia/hypertrophy (BPH) and prostate cancer (PCa). Cytokines known to attract particular leukocyte subsets are secreted from prostatic stroma consequent to aging and also from malignant prostate epithelium. Therefore, we hypothesized that leukocytes associated with either acute or chronic inflammation attracted to the prostate consequent to aging or tumorigenesis may promote the abnormal cellular proliferation associated with BPH and PCa. An in vitro system designed to mimic the human prostatic microenvironment incorporating prostatic stroma (primary and immortalized prostate stromal fibroblasts), epithelium (N15C6, BPH-1, LNCaP, and PC3 cells), and inflammatory infiltrate (HL-60 cells, HH, and Molt-3 T-lymphocytes) was developed. Modified Boyden chamber assays were used to test the ability of prostate stromal and epithelial cells to attract leukocytes and to test the effect of leukocytes on prostate cellular proliferation. Antibody arrays were used to identify leukocyte-secreted cytokines mediating prostate cellular proliferation. Leukocytic cells migrated towards both prostate stromal and epithelial cells. CD4+ T-lymphocytes promoted the proliferation of both transformed and non-transformed prostate epithelial cell lines tested, whereas CD8+ T-lymphocytes as well as dHL-60M macrophagic and dHL-60N neutrophilic cells selectively promoted the proliferation of PCa cells. The results of these studies show that inflammatory cells can be attracted to the prostate tissue microenvironment and can selectively promote the proliferation of non-transformed or transformed prostate epithelial cells, and are consistent with differential role(s) for inflammatory infiltrate in the etiologies of benign and malignant proliferative disease in the prostate. Prostate 70: 377-389, 2010. (c) 2009 Wiley-Liss, Inc.

  10. Efficacy and safety of photoselective vaporization of the prostate in patients with prostatic obstruction induced by advanced prostate cancer

    Directory of Open Access Journals (Sweden)

    Yuan-Tso Cheng

    2011-07-01

    Conclusions: Our preliminary results suggest that PVP is a safe and effective procedure for relieving prostatic obstruction without intraoperative blood transfusion, water intoxication, or other complications in patients with advanced prostate cancer.

  11. Neuroendorine differentiation in prostate cancer: A mechanism of radioresistance and treatment failure

    Directory of Open Access Journals (Sweden)

    Chang-Deng eHu

    2015-04-01

    Full Text Available Neuroendocrine differentiation (NED in prostate cancer is a well recognized phenotypic change by which prostate cancer cells transdifferentiate into neuroendocrine-like (NE-like cells. NE-like cells lack the expression of androgen receptor and prostate specific antigen, and are resistant to treatments. In addition, NE-like cells secrete peptide hormones and growth factors to support the growth of surrounding tumor cells in a paracrine manner. Accumulated evidence has suggested that NED is associated with disease progression and poor prognosis. The importance of NED in prostate cancer progression and therapeutic response is further supported by the fact that therapeutic agents, including androgen deprivation therapy, chemotherapeutic agents, and radiotherapy, also induce NED. We will review the work supporting the overall hypothesis that therapy-induced NED is a mechanism of resistance to treatments, as well as discuss the relationship between therapy-induced NED and therapy-induced senescence, epithelial-to-mesenchymal transition, and cancer stem cells. Furthermore, we will use radiation-induced NED as a model to explore several NED-based targeting strategies for development of novel therapeutics. Finally, we propose future studies that will specifically address therapy-induced NED in the hope that a better treatment regimen for prostate cancer can be developed.

  12. A Large Posteriorly Located Prostatic Mass Lesion Challenging the Robotic Surgeon: Prostate Leiomyoma.

    Science.gov (United States)

    Keske, Murat; Canda, Abdullah Erdem; Atmaca, Ali Fuat; Bedir, Fevzi; Gecit, Ilhan; Ardicoglu, Arslan; Aydogdu, Ozge Basaran; Agackiran, Yetkin; Ocal, Berrak Gumuskaya

    2017-01-01

    Background: Prostatic leiomyoma is a benign and rare condition of the prostate. Robotic surgery is increasingly being applied in the surgical management of prostate cancer. Case Presentation: Herein, a mass lesion that was located in the posterior part of the prostate between seminal vesicles that was identified during robotic surgery is presented. This lesion further challenged the console surgeon during performing a robotic radical prostatectomy procedure for a 200 g large prostate with prostate cancer. Conclusion: Prostatic leiomyomas that are benign mesenchymal smooth muscle tumors might present as a posteriorly located mass lesion between seminal vesicles that could challenge the surgeon during surgery, which should be kept in mind.

  13. Serum Autoantibodies in Chronic Prostate Inflammation in Prostate Cancer Patients.

    Directory of Open Access Journals (Sweden)

    Bettina Schlick

    Full Text Available Chronic inflammation is frequently observed on histological analysis of malignant and non-malignant prostate specimens. It is a suspected supporting factor for prostate diseases and their progression and a main cause of false positive PSA tests in cancer screening. We hypothesized that inflammation induces autoantibodies, which may be useful biomarkers. We aimed to identify and validate prostate inflammation associated serum autoantibodies in prostate cancer patients and evaluate the expression of corresponding autoantigens.Radical prostatectomy specimens of prostate cancer patients (N = 70 were classified into high and low inflammation groups according to the amount of tissue infiltrating lymphocytes. The corresponding pre-surgery blood serum samples were scrutinized for autoantibodies using a low-density protein array. Selected autoantigens were identified in prostate tissue and their expression pattern analyzed by immunohistochemistry and qPCR. The identified autoantibody profile was cross-checked in an independent sample set (N = 63 using the Luminex-bead protein array technology.Protein array screening identified 165 autoantibodies differentially abundant in the serum of high compared to low inflammation patients. The expression pattern of three corresponding antigens were established in benign and cancer tissue by immunohistochemistry and qPCR: SPAST (Spastin, STX18 (Syntaxin 18 and SPOP (speckle-type POZ protein. Of these, SPAST was significantly increased in prostate tissue with high inflammation. All three autoantigens were differentially expressed in primary and/or castration resistant prostate tumors when analyzed in an inflammation-independent tissue microarray. Cross-validation of the inflammation autoantibody profile on an independent sample set using a Luminex-bead protein array, retrieved 51 of the significantly discriminating autoantibodies. Three autoantibodies were significantly upregulated in both screens, MUT, RAB11B and

  14. Serum Autoantibodies in Chronic Prostate Inflammation in Prostate Cancer Patients

    Science.gov (United States)

    Schlick, Bettina; Massoner, Petra; Lueking, Angelika; Charoentong, Pornpimol; Blattner, Mirjam; Schaefer, Georg; Marquart, Klaus; Theek, Carmen; Amersdorfer, Peter; Zielinski, Dirk; Kirchner, Matthias; Trajanoski, Zlatko; Rubin, Mark A.; Müllner, Stefan; Schulz-Knappe, Peter; Klocker, Helmut

    2016-01-01

    Background Chronic inflammation is frequently observed on histological analysis of malignant and non-malignant prostate specimens. It is a suspected supporting factor for prostate diseases and their progression and a main cause of false positive PSA tests in cancer screening. We hypothesized that inflammation induces autoantibodies, which may be useful biomarkers. We aimed to identify and validate prostate inflammation associated serum autoantibodies in prostate cancer patients and evaluate the expression of corresponding autoantigens. Methods Radical prostatectomy specimens of prostate cancer patients (N = 70) were classified into high and low inflammation groups according to the amount of tissue infiltrating lymphocytes. The corresponding pre-surgery blood serum samples were scrutinized for autoantibodies using a low-density protein array. Selected autoantigens were identified in prostate tissue and their expression pattern analyzed by immunohistochemistry and qPCR. The identified autoantibody profile was cross-checked in an independent sample set (N = 63) using the Luminex-bead protein array technology. Results Protein array screening identified 165 autoantibodies differentially abundant in the serum of high compared to low inflammation patients. The expression pattern of three corresponding antigens were established in benign and cancer tissue by immunohistochemistry and qPCR: SPAST (Spastin), STX18 (Syntaxin 18) and SPOP (speckle-type POZ protein). Of these, SPAST was significantly increased in prostate tissue with high inflammation. All three autoantigens were differentially expressed in primary and/or castration resistant prostate tumors when analyzed in an inflammation-independent tissue microarray. Cross-validation of the inflammation autoantibody profile on an independent sample set using a Luminex-bead protein array, retrieved 51 of the significantly discriminating autoantibodies. Three autoantibodies were significantly upregulated in both screens, MUT

  15. Syndecan-1 (CD138) contributes to prostate cancer progression by stabilizing tumour-initiating cells.

    Science.gov (United States)

    Shimada, Keiji; Anai, Satoshi; Fujii, Tomomi; Tanaka, Nobumichi; Fujimoto, Kiyohide; Konishi, Noboru

    2013-12-01

    Increasing evidence suggests that tumour-initiating cells (TICs) contribute to the development of prostate cancer. Here, we identified syndecan-1 as a key molecule maintaining the stability of prostate cancer TICs. Holoclones harbouring the biological properties of stemness were derived from single-cell cultures of the PC3 human prostate cancer cell line. These holoclones over-expressed syndecan-1, but showed reduced expression of NADPH oxidase (NOX) and synthesis of hydrogen peroxide and oxygen radicals. Stable RNA-mediated silencing of syndecan-1 gene expression up-regulated NOX-dependent generation of reactive oxygen species and reduced the survival of holoclones in vitro. Syndecan-1 down-regulation also strongly reduced the number of CD133(+)/CD44(+) primitive cancer cells and tumour growth in vivo. Interestingly, syndecan-1 gene knockdown significantly enhanced the tumour-suppressive effects of docetaxel by inhibiting the docetaxel-induced increase in CD133(+)/CD44(+) cells in vivo. In the transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse model of prostate cancer, early intervention with a syndecan-1 inhibitor (OGT2115) or syndecan-1 RNAi reduced the incidence of adenocarcinoma and the number of c-kit(+)/CD44(+) cells in cancer foci. Finally, we found that syndecan-1 immunopositivity in prostate cancer cells was significantly associated with biochemical recurrence after radical prostatectomy. Taken together, our results show that syndecan-1 contributes to prostatic carcinogenesis by maintaining TICs and may be a target molecule for therapy. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  16. Prostatic Artery Embolization for Enlarged Prostates Due to Benign Prostatic Hyperplasia. How I Do It

    Energy Technology Data Exchange (ETDEWEB)

    Carnevale, Francisco C., E-mail: fcarnevale@uol.com.br [University of Sao Paulo Medical School, Interventional Radiology Unit (Brazil); Antunes, Alberto A., E-mail: antunesuro@uol.com.br [University of Sao Paulo Medical School, Division of Urology (Brazil)

    2013-12-15

    Prostatic artery embolization (PAE) has emerged as an alternative to surgical treatments for benign prostatic hyperplasia (BPH). Patient selection and refined technique are essential for good results. Urodynamic evaluation and magnetic resonance imaging are very important and technical limitations are related to elderly patients with tortuous and atherosclerotic vessels, anatomical variations, difficulty visualizing and catheterizing small diameter arteries feeding the prostate, and the potential risk of bladder and rectum ischemia. The use of small-diameter hydrophilic microcatheters is mandatory. Patients can be treated safely by PAE with low rates of side effects, reducing prostate volume with clinical symptoms and quality of life improvement without urinary incontinence, ejaculatory disorders, or erectile dysfunction. A multidisciplinary approach with urologists and interventional radiologists is essential to achieve better results.

  17. Prostate Cancer: Symptoms, Tests, and Treatment

    Science.gov (United States)

    ... Products For Consumers Home For Consumers Consumer Updates Prostate Cancer: Symptoms, Tests, and Treatment Share Tweet Linkedin Pin ... Linkedin Pin it Email Print Risk factors for prostate cancer include family history, age and race; but new ...

  18. Endocrine Disruption and Human Prostate Cancer

    National Research Council Canada - National Science Library

    Risbridger, Gail

    2008-01-01

    .... In order to test the concept that Vinclozolin alters human prostate development and induces disease, we used our model system to study human prostate development and maturation over 8-12 weeks...

  19. Dietary Phytoestrogens and Prostate Cancer Prevention

    National Research Council Canada - National Science Library

    Kurzer, Mindy S; Slaton, Joel

    2007-01-01

    The main objective of this project is to evaluate the effects of soy phytoestrogens on reproductive hormones and prostate tissue markers of cell proliferation and androgen action in men at high risk of prostate cancer...

  20. Identifying Early Diagnosis Markers of Prostate Cancer

    National Research Council Canada - National Science Library

    Huang, Shuang

    2004-01-01

    .... We reasoned that the success and accuracy in early diagnosis of prostate cancer may be significantly improved if a panel of prostate cancer-specific markers can be identified and used in combination...

  1. Prostate Cancer Gene Discovery Using ROMA

    National Research Council Canada - National Science Library

    Isaacs, William B

    2007-01-01

    We hypothesized that a subset of men who develop prostate cancer (PCa) do so as a result of an inherited chromosomal deletion or amplification affecting the function of one or more critical prostate cancer susceptibility genes...

  2. Some Prostate Drugs May Do Harm

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_166950.html Some Prostate Drugs May Do Harm Hormone-based meds linked ... Popular hormone-based drugs for treating an enlarged prostate could increase men's risk of type 2 diabetes, ...

  3. Prostate-specific antigen as an estimator of prostate volume in the management of patients with symptomatic benign prostatic hyperplasia

    NARCIS (Netherlands)

    Mochtar, CA; Kiemeney, LALM; van Riemsdijk, MM; Barnett, GS; Laguna, MP; Debruyne, FMJ; de la Rosette, JJMCH

    2003-01-01

    Objectives: To assess the ability of serum prostate specific antigen (PSA) to estimate prostate volume (PV) to aid in the management of patients with benign prostatic hyperplasia (BPH). Methods: From 1989 to 2002, data were collected from 2264 patients complaining of lower urinary tract symptoms

  4. Prostate-specific antigen screening and mortality from prostate cancer.

    Science.gov (United States)

    Marcella, Stephen W; Rhoads, George G; Carson, Jeffrey L; Merlino, Frances; Wilcox, Homer

    2008-03-01

    There is no available evidence from randomized trials that early detection of prostate cancer improves health outcomes, but the prostate-specific antigen (PSA) test is commonly used to screen men for prostate cancer. The objective of the study is to see if screening with PSA decreases mortality from prostate cancer. This is a case-control study using one-to-one matching on race, age, and time of availability of exposure to PSA screening. Decedents, 380, from New Jersey Vital Statistics 1997 to 2000 inclusive, 55-79 years of age at diagnosis were matched to living controls without metastatic prostate cancer. Medical records were obtained from all providers, and we abstracted information about PSA tests from 1989 to the time of diagnosis in each index case. Measurements consist of a comparison of screening (yes, no) between cases and controls. Measure of association was the odds ratio. Eligible cases were diagnosed each year from 1989 to 1999 with the median year being 1993. PSA screening was evident in 23.2-29.2% of cases and 21.8-26.1% of controls depending on the screening criteria. The unadjusted, matched odds ratio for dying of prostate cancer if ever screened was 1.09 (95% CI 0.76 to 1.60) for the most restrictive criteria and 1.19 (95% CI, 0.85 to 1.66) for the least restrictive. Adjustment for comorbidity and education level made no significant differences in these values. There were no significant interactions by age or race. PSA screening using an ever/never tabulation for tests from 1989 until 2000 did not protect New Jersey men from prostate cancer mortality.

  5. Comparability of prostate trials

    DEFF Research Database (Denmark)

    Suciu, S; Sylvester, R; Iversen, P

    1993-01-01

    The present overview of advanced prostate cancer required the identification of randomized clinical trials studying the question of maximal androgen blockade versus the classic castration therapy. The heterogeneity of the trials concerned the type of castration (surgical or chemical) and the type...... of antiandrogen (flutamide, Anandron, or cyproterone acetate) added to castration. This paper reviews the different types of heterogeneity that might exist among trials that are involved in the overview: study design, randomization procedure, treatment evaluation, statistical evaluation, and data maturity....... In order to overcome these various types of heterogeneity and to compare like with like, the treatment comparison should be stratified a posteriori by question (i.e., type of castration or type of anti-androgen studied) and by study. In this way, one may draw valid conclusions. Of course, those trials...

  6. Epidermal growth factor in the rat prostate

    DEFF Research Database (Denmark)

    Tørring, Niels; Jørgensen, P E; Poulsen, Steen Seier

    1998-01-01

    Epidermal growth factor (EGF) induces proliferation in prostate epithelial and stromal cells in primary culture. This investigation was set up to characterize the time and spatial expression of EGF in the rat prostate.......Epidermal growth factor (EGF) induces proliferation in prostate epithelial and stromal cells in primary culture. This investigation was set up to characterize the time and spatial expression of EGF in the rat prostate....

  7. Wnt Signaling in Prostate Cancer Bone Metastases

    Science.gov (United States)

    2016-11-01

    Pten, Estrous Cycle MCB - 11 THE EFFECT OF HDACI (AR-42) ON CANINE PROSTATE CANCER METASTASIS. S. Elshafae1, N. Kohart1, L... canine prostate cancer overexpressing Dkk-1 was used in this study to investigate how enhanced Wnt/JNK signaling could alter tumor growth, metastasis and...metastatic phenotype of prostate cancer. Ace-1-Dkk-1, a canine prostate cancer overexpressing human Dkk-1, previously developed in our lab was used in

  8. Targeting Discoidin Domain Receptors in Prostate Cancer

    Science.gov (United States)

    2017-08-01

    AWARD NUMBER: W81XWH-15-1-0226 TITLE: Targeting Discoidin Domain Receptors in Prostate Cancer PRINCIPAL INVESTIGATOR: Dr. Rafael Fridman...AND SUBTITLE 5a. CONTRACT NUMBER Targeting Discoidin Domain Receptors in Prostate Cancer 5b. GRANT NUMBER W81XWH-15-1-0226 5c. PROGRAM ELEMENT...response to collagen in prostate cancer . The project’s goal is to define the expression and therapeutic potential of DDRs in prostate cancer . During

  9. Neuroendocrine carcinoma of the prostate gland.

    Science.gov (United States)

    Hoof, Pamela; Tsai-Nguyen, Ginger; Paulson, Scott; Syed, Almas; Mora, Adam

    2016-01-01

    Small cell prostate carcinoma (SCPC) has a clinical course and prognosis that is markedly different from that of common adenocarcinoma of the prostate. The patient in this case presented with fever of unknown origin, dyspnea, and near spinal cord compression. He was subsequently found to have widely metastatic high-grade neuroendocrine carcinoma of prostatic origin. This case emphasizes that despite the commonality of prostate cancer, there are rare presentations of this common disease.

  10. KLK-targeted Therapies for Prostate Cancer

    OpenAIRE

    Hannu, Koistinen; Johanna, Mattsson; Ulf-H?kan, Stenman

    2014-01-01

    Alternative treatments are urgently needed for prostate cancer, especially to address the aggressive metastatic castration-resistant disease. Proteolytic enzymes are involved in cancer growth and progression. The prostate produces several proteases, the most abundant ones being two members of the kallikrein-related peptidase (KLK) family, prostate-specific antigen (PSA) and KLK2. Despite the wide use of PSA as a clinical marker, the function(s) of PSA and other KLKs in prostate cancer are poo...

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

    Science.gov (United States)

    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.

  12. Low Risk Prostate Cancer and Active Surveillance

    NARCIS (Netherlands)

    M. Bul (Meelan)

    2013-01-01

    textabstractThe first part of this thesis comprises an introduction to prostate cancer and screening (chapter 1). The European Randomized study of Screening for Prostate Cancer (ERSPC) has shown an effect of screening on prostate cancer mortality in favor of the screening population, however,

  13. Magnetic resonance imaging of the prostate

    DEFF Research Database (Denmark)

    Iversen, P; Kjaer, L; Thomsen, C

    1988-01-01

    Magnetic resonance imaging offers new possibilities in investigation of the prostate gland. Current results of imaging and tissue discrimination in the evaluation of prostatic disease are reviewed. Magnetic resonance imaging may be useful in the staging of carcinoma of the prostate....

  14. Magnetic resonance imaging of the prostate

    DEFF Research Database (Denmark)

    Iversen, P; Kjaer, L; Thomsen, C

    1987-01-01

    Magnetic resonance imaging offers new possibilities in the investigation of the prostate. The current results of imaging and tissue discrimination in the evaluation of prostatic disease are reviewed. Magnetic resonance imaging may be of value in the staging of carcinoma of the prostate....

  15. Constitutional characteristics of zones of prostate structure

    Directory of Open Access Journals (Sweden)

    Vinnik Y.Y.

    2012-06-01

    Full Text Available The research article is devoted to the study of structural characteristics of prostate according to the young men constitution. Materials and methods: 540 vertical and horizontal sections of prostate have been investigated. Results: Size characteristics of prostate have been established in men of different somatotypes

  16. MANAGEMENT AND SURVIVAL IN ADVANCED PROSTATE ...

    African Journals Online (AJOL)

    hi-tech

    2000-05-05

    May 5, 2000 ... Objective: To evaluate the management and survival of patients with advanced prostate cancer in this locality. Design: A prospective case study. Setting: Kenyatta National Referral Hospital and the Nairobi and Mater Hospitals. Patients: Fifty nine patients with advanced cancer of prostate (extra prostatic ...

  17. Prostate cancer may trigger paraneoplastic limbic encephalitis

    DEFF Research Database (Denmark)

    Jakobsen, Jakob Kristian; Zakharia, Elias Raja; Boysen, Anders Kindberg Fossø

    2013-01-01

    -Hu antibody test the patient was diagnosed with paraneoplastic limbic encephalitis related to prostate cancer. The patient died within 6 months. We review the literature on prostate cancer-related paraneoplastic limbic encephalitis. High-risk prostate cancer can trigger paraneoplastic limbic encephalitis...

  18. Improving Screening Strategies for Prostate Cancer

    NARCIS (Netherlands)

    T. Wolters (Tineke)

    2010-01-01

    textabstractTh is thesis describes research on screening for prostate cancer. To improve understanding of the thesis, some background information will be provided in this introduction. First, a short description of the prostate and of prostate cancer will be given in Chapter 1, followed by

  19. Prevalence of clinical benign prostatic hyperplasia amongst ...

    African Journals Online (AJOL)

    Objectives: To determine the prevalence of benign prostatic hyperplasia (BPH) and correlates International Prostate Symptom Score (IPSS), peak/maximum flow rate (Qmax), quality of life (QoL) score and prostate volume (PV) amongst male adults in a rural setting in Nigeria. Subjects and methods: This is a ...

  20. The Relationship between Prostate Volume and International ...

    African Journals Online (AJOL)

    OBJECTIVE: To determine the relationship between prostate volume and international prostate symptom score (IPSS) in Africans with benign prostatic hyperplasia (BPH). PATIENTS AND METHOD: This was a prospective study of 120 men aged between 45 to 85years, who were referred to the urology outpatient facility for ...

  1. [Transrectal prostate sonography in early cancer recognition].

    Science.gov (United States)

    Frentzel-Beyme, B; Aurich, B; Drakopoulos, A

    1983-12-01

    Within a mass screening program 1016 patients were investigated by transrectal ultrasound. There is generally good correlation of palpation and ultrasound diagnostic. However, prostate carcinoma was less frequently suspected by ultrasound, 2 prostate carcinomas and 1 bladder carcinoma were detected, one prostate carcinoma was missed. The value of the method is discussed.

  2. REVIEW ARTICLE: PROSTATE CANCER SCREENING USING ...

    African Journals Online (AJOL)

    FOBUR

    ABSTRACT. Background: Prostate cancer is the commonest cancer among men in Nigeria and early detection is key to cure and survival but its screening through prostate specific antigen (PSA) has remain controversial in literature. Screening with prostate specific antigen (PSA) has led to more men diagnosed with ...

  3. Practical aspects of MRI of the prostate

    Directory of Open Access Journals (Sweden)

    Dragoș Cuzino

    2014-12-01

    Full Text Available The article presents the main aspects of sectional anatomy, lymph nodes and adjacent structures as well as MRI examination standard protocol for prostate cancer diagnosis. Using MRI multiparametric examination we succeed in classifying efficiently the malignant prostatic tumors using PI- RADS system. Also, using MRI multiparametric examination we can evaluate the effectiveness of prostate cancer treatment

  4. Stem Cell Transplant

    Science.gov (United States)

    ... transplant is a procedure that infuses healthy blood stem cells into your body to replace your damaged or ... A bone marrow transplant is also called a stem cell transplant. A bone marrow transplant may be necessary ...

  5. Stem Cell Transplant

    Science.gov (United States)

    ... Graft-versus-host disease: A potential risk when stem cells come from donors If you receive a transplant ... medications and blood products into your body. Collecting stem cells for transplant If a transplant using your own ...

  6. Contact laser vaporization of the prostate for benign prostatic hypertrophy

    Science.gov (United States)

    Gomella, Leonard G.; Lotfi, M. A.; Milam, Douglas F.; Albala, David; Reagan, Gary

    1994-05-01

    The contact laser applications for the removal of the enlarged prostate are distinctly different than the majority of non-contact Nd:YAG lasers that rely on coagulation necrosis and delayed sloughing. Contact Nd:YAG laser allows cutting, coagulation and vaporization of tissue with minimal penetration beyond the contact surface. Using the contact laser prostatectomy technique, the contact laser probe directly touches and immediately vaporizes the prostatic tissue under the probe. The net result is the immediate removal of the obstructing tissue, in a manner similar to the standard electrosurgical TURP. This immediate removal of tissue offers the patient treated with the contact laser the potential for decreased catheter time and a more rapid resolution of symptoms. Our initial experience suggests that the contact technique may be better suited for the smaller prostate gland (i.e. less than 30 gm). The contact laser may also be used for a procedure termed the `laser assisted TURP': a standard electrosurgical TURP is performed and the contact laser is used for hemostasis. Several investigators have reported non-randomized results of the contact technique with good outcomes. A prospective randomized trial of the contact laser prostatectomy vrs the electrosurgical TURP is underway. The contact laser vaporization of the prostate holds great promise for the treatment of symptomatic benign prostatic hypertrophy: it is virtually bloodless and allows immediate visualization of the TUR defect.

  7. Accumulation of [{sup 11}C]acetate in normal prostate and benign prostatic hyperplasia: comparison with prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Takashi; Tsukamoto, Eriko; Takei, Toshiki; Shiga, Tohru; Nakada, Kunihiro; Tamaki, Nagara [Department of Nuclear Medicine, Hokkaido University Graduate School of Medicine, Kita 15, Nishi 6, Kita-ku, Sapporo 060-8638 (Japan); Kuge, Yuji; Katoh, Chietsugu [Department of Tracer Kinetics, Hokkaido University Graduate School of Medicine, Sapporo (Japan); Shinohara, Nobuo [Department of Nuclear Medicine, Hokkaido University Graduate School of Medicine, Sapporo (Japan)

    2002-11-01

    Carbon-11 acetate positron emission tomography (PET) has been reported to be of clinical value for the diagnosis of prostate cancer. However, no detailed analysis has yet been carried out on the physiological accumulation of [{sup 11}C]acetate in the prostate. The purpose of this study was to elucidate the physiological accumulation of [{sup 11}C]acetate in the prostate using dynamic PET. The study included 30 subjects without prostate cancer [21 with normal prostate and nine with benign prostatic hyperplasia (BPH)] and six patients with prostate cancer. A dynamic PET study was performed for 20 min after intravenous administration of 555 MBq of [{sup 11}C]acetate. The standardised uptake value (SUV) at 16-20 min post tracer administration and the early-to-late-activity ratio of the SUV (E/L ratio), which was determined by dividing the SUV{sub 6-10} {sub min} by the SUV {sub 16-20min}, were calculated to evaluate the accumulation of [ {sup 11}C]acetate. The prostate was clearly visualised and distinguished from adjacent organs in PET images in most of the cases. The SUV of the prostate (2.6 {+-}0.8) was significantly higher than that of the rectum (1.7 {+-}0.4) or bone marrow (1.3 {+-}0.3) (P <0.0001 in each case). The SUV of the normal prostate of subjects aged <50 years (3.4 {+-}0.7) was significantly higher than both the SUV for the normal prostate of subjects aged {>=}50 years (2.3 {+-}0.7) and that of subjects with BPH (2.1 {+-}0.6) (P <0.01 in each case). The primary prostate cancer in six cases was visualised by [ {sup 11}C]acetate PET. However, the difference in the SUV between subjects aged {>=}50 with normal prostate or with BPH and the patients with prostate cancer (1.9 {+-}0.6) was not statistically significant. There was also no significant difference in the E/L ratio between subjects aged {>=}50 with normal prostate (0.98 {+-}0.04) or BPH (0.96 {+-}0.08) and patients with prostate cancer (1.02 {+-}0.12). In conclusion, a normal prostate exhibits age

  8. Integrative STEM Education Defined

    OpenAIRE

    Sanders, Mark E.

    2013-01-01

    "In operationally defining integrative STEM education, we hope to avoid the gross confusion/ambiguity associated with STEM education. Those who wish to use integrative STEM education to describe instruction must be certain that instruction is grounded in the context of technological/engineering design activity.

  9. STEM Curricula. Premiere PD

    Science.gov (United States)

    Brown, Ryan, Ed.; Ernst, Jeremy, Ed.; Clark, Aaron, Ed.; DeLuca, Bill, Ed.; Kelly, Daniel, Ed.

    2017-01-01

    This professional development activity on STEM Education is designed to keep Technology and Engineering teachers up to date regarding current and important issues in the discipline. This article describes why there is a focus on STEM Education, defines STEM Education, and discusses curriculum integration and its elements.

  10. Tracking adult stem cells

    NARCIS (Netherlands)

    Snippert, H.J.G.; Clevers, H.

    2011-01-01

    The maintenance of stem-cell-driven tissue homeostasis requires a balance between the generation and loss of cell mass. Adult stem cells have a close relationship with the surrounding tissue--known as their niche--and thus, stem-cell studies should preferably be performed in a physiological context,

  11. Updates of prostate cancer staging: Prostate-specific membrane antigen

    Directory of Open Access Journals (Sweden)

    Niranjan J Sathianathen

    2016-12-01

    Full Text Available The ability to accurately stage prostate cancer in both the primary and secondary staging setting can have a major impact on management. Until recently radiological staging has relied on computer tomography, magnetic resonance imaging, and nuclear bone scans to evaluate the extent of disease. However, the utility of these imaging technologies has been limited by their sensitivity and specificity especially in detecting early recurrence. Functional imaging using positron-emission tomography with a radiolabeled ligand targeted to prostate-specific membrane antigen has transformed the prostate cancer imaging landscape. Initial results suggest that it is a substantial improvement over conventional imaging in the setting of recurrence following primary therapy by having a superior ability to detect disease and to do so at an earlier stage. Additionally, it appears that the benefits seen in the secondary staging setting may also exist in the primary staging setting.

  12. Emerging drugs for prostate cancer.

    Science.gov (United States)

    Chung, Paul H; Gayed, Bishoy A; Thoreson, Gregory R; Raj, Ganesh V

    2013-12-01

    Androgen deprivation therapy is the mainstay treatment for patients with prostate cancer who are not candidates for definitive treatment, are diagnosed with advanced disease on initial presentation or progress after primary treatment. Patients who stop responding to androgen deprivation therapy develop castration resistant prostate cancer (CRPC). Emerging drugs undergoing clinical evaluation and drugs that have recently received FDA approval for the treatment of CRPC are reviewed. As the natural history and signaling pathways of prostate cancer are better understood, new treatments and targeted therapies will be developed. The FDA recently approved 5 medications that increase survival in patients with CRPC. Additional medications and drug classes are being explored that may eventually lead to new treatment options. Articles were identified using a PubMed database search. Recent FDA medication approvals and the development of emerging treatments are promising for the future of patients with prostate cancer. The addition of new medications challenges physicians to identify the optimal sequence and/or combination in which newer and older medications should be administered. Physicians treating patients with prostate cancer have a growing responsibility to keep pace with these new medications so that they may counsel and treat patients appropriately.

  13. The histologic pattern of prostate specimens in Lagos State ...

    African Journals Online (AJOL)

    Background: Prostate carcinoma (PCA) is one of the most common causes of cancer death in men. Prostate glands have three major pathologic diseases which includes prostatitis, benign prostatic hyperplasia and carcinoma. The aim of this study is to determine the hospital prevalence of the prostate gland diseases and to ...

  14. Early results of transurethral vaporisation of prostate in Nigeria ...

    African Journals Online (AJOL)

    Objective: to determine the effectiveness of transurethral electrovaporisation of prostate for the relief of obstructive prostatic disease in Nigeria. Methods: Consecutive patients presenting with obstructive prostatic disease with prostate size of less than 40gm were treated by transurethral electrovaporisation of prostate using a ...

  15. Transrectal ultrasound-guided biopsy of the prostate: Histological ...

    African Journals Online (AJOL)

    Transrectal ultrasound-guided biopsy of the prostate: Histological pattern of prostatic diseases seen in Sokoto Northwest Nigeria. ... Thirty subjects had prostatitis associated with their histological diagnosis (28 subjects with BPH, 2 subjects with cancer of the prostate), while 2 patients had schistosomiasis of the prostate with ...

  16. Early human prostate adenocarcinomas harbor androgen-independent cancer cells.

    Directory of Open Access Journals (Sweden)

    Rita R Fiñones

    Full Text Available Although blockade of androgen receptor (AR signaling represents the main treatment for advanced prostate cancer (PrCa, many patients progress to a lethal phenotype of "Castration-Resistant" prostate cancer (CR-PrCa. With the hypothesis that early PrCa may harbor a population of androgen-unresponsive cancer cells as precursors to CR-recurrent disease, we undertook the propagation of androgen-independent cells from PrCa-prostatectomy samples of early, localized (Stage-I cases. A collection of 120 surgical specimens from prostatectomy cases was established, among which 54 were adenocarcinomas. Hormone-free cell culture conditions were developed allowing routine propagation of cells expressing prostate basal cell markers and stem/progenitor cell markers, and which proliferated as spheres/spheroids in suspension cultures. Colonies of androgen-independent epithelial cells grew out from 30/43 (70% of the adenocarcinoma cases studied in detail. Fluorescence microscopy and flow cytometry showed that CR-PrCa cells were positive for CD44, CD133, CK5/14, c-kit, integrin α2β1, SSEA4, E-Cadherin and Aldehyde Dehydrogenase (ALDH. All 30 CR-PrCa cell cultures were also TERT-positive, but negative for TMPRSS2-ERG. Additionally, a subset of 22 of these CR-PrCa cell cultures was examined by orthotopic xenografting in intact and castrated SCID mice, generating histologically typical locally-invasive human PrCa or undifferentiated cancers, respectively, in 6-8 weeks. Cultured PrCa cells and orthotopically-induced in vivo cancers lacked PSA expression. We report here the propagation of Cancer Initiating Cells (CIC directly from Stage I human PrCa tissue without selection or genetic manipulation. The propagation of stem/progenitor-like CR-PrCa cells derived from early human prostate carcinomas suggests the existence of a subpopulation of cells resistant to androgen-deprivation therapy and which may drive the subsequent emergence of disseminated CR-PrCa.

  17. Mediterranean diet adherence and prostate cancer risk.

    Science.gov (United States)

    López-Guarnido, Olga; Álvarez-Cubero, María Jesus; Saiz, Maria; Lozano, David; Rodrigo, Lourdes; Pascual, Manrique; Cozar, Jose Manuel; Rivas, Ana

    2014-10-31

    Countries following the traditional Mediterranean Diet, particularly Southern European countries, have lower prostate cancer incidence and mortality compared to other European regions. The beneficial effect has been attributed to a specific eating pattern. The purpose of this review is to examine the evidence to date on the effects of adherence to a Mediterranean Diet on prostate cancer risk; and to identify which elements of the Mediterranean diet are likely to protect against prostate cancer. The search for articles came from extensive research in the following databases: PubMed, Scopus and Web of Science. We used the search terms "Mediterranean diet", "adherence", "fruit and vegetable", "olive oil", "fish" "legume", "cereal" "alcohol" "milk", "dairy product","prostate cancer", and combinations, such as "Mediterranean diet and prostate cancer" or "Olive oil and prostate cancer". There is strong evidence supporting associations between foods that are typical of a Mediterranean eating pattern and reduced prostate cancer risk. However, there are few studies that have assessed the effect of the Mediterranean diet on cancer prostate incidence. Recent data do not support associations to adherence to a Mediterranean Diet and risk of prostate cancer or disease progression. However, Mediterranean eating pattern after diagnosis of nonmetastatatic cancer was associated with lower overall mortality. Further large-scale studies are required to clarify the effect of Mediterranean diet on prostate health, in order to establish the role of this diet in the prevention of prostate cancer. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  18. Saw palmetto for prostate disorders.

    Science.gov (United States)

    Gordon, Andrea E; Shaughnessy, Allen F

    2003-03-15

    Saw palmetto is an herbal product used in the treatment of symptoms related to benign prostatic hyperplasia. The active component is found in the fruit of the American dwarf palm tree. Studies have demonstrated the effectiveness of saw palmetto in reducing symptoms associated with benign prostatic hyperplasia. Saw palmetto appears to have efficacy similar to that of medications like finasteride, but it is better tolerated and less expensive. There are no known drug interactions with saw palmetto, and reported side effects are minor and rare. No data on its long-term usage are available. The herbal product also has been used to treat chronic prostatitis, but currently there is no evidence of its efficacy.

  19. Metastatic Prostate Cancer of Hand

    Directory of Open Access Journals (Sweden)

    Akihito Nagano

    2016-01-01

    Full Text Available Soft tissue metastases of prostate cancer to other sites are extremely rare, and, to our best knowledge, there have been no reports of metastasis to soft tissue of the hand. A 63-year-old man was diagnosed with prostatic cancer. During treatment, bone and soft tissue metastases to the right hand, appearing in the first web space, were observed. The tumor was resected, along with both the first and second metacarpal bones. The thumb was reconstructed by pollicization of the remaining index finger, enabling the patient to use the pollicized thumb for activities of daily living. This is the first case report of prostate cancer metastasizing to the soft tissue in hand. After wide resection, pollicization was able to reconstruct a functional hand and thumb.

  20. Screening spectroscopy of prostate cancer

    Science.gov (United States)

    Yermolenko, S. B.; Voloshynskyy, D. I.; Fedoruk, O. S.

    2015-11-01

    The aim of the study was to establish objective parameters of the field of laser and incoherent radiation of different spectral ranges (UV, visible, IR) as a non-invasive optical method of interaction with different samples of biological tissues and fluids of patients to determine the state of prostate cancer and choosing the best personal treatment. The objects of study were selected venous blood plasma of patient with prostate cancer, histological sections of rat prostate gland in the postoperative period. As diagnostic methods have been used ultraviolet spectrometry samples of blood plasma in the liquid state, infrared spectroscopy middle range (2,5-25 microns) dry residue of plasma by spectral diagnostic technique of thin histological sections of biological tissues.

  1. Plant stem cell niches.

    Science.gov (United States)

    Aichinger, Ernst; Kornet, Noortje; Friedrich, Thomas; Laux, Thomas

    2012-01-01

    Multicellular organisms possess pluripotent stem cells to form new organs, replenish the daily loss of cells, or regenerate organs after injury. Stem cells are maintained in specific environments, the stem cell niches, that provide signals to block differentiation. In plants, stem cell niches are situated in the shoot, root, and vascular meristems-self-perpetuating units of organ formation. Plants' lifelong activity-which, as in the case of trees, can extend over more than a thousand years-requires that a robust regulatory network keep the balance between pluripotent stem cells and differentiating descendants. In this review, we focus on current models in plant stem cell research elaborated during the past two decades, mainly in the model plant Arabidopsis thaliana. We address the roles of mobile signals on transcriptional modules involved in balancing cell fates. In addition, we discuss shared features of and differences between the distinct stem cell niches of Arabidopsis.

  2. Proton MR spectroscopy of the prostate

    Energy Technology Data Exchange (ETDEWEB)

    Mueller-Lisse, Ullrich G. [Dept. of Clinical Radiology, Klinikum der Universitaet Muenchen, Standorte Grosshadern und Innenstadt, Ziemssenstrasse 1, D-80336 Munich (Germany)], E-mail: ullrich.mueller-lisse@med.uni-muenchen.de; Scherr, Michael K. [Dept. of Clinical Radiology, Klinikum der Universitaet Muenchen, Standorte Grosshadern und Innenstadt, Ziemssenstrasse 1, D-80336 Munich (Germany)

    2007-09-15

    Purpose: To summarize current technical and biochemical aspects and clinical applications of proton magnetic resonance spectroscopy (MRS) of the human prostate in vivo. Material and methods: Pertinent radiological and biochemical literature was searched and retrieved via electronic media (medline, pubmed). Basic concepts of MRS of the prostate and its clinical applications were extracted. Results: Clinical MRS is usually based on point resolved spectroscopy (PRESS) or spin echo (SE) sequences, along with outer volume suppression of signals from outside of the prostate. MRS of the prostate detects indicator lines of citrate, choline, and creatine. While healthy prostate tissue demonstrates high levels of citrate and low levels of choline that marks cell wall turnover, prostate cancer utilizes citrate for energy metabolism and shows high levels of choline. The ratio of (choline + creatine)/citrate distinguishes between healthy tissue and prostate cancer. Particularly when combined with magnetic resonance (MR) imaging, three-dimensional MRS imaging (3D-CSI, or 3D-MRSI) detects and localizes prostate cancer in the entire prostate with high sensitivity and specificity. Combined MR imaging and 3D-MRSI exceed the sensitivity and specificity of sextant biopsy of the prostate. When MRS and MR imaging agree on prostate cancer presence, the positive predictive value is about 80-90%. Distinction between healthy tissue and prostate cancer principally is maintained after various therapeutic treatments, including hormone ablation therapy, radiation therapy, and cryotherapy of the prostate. Conclusions: Since it is non-invasive, reliable, radiation-free, and essentially repeatable, combined MR imaging and 3D-MRSI of the prostate lends itself to the planning of biopsy and therapy, and to post-therapeutic follow-up. For broad clinical acceptance, it will be necessary to facilitate MRS examinations and their evaluation and make MRS available to a wider range of institutions.

  3. Epigenetics of prostate cancer.

    Science.gov (United States)

    McKee, Tawnya C; Tricoli, James V

    2015-01-01

    The introduction of novel technologies that can be applied to the investigation of the molecular underpinnings of human cancer has allowed for new insights into the mechanisms associated with tumor development and progression. They have also advanced the diagnosis, prognosis and treatment of cancer. These technologies include microarray and other analysis methods for the generation of large-scale gene expression data on both mRNA and miRNA, next-generation DNA sequencing technologies utilizing a number of platforms to perform whole genome, whole exome, or targeted DNA sequencing to determine somatic mutational differences and gene rearrangements, and a variety of proteomic analysis platforms including liquid chromatography/mass spectrometry (LC/MS) analysis to survey alterations in protein profiles in tumors. One other important advancement has been our current ability to survey the methylome of human tumors in a comprehensive fashion through the use of sequence-based and array-based methylation analysis (Bock et al., Nat Biotechnol 28:1106-1114, 2010; Harris et al., Nat Biotechnol 28:1097-1105, 2010). The focus of this chapter is to present and discuss the evidence for key genes involved in prostate tumor development, progression, or resistance to therapy that are regulated by methylation-induced silencing.

  4. Nebraska Prostate Cancer Research Program

    Science.gov (United States)

    2015-10-01

    S.A. (2008). Androgen-independent prostate cancer cells acquire the complete steroidogenic potential of synthesizing testosterone from cholesterol...Prostate  Cancer Metastasis J. Mott  UNMC  MicroRNA in growth regulation and  therapy  E. Rogan UNMC Metabolism  of Dietary and  Environmental Chemicals...nitrocellulose membrane. β‐actin is used for normalization of  samples  • Quantitative  real‐time PCR analysis of alcohol  metabolizing  enzymes:  mRNAs of

  5. The prostate health index selectively identifies clinically significant prostate cancer

    NARCIS (Netherlands)

    S. Loeb (Stacy); M.G. Sanda (Martin G.); D.L. Broyles (Dennis L.); S.S. Shin (Sanghyuk S.); C.H. Bangma (Chris); J.T. Wei (John T.); A.W. Partin (Alan W.); G.G. Klee (George); K.M. Slawin (Kevin M.); L.S. Marks (Leonard S.); R.H.N. van Schaik (Ron); D.W. Chan (Daniel); L. Sokoll (Lori); A.B. Cruz (Amabelle B.); I.A. Mizrahi (Isaac A.); W.J. Catalona (William)

    2015-01-01

    textabstractPurpose The Prostate Health Index (phi) is a new test combining total, free and [-2]proPSA into a single score. It was recently approved by the FDA and is now commercially available in the U.S., Europe and Australia. We investigate whether phi improves specificity for detecting

  6. Prostate Cancer Screening: Should You Get a PSA Test?

    Science.gov (United States)

    ... PSA test result turns out to have prostate cancer. Some prostate cancers, particularly those that grow quickly, may not ... and prevention. Cancer.Net. http://www.cancer.net/cancer-types/prostate-cancer/risk-factors-and-prevention. Accessed Aug. 2, ...

  7. Dr. Ziya Kirkali: Managing BPH (Benign Prostatic Hyperplasia)

    Science.gov (United States)

    ... page please turn JavaScript on. Feature: Prostate Enlargement Dr. Ziya Kirkali: Managing BPH Past Issues / Winter 2017 ... Articles Treating the Problem Prostate / Understanding Prostate Enlargement / Dr. Ziya Kirkali: Managing BPH Winter 2017 Issue: Volume ...

  8. Investigating Preservice STEM Teacher Conceptions of STEM Education

    Science.gov (United States)

    Radloff, Jeff; Guzey, Selcen

    2016-01-01

    Surrounding the national emphasis on improving STEM education, effective STEM educators are required. Connected, yet often overlooked, is the need for effective preservice STEM teaching instruction for incoming educators. At a basic level, preservice STEM teacher education should include STEM content, pedagogy, and conceptualization. However, the…

  9. Malakoplakia of the Prostate as a Mimicker of Prostate Cancer on Prostate Health Index and Magnetic Resonance Imaging-Fusion Prostate Biopsy: A Case Report.

    Science.gov (United States)

    Heah, Nathaniel H; Tan, Teck Wei; Tan, Yung Khan

    2017-01-01

    Background: Isolated malakoplakia of the prostate is a rare inflammatory condition that has been clinically mistaken for prostatic malignancies. The development of Prostate Imaging Reporting and Data System (PI-RADS) classifications, and Prostate Health Index (PHI) has led to more accurate diagnosis of clinically significant disease and stratification of patients that may be at risk of prostate cancer. Case Presentation: We present a case of a 75-year-old male who was on follow-up with our hospital for elevated prostate specific antigen (PSA). He was admitted for an episode of urosepsis, which was treated with antibiotics and subsequently underwent further workup and was found to have a raised PHI, as well as a high PI-RADS classification and was later found to have malakoplakia based on histology of prostate tissue obtained during targeted magnetic resonance imaging (MRI)-guided fusion prostate biopsy. Conclusion: To our understanding, this is the first case where a prostate lesion has been labeled as a PI-RADS 5 lesion, with elevated PHI that has subsequently been proven histologically to be malakoplakia. An important possible confounder is the interval between the MRI and the episode of urosepsis and it is well known that urosepsis can affect the PSA and MRI result. We present this case to highlight the potential for a false diagnosis of prostate cancer, in spite of laboratory and radiological findings.

  10. Targeting cancer stem cells in solid tumors by vitamin D.

    Science.gov (United States)

    So, Jae Young; Suh, Nanjoo

    2015-04-01

    Cancer stem cells (CSCs) are a small subset of cells that may be responsible for initiation, progression, and recurrence of tumors. Recent studies have demonstrated that CSCs are highly tumorigenic and resistant to conventional chemotherapies, making them a promising target for the development of preventive/therapeutic agents. A single or combination of various markers, such as CD44, EpCAM, CD49f, CD133, CXCR4, ALDH-1, and CD24, were utilized to isolate CSCs from various types of human cancers. Notch, Hedgehog, Wnt, and TGF-β signalingregulate self-renewal and differentiation of normal stem cells andare aberrantly activated in CSCs. In addition, many studies have demonstrated that these stem cell-associated signaling pathways are required for the maintenance of CSCs in different malignancies, including breast, colorectal, prostate, and pancreatic cancers. Accumulating evidence has shown inhibitory effects of vitamin D and its analogs on the cancer stem cell signaling pathways, suggesting vitamin D as a potential preventive/therapeutic agent against CSCs. In this review, we summarize recent findings about the roles of Notch, Hedgehog, Wnt, and TGF-β signaling in CSCs as well as the effects of vitamin D on these stem cell signaling pathways. This article is part of a Special Issue entitled '17th Vitamin D Workshop'. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Testosterone Regulates Tight Junction Proteins and Influences Prostatic Autoimmune Responses

    OpenAIRE

    Meng, Jing; Mostaghel, Elahe A.; Vakar-Lopez, Funda; Montgomery, Bruce; True, Larry; Nelson, Peter S.

    2011-01-01

    Testosterone and inflammation have been linked to the development of common age-associated diseases affecting the prostate gland including prostate cancer, prostatitis, and benign prostatic hypertrophy. We hypothesized that testosterone regulates components of prostate tight junctions which serve as a barrier to inflammation, thus providing a connection between age- and treatment-associated testosterone declines and prostatic pathology. We examined the expression and distribution of tight jun...

  12. Influence of prostate size on the outcome of holmium laser enucleation of the prostate.

    Science.gov (United States)

    Shah, Hemendra N; Sodha, Hiren S; Kharodawala, Shabbir J; Khandkar, Amit A; Hegde, Sunil S; Bansal, Manish B

    2008-06-01

    To analyse the effect of prostate size on the outcome of holmium laser enucleation of prostate (HoLEP, an established procedure for treating symptomatic benign prostatic hypertrophy, BPH), in the initial 354 patients at 1 year of follow-up. We retrospectively reviewed the records of 354 patients who had HoLEP at our institution from April 2003 to March 2007. In 235 patients the prostate weighed 100 g (group 3). Demographic data and perioperative variables were recorded and compared among the three groups. The mean prostate size was 38.1, 76.4 and 133.5 g for groups 1, 2 and 3, respectively (P prostate was 18.47, 40.8 and 82.76 g, respectively (P prostate size, and is associated with low morbidity. The efficiency of HoLEP increases with increasing prostate size.

  13. Prostate-specific antigen: does the current evidence support its use in prostate cancer screening?

    LENUS (Irish Health Repository)

    Duffy, Michael J

    2012-02-01

    Although widely used, the value of prostate-specific antigen (PSA) in screening asymptomatic men for prostate cancer is controversial. Reasons for the controversy relate to PSA being less than an ideal marker in detecting early prostate cancer, the possibility that screening for prostate cancer may result in the overdetection and thus overtreatment of indolent disease and the lack of clarity as to the definitive or best treatment for men diagnosed with localized prostate cancer. Although the results from some randomized prospective trials suggest that screening with PSA reduces mortality from prostate cancer, the overall benefit was modest. It is thus currently unclear as to whether the modest benefit of reduced mortality outweighs the harms of overdetection and overtreatment. Thus, prior to undergoing screening for prostate cancer, men should be informed of the risks and benefits of early detection. Newly emerging markers that may complement PSA in the early detection of prostate cancer include specific isoforms of PSA and PCA3.

  14. Can microfocal prostate cancer be regarded as low-risk prostate cancer?

    Directory of Open Access Journals (Sweden)

    Seung Hwan Lee

    2013-12-01

    Conclusions: Based on higher rates of Gleason score upgrading or stage upgrading cases in microfocal prostate cancer group, compared with nonmicrofocal prostate cancer group, active surveillance should be cautiously applied to these patients.

  15. Identification of Different Classes of Luminal Progenitor Cells within Prostate Tumors

    Directory of Open Access Journals (Sweden)

    Supreet Agarwal

    2015-12-01

    Full Text Available Primary prostate cancer almost always has a luminal phenotype. However, little is known about the stem/progenitor properties of transformed cells within tumors. Using the aggressive Pten/Tp53-null mouse model of prostate cancer, we show that two classes of luminal progenitors exist within a tumor. Not only did tumors contain previously described multipotent progenitors, but also a major population of committed luminal progenitors. Luminal cells, sorted directly from tumors or grown as organoids, initiated tumors of adenocarcinoma or multilineage histological phenotypes, which is consistent with luminal and multipotent differentiation potentials, respectively. Moreover, using organoids we show that the ability of luminal-committed progenitors to self-renew is a tumor-specific property, absent in benign luminal cells. Finally, a significant fraction of luminal progenitors survived in vivo castration. In all, these data reveal two luminal tumor populations with different stem/progenitor cell capacities, providing insight into prostate cancer cells that initiate tumors and can influence treatment response.

  16. Biomarkers of Prostatic Cancer: An Attempt to Categorize Patients into Prostatic Carcinoma, Benign Prostatic Hyperplasia, or Prostatitis Based on Serum Prostate Specific Antigen, Prostatic Acid Phosphatase, Calcium, and Phosphorus

    Directory of Open Access Journals (Sweden)

    Shahana Sarwar

    2017-01-01

    Full Text Available Prostatitis, BPH, and P.Ca are the most frequent pathologies of the prostate gland that are responsible for morbidity in men. Raised levels of PSA are seen in different pathological conditions involving the prostate. PAP levels are altered in inflammatory or infectious or abnormal growth of the prostate tissue. Serum calcium and phosphorus levels were also found to be altered in prostate cancer and BPH. The present study was carried out to study the levels of PSA, PAP, calcium, and phosphorus in serum of patients with Prostatitis, BPH, or P.Ca and also to evaluate the relationship between them. Males in the age group of 50–85 years with LUTS disease symptoms and with PSA levels more than 4 ng/mL were included. A total of 114 patients were analyzed including 30 controls. Prostatitis in 35.7% of cases, BPH in 35.7% of the cases, and P.Ca in 28.57% of the cases were observed. Thus, the nonmalignant cases constitute a majority. PSA, a marker specific for prostatic conditions, was significantly high in all the diseases compared to controls. A rise in serum PSA and PAP indicates prostatitis or, in combination with these two tests, decreased serum calcium shows advanced disease.

  17. Prostate Cancer Pathology Resource Network

    Science.gov (United States)

    2013-07-01

    PCBN is a public bioresource that provides tissue and other biospecimens to all prostate cancer investigators through an application process (http...number (RIN) was assessed by 2100 bioanalyzer (Agilent Technologies ). Additional information regarding PCBN SOPs for DNA and RNA extraction can be found

  18. Prostate Cancer Screening - Multiple Languages

    Science.gov (United States)

    ... Polish (polski) Portuguese (português) Russian (Русский) Spanish (español) Urdu (اردو) Vietnamese (Tiếng Việt) HealthReach resources will open ... Cancer Screening - español (Spanish) PDF American Cancer Society Urdu (اردو) Expand Section It's No Big Deal - Prostate ...

  19. [Importance of repeat laterally directed sextant prostate biopsy for detection of prostate cancer in high-risk patients].

    Science.gov (United States)

    Vaiciūnas, Kestutis; Auskalnis, Stasys; Matjosaitis, Aivaras; Mickevicius, Antanas; Mickevicius, Ramūnas; Trumbeckas, Darius; Jievaltas, Mindaugas

    2007-01-01

    Our purpose was to evaluate the relevance of repeat laterally directed sextant prostate biopsy for detection of prostate cancer in high-risk patients. Our study included 195 men at high risk for prostate cancer (elevated prostate-specific antigen level and/or abnormal prostate detected by digital rectal examination). We consulted the patients in outpatient department of Kaunas University of Medicine Hospital during 2003-2007. We performed transrectal ultrasound-guided laterally directed sextant prostate biopsy in every patient. For the patients with benign histological findings and increased risk of prostate cancer, laterally directed sextant biopsies were repeated. Prostate cancer was detected in 30.3% of patients (59/195) on the first prostate biopsy, in 13.1% (11/84) on the second prostate biopsy, in 10.3% (4/39) on the third, and in 7.7% (1/13) on the forth biopsy. After all biopsies, prostate cancer was detected in 38.5% (75/195) of patients, and it differed significantly from the percentage of prostate cancer cases detected on the first biopsy (30.3%, P=0.04). We detected 78.7% (59/75) of all prostate cancer cases by the first laterally directed sextant prostate biopsy. The rest 21.3% (16/75) of cases we detected by repeat biopsies. The second laterally directed sextant prostate biopsy revealed additional 14.6% (n=11) of prostate cancer cases and increased the detection of prostate cancer to 93.3% (70/75). At the time of the first prostate biopsy, prostate cancer was diagnosed most frequently when patients had both risk factors: elevated prostate-specific antigen level and abnormal digital prostate examination; prostate cancer was diagnosed in 45.3% of these patients. The odds ratio to detect prostate cancer by the first biopsy in patients with elevated prostate-specific antigen level and abnormal digital prostate examination was 3.7, and odds ratio to detect prostate cancer by repeat biopsies was 4.7. Repeat ultrasound-guided laterally directed sextant

  20. Global Collaborative STEM Education

    Science.gov (United States)

    Meabh Kelly, Susan; Smith, Walter

    2016-04-01

    Global Collaborative STEM Education, as the name suggests, simultaneously supports two sets of knowledge and skills. The first set is STEM -- science, technology, engineering and math. The other set of content knowledge and skills is that of global collaboration. Successful global partnerships require awareness of one's own culture, the biases embedded within that culture, as well as developing awareness of the collaborators' culture. Workforce skills fostered include open-mindedness, perseverance when faced with obstacles, and resourceful use of technological "bridges" to facilitate and sustain communication. In respect for the 2016 GIFT Workshop focus, Global Collaborative STEM Education projects dedicated to astronomy research will be presented. The projects represent different benchmarks within the Global Collaborative STEM Education continuum, culminating in an astronomy research experience that fully reflects how the global STEM workforce collaborates. To facilitate wider engagement in Global Collaborative STEM Education, project summaries, classroom resources and contact information for established international collaborative astronomy research projects will be disseminated.

  1. Development of the Meharry Medical College Prostate Cancer Research Program

    National Research Council Canada - National Science Library

    Ukoli, Flora A. M

    2006-01-01

    African Americans (AA) are disproportionately affected by prostate cancer (PCa) for reasons including, biologic tumor differences, genetic predisposition, differential exposures, lack of access to prostate specific antigen (PSA...

  2. Hedgehog Signaling in Prostate Development, Regeneration and Cancer

    Directory of Open Access Journals (Sweden)

    Wade Bushman

    2016-10-01

    Full Text Available The prostate is a developmental model system study of prostate growth regulation. Historically the research focus was on androgen regulation of development and growth and instructive interactions between the mesenchyme and epithelium. The study of Hh signaling in prostate development revealed important roles in ductal morphogenesis and in epithelial growth regulation that appear to be recapitulated in prostate cancer. This overview of Hh signaling in the prostate will address the well-described role of paracrine signaling prostate development as well as new evidence suggesting a role for autocrine signaling, the role of Hh signaling in prostate regeneration and reiterative activities in prostate cancer.

  3. Influence of catheterization on the prostate specific antigen level in patient suffering from prostate disorder

    OpenAIRE

    Osman Sianipar, Osman Sianipar

    2015-01-01

    Background: The increase of life expectancy may increase the number of patients suffered from prostate disorder. In Indonesia prostate cancer is in the top ten malignancies in men and is the second most frequent malignancies in urology clinics. Early detection may decreasies its fatality rate and increase the quality of life. Prostate specific antigen (PSA) is clinically the most useful tumor marker; its serum level has positive correlation with the prostate cancer. Serum PSA level will also ...

  4. From Prostate to Bone: Key Players in Prostate Cancer Bone Metastasis

    OpenAIRE

    Thobe, Megan N.; Rinker-Schaeffer, Carrie W.; Clark, Robert J.; Bainer, Russell O; Prasad, Sandip M.

    2011-01-01

    Bone is the most common site for metastasis in human prostate cancer patients. Skeletal metastases are a significant cause of morbidity and mortality and overall greatly affect the quality of life of prostate cancer patients. Despite advances in our understanding of the biology of primary prostate tumors, our knowledge of how and why secondary tumors derived from prostate cancer cells preferentially localize bone remains limited. The physiochemical properties of bone, and signaling molecules ...

  5. Tactile sensing of prostate cancer : a resonance sensor method evaluated using human prostate tissue in vitro

    OpenAIRE

    Jalkanen, Ville

    2007-01-01

    Prostate cancer is the most frequent type of cancer in men in Europe and the USA. The methods presently used to detect and diagnose prostate cancer are inexact, and new techniques are needed. Prostate tumours can be regarded as harder than the surrounding normal healthy glandular tissue, and therefore it is of interest to be able to reliably measure prostate tissue stiffness. In this dissertation the approach was to evaluate tactile resonance sensor technology and its ability to measure mecha...

  6. Effect of endocrine treatment on voiding and prostate size in men with prostate cancer

    DEFF Research Database (Denmark)

    Klarskov, Louise L; Klarskov, Peter; Mommsen, Søren

    2012-01-01

    The aim of this study was to assess and quantify changes in voiding parameters and prostate size in men with prostate cancer from before the start of endocrine treatment and during long-term follow-up.......The aim of this study was to assess and quantify changes in voiding parameters and prostate size in men with prostate cancer from before the start of endocrine treatment and during long-term follow-up....

  7. The Multifaceted Roles of STAT3 Signaling in the Progression of Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bishop, Jennifer L.; Thaper, Daksh; Zoubeidi, Amina, E-mail: azoubeidi@prostatecentre.com [The Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, 2660 Oak Street, Vancouver British Columbia, V6H 3Z6 (Canada)

    2014-04-09

    The signal transducer and activator of transcription (STAT)3 governs essential functions of epithelial and hematopoietic cells that are often dysregulated in cancer. While the role for STAT3 in promoting the progression of many solid and hematopoietic malignancies is well established, this review will focus on the importance of STAT3 in prostate cancer progression to the incurable metastatic castration-resistant prostate cancer (mCRPC). Indeed, STAT3 integrates different signaling pathways involved in the reactivation of androgen receptor pathway, stem like cells and the epithelial to mesenchymal transition that drive progression to mCRPC. As equally important, STAT3 regulates interactions between tumor cells and the microenvironment as well as immune cell activation. This makes it a major factor in facilitating prostate cancer escape from detection of the immune response, promoting an immunosuppressive environment that allows growth and metastasis. Based on the multifaceted nature of STAT3 signaling in the progression to mCRPC, the promise of STAT3 as a therapeutic target to prevent prostate cancer progression and the variety of STAT3 inhibitors used in cancer therapies is discussed.

  8. Prostate cancer detection rate in patients with fluctuating prostate-specific antigen levels on the repeat prostate biopsy

    OpenAIRE

    Park, Yong Hyun; Lee, Jung Keun; Jung, Jin-Woo; Lee, Byung Ki; Lee, Sangchul; Jeong, Seong Jin; Hong, Sung Kyu; Byun, Seok-Soo; Lee, Sang Eun

    2014-01-01

    Purpose: To evaluate whether the risk of prostate cancer was different according to the pattern of fluctuation in prostate-specific antigen (PSA) levels in patients undergoing repeat transrectal ultrasound-guided prostate biopsy (TRUS-Bx). Methods: From March 2003 to December 2012, 492 patients underwent repeat TRUS-Bx. The patients were stratified into 3 groups based on the PSA fluctuation pattern: group 1 (continuous elevation of PSA, n=169), group 2 (PSA fluctuation with PSA velocity [PSAV...

  9. Interleukin-6 and prostate cancer: Current developments and unsolved questions.

    Science.gov (United States)

    Culig, Zoran; Puhr, Martin

    2017-03-16

    Interleukin (IL)-6 is a pro-inflammatory cytokine that is expressed in prostate tumors and in the stromal tumor micro-enviroment. It is known to regulate proliferation, apoptosis, angiogenesis, and differentiation. The signaling pathway of Janus kinase and signal transducer and activator of transcription (STAT)3, which is activated by IL-6, is in the focus of scientific investigations for improved treatment approaches. Different effects of IL-6 and/or STAT3 on tumor cell growth have been observed in human and murine prostate cancer (PCa) models. Experimental therapies have been proposed in order to block the IL-6/STAT3 signaling pathway. In this context, the anti-IL-6 antibody siltuximab (CNTO 328) has been demonstrated to inhibit growth of prostate tumors in vitro and in vivo and delays progression towards castration resistance. However, clinically, the anti-IL-6 antibody was not successful as a monotherapy in phase II studies in patients with metastatic PCa. IL-6 is implicated in regulation of cellular stemness by increasing phosphorylation of STAT3. The cytokine has also a role in development of resistance to the non-steroidal anti-androgen enzalutamide. Endogenous inhibitors of IL-6 are suppressors of cytokine signaling and protein inhibitors of activated STAT. Although they inhibit signal transduction through STAT3, they may also exhibit anti-apoptotic effects. On the basis of complexity of IL-6 action in PCa, an individualized approach is needed to identify patients who will benefit from anti-IL-6 therapy in combination with standard treatments. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Gene therapy for prostate cancer.

    LENUS (Irish Health Repository)

    Tangney, Mark

    2012-01-31

    Cancer remains a leading cause of morbidity and mortality. Despite advances in understanding, detection, and treatment, it accounts for almost one-fourth of all deaths per year in Western countries. Prostate cancer is currently the most commonly diagnosed noncutaneous cancer in men in Europe and the United States, accounting for 15% of all cancers in men. As life expectancy of individuals increases, it is expected that there will also be an increase in the incidence and mortality of prostate cancer. Prostate cancer may be inoperable at initial presentation, unresponsive to chemotherapy and radiotherapy, or recur following appropriate treatment. At the time of presentation, patients may already have metastases in their tissues. Preventing tumor recurrence requires systemic therapy; however, current modalities are limited by toxicity or lack of efficacy. For patients with such metastatic cancers, the development of alternative therapies is essential. Gene therapy is a realistic prospect for the treatment of prostate and other cancers, and involves the delivery of genetic information to the patient to facilitate the production of therapeutic proteins. Therapeutics can act directly (eg, by inducing tumor cells to produce cytotoxic agents) or indirectly by upregulating the immune system to efficiently target tumor cells or by destroying the tumor\\'s vasculature. However, technological difficulties must be addressed before an efficient and safe gene medicine is achieved (primarily by developing a means of delivering genes to the target cells or tissue safely and efficiently). A wealth of research has been carried out over the past 20 years, involving various strategies for the treatment of prostate cancer at preclinical and clinical trial levels. The therapeutic efficacy observed with many of these approaches in patients indicates that these treatment modalities will serve as an important component of urological malignancy treatment in the clinic, either in isolation or

  11. Stem Cells in Neuroendocrinology

    National Research Council Canada - National Science Library

    Pfaff, Donald; Christen, Yves

    2016-01-01

    This volume starts with an elementary introduction covering stem cell methodologies used to produce specific types of neurons, possibilities for their therapeutic use, and warnings of technical problems...

  12. Integrative STEM Education Defined

    OpenAIRE

    Sanders, Mark E.

    2015-01-01

    “My work with integrative STEM education began in 1990 with the NSF-funded Technology, Science, Mathematics Integration Project… By 2008, I was convinced “STEM Education” was (and always would be) a hopelessly ambiguous phrase, and therefore felt we absolutely needed to rename our “STEM Education” graduate program and develop a tight operational definition of the central idea underlying our program, in hopes of preventing the sort of hopeless ambiguity that ruined the term “STEM education” fr...

  13. Cancer stem cell metabolism

    National Research Council Canada - National Science Library

    Peiris-Pagès, Maria; Martinez-Outschoorn, Ubaldo E; Pestell, Richard G; Sotgia, Federica; Lisanti, Michael P

    2016-01-01

    .... Cancer stem cells also seem to adapt their metabolism to microenvironmental changes by conveniently shifting energy production from one pathway to another, or by acquiring intermediate metabolic phenotypes...

  14. Stress and stem cells.

    Science.gov (United States)

    Tower, John

    2012-01-01

    The unique properties and functions of stem cells make them particularly susceptible to stresses and also lead to their regulation by stress. Stem cell division must respond to the demand to replenish cells during normal tissue turnover as well as in response to damage. Oxidative stress, mechanical stress, growth factors, and cytokines signal stem cell division and differentiation. Many of the conserved pathways regulating stem cell self-renewal and differentiation are also stress-response pathways. The long life span and division potential of stem cells create a propensity for transformation (cancer) and specific stress responses such as apoptosis and senescence act as antitumor mechanisms. Quiescence regulated by CDK inhibitors and a hypoxic niche regulated by FOXO transcription factor function to reduce stress for several types of stem cells to facilitate long-term maintenance. Aging is a particularly relevant stress for stem cells, because repeated demands on stem cell function over the life span can have cumulative cell-autonomous effects including epigenetic dysregulation, mutations, and telomere erosion. In addition, aging of the organism impairs function of the stem cell niche and systemic signals, including chronic inflammation and oxidative stress. Copyright © 2012 Wiley Periodicals, Inc.

  15. Malakoplakia of the prostate diagnosed by elevated PSA level and transrectal prostate biopsy

    Directory of Open Access Journals (Sweden)

    Sacit Nuri Görgel

    2011-04-01

    Full Text Available Malakoplakia is an inflammation which is thought to develop secondary to chronic Escherichia coli infections. Although often seen in the genitourinary tract, it can also be seen in colon, stomach, lung, liver, bone, uterus, and skin. In this case report, we present prostatic malakoplakia diagnosed by elevated prostate-specific antigen level and transrectal prostate biopsy.

  16. African Americans' Perceptions of Prostate-Specific Antigen Prostate Cancer Screening

    Science.gov (United States)

    Hunter, Jaimie C.; Vines, Anissa I.; Carlisle, Veronica

    2015-01-01

    Background: In 2012, the U.S. Preventive Services Task Force released a hotly debated recommendation against prostate-specific antigen testing for all men. The present research examines African Americans' beliefs about their susceptibility to prostate cancer (PCa) and the effectiveness of prostate-specific antigen testing in the context of the…

  17. Prostate Cancer Screening : The effect on prostate cancer mortality and incidence

    NARCIS (Netherlands)

    P.J. van Leeuwen (Pim)

    2012-01-01

    textabstractAt first glance, deciding whether to get the PSA screening test for prostate cancer seems to be pretty straightforward and attractive. It’s a simple blood test that can pick up the prostate cancer long before your symptoms appear. After all, your prostate cancer is earlier treated

  18. Comparison of Two Prostate Cancer Risk Calculators that Include the Prostate Health Index

    NARCIS (Netherlands)

    M.J. Roobol-Bouts (Monique); M.M. Vedder (Moniek); D. Nieboer (Daan); A. Houlgatte (Alain); S. Vincendeau (Sébastien); M. Lazzeri (Massimo); G. Guazzoni (Giorgio); C. Stephan (Carsten); A. Semjonow (Axel); A. Haese (Alexander); M. Graefen (Markus); E.W. Steyerberg (Ewout)

    2015-01-01

    textabstractBackground: Risk prediction models for prostate cancer (PCa) have become important tools in reducing unnecessary prostate biopsies. The Prostate Health Index (PHI) may increase the predictive accuracy of such models. Objectives: To compare two PCa risk calculators (RCs) that include PHI.

  19. TISSUE POLYPEPTIDE-SPECIFIC ANTIGEN - A DISCRIMINATIVE PARAMETER BETWEEN PROSTATE-CANCER AND BENIGN PROSTATIC HYPERTROPHY

    NARCIS (Netherlands)

    MARRINK, J; OOSTEROM, R; BONFRER, HMG; SCHRODER, FH; MENSINK, HJA

    1993-01-01

    The serum concentration of the cell proliferation marker TPS (tissue polypeptide-specific antigen) was compared with the tumour marker PSA (prostate specific antigen). PSA was found elevated in 50% of the benign prostatic hypertrophy (BPH) patients, in 88% of the patients with active prostate cancer

  20. Empirical estimates of prostate cancer overdiagnosis by age and prostate-specific antigen

    NARCIS (Netherlands)

    A.J. Vickers (Andrew); D. Sjoberg (Daniel); D. Ulmert (David); E. Vertosick (Emily); M.J. Roobol-Bouts (Monique); I.M. Thompson (Ian); E.A.M. Heijnsdijk (Eveline); H.J. de Koning (Harry); C. Atoria-Swartz (Coral); P.T. Scardino (Peter); H. Lilja (Hans)

    2014-01-01

    textabstractBackground: Prostate cancer screening depends on a careful balance of benefits, in terms of reduced prostate cancer mortality, and harms, in terms of overdiagnosis and overtreatment. We aimed to estimate the effect on overdiagnosis of restricting prostate specific antigen (PSA) testing

  1. Fear of prostate biopsy: a limitation in the management of prostate ...

    African Journals Online (AJOL)

    The incidence of prostate cancer is increasing in the country and now constitutes 11% of allmale cancers. For diagnosis of prostate cancer, a histological diagnosis is necessary and this requires that a prostate biopsy be performed but patientsmay not readily accept this invasive procedure. A 2-year retrospective study was ...

  2. Psychosocial Consequences of Overdiagnostic of Prostate Cancer

    DEFF Research Database (Denmark)

    Nielsen, Sigrid Brisson; Brodersen, John

    Psychosocial Consequences of Overdiagnostic of Prostate Cancer Sigrid Brisson Nielsen & John Brodersen Introduction In Denmark there are approximately 4400 men diagnosed with prostate cancer each year and nearly 1200 men dies of this disease yearly. The incidence of prostate cancer has increased...... for the past twenty years and make up 24 % of all cancer incidents in men. However, the mortality of prostate cancer has not changed in line with this increase. Empirical evidence shows that the increase in incidence of prostate cancer in Denmark without an increase in the mortality is mostly caused...... by opportunistic PSA screening in General Practice. It is recommended that men ≥ 60 year old diagnosed with prostate cancer and a Gleason score ≤ 6 are monitored with active surveillance. This is due to the probability of this type of cancer metastasizing is very small as approximately 90 % of them is assumed...

  3. Prostate cancer and inflammation: the evidence

    Science.gov (United States)

    Sfanos, Karen S; De Marzo, Angelo M

    2014-01-01

    Chronic inflammation is now known to contribute to several forms of human cancer, with an estimated 20% of adult cancers attributable to chronic inflammatory conditions caused by infectious agents, chronic noninfectious inflammatory diseases and / or other environmental factors. Indeed, chronic inflammation is now regarded as an ‘enabling characteristic’ of human cancer. The aim of this review is to summarize the current literature on the evidence for a role for chronic inflammation in prostate cancer aetiology, with a specific focus on recent advances regarding the following: (i) potential stimuli for prostatic inflammation; (ii) prostate cancer immunobiology; (iii) inflammatory pathways and cytokines in prostate cancer risk and development; (iv) proliferative inflammatory atrophy (PIA) as a risk factor lesion to prostate cancer development; and (v) the role of nutritional or other antiinflammatory compounds in reducing prostate cancer risk. PMID:22212087

  4. Microwave surgical treatment of diseases of prostate

    Energy Technology Data Exchange (ETDEWEB)

    Harada, T.; Etori, K.; Kumazaki, T.; Nishizawa, O.; Noto, H.; Tsuchida, S.

    1985-12-01

    A new transurethral probe for microwave radiation of the prostate has been developed. As a preliminary experiment, sliced ham was radiated with microwaves using this probe in order to evaluate the extent of thermal effect. Using mongrel male dogs, microwave coagulation of the prostate was examined. These animal experiments showed marked destruction of the prostate gland. Furthermore, the safety of this method was confirmed on the basis of results from the experiments. Prostatic bladder neck obstruction also has been treated in 6 patients with benign prostatic hypertrophy or carcinoma of the prostate by this technique. There has been no mortality and also no complications. The results of this preliminary clinical trial have been excellent.

  5. Prostatic stromal microenvironment and experimental diabetes

    Directory of Open Access Journals (Sweden)

    DL Ribeiro

    2009-06-01

    Full Text Available The diabetes causes alterations in various organ systems, including the male accessory sex glands. The prostate is very important in the reproductive process and it is a frequent target of malignant changes. The aim of this work was to demonstrate the histochemical and ultrastructural alterations in the prostate of diabetic animals. Two groups of animals were utilized: control and non-obese diabetic mice (NOD. Twelve days after the characterization of diabetic status the ventral prostate was collected, fixed in Karnovsky and paraformaldehyde, processed for histochemistry and TEM associated to stereology. The results showed reduction of the epithelial area and increasing of the stromal area with muscular and collagen hypertrophy in the prostatic gland. It was characterized the development of prostatic intraepithelial neoplasia, inflammatory processes and dilation of the organelles involved in the secretory process. It was concluded that diabetes besides damaging the reproductive process, affects the glandular homeostasis favoring the development of prostatic pathologies.

  6. Balloon dilatation of the prostatic urethra

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Yeon Soo; Shim, Hyung Jin; Cha, Kyung Soo; Hong, Ju Hee; Lim, Myung Ah; Kim, Cheol Soo [Sung Ae General Hospital, Seoul (Korea, Republic of)

    1991-03-15

    We analyzed the result of transurethral balloon dilatation in 11 patients with benign prostatic hypertrophy. The procedures were performed under intravenous sedation and local anesthesia with double lumen balloon catheter at 4 atmosphere for 10 minutes. After dilatation, the prostatism symptom scores improved in 10 out of 11 patients and the mean diameter of the prostatic urethra significantly increased form 4.3 mm to 10.2 mm ({rho} < 0.005). The procedures were successful not only in lateral lobe hypertrophy but also in median lobe hypertrophy of the prostate. Postdilatation MRI of 1 patient showed an intact prostatic capsule and no periprostatic hematoma. Complications did not develop except in 1 patient with mild hematuria and incontinence. These preliminary results suggest that transurethral balloon dilatation can be an effective and safe treatment modality for benign prostatic hypertrophy.

  7. Development of New Treatments for Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    DiPaola, R. S.; Abate-Shen, C.; Hait, W. N.

    2005-02-01

    The Dean and Betty Gallo Prostate Cancer Center (GPCC) was established with the goal of eradicating prostate cancer and improving the lives of men at risk for the disease through research, treatment, education and prevention. GPCC was founded in the memory of Dean Gallo, a beloved New Jersey Congressman who died tragically of prostate cancer diagnosed at an advanced stage. GPCC unites a team of outstanding researchers and clinicians who are committed to high-quality basic research, translation of innovative research to the clinic, exceptional patient care, and improving public education and awareness of prostate cancer. GPCC is a center of excellence of The Cancer Institute of New Jersey, which is the only NCI-designated comprehensive cancer center in the state. GPCC efforts are now integrated well as part of our Prostate Program at CINJ, in which Dr. Robert DiPaola and Dr. Cory Abate-Shen are co-leaders. The Prostate Program unites 19 investigators from 10 academic departments who have broad and complementary expertise in prostate cancer research. The overall goal and unifying theme is to elucidate basic mechanisms of prostate growth and oncogenesis, with the ultimate goal of promoting new and effective strategies for the eradication of prostate cancer. Members' wide range of research interests collectively optimize the chances of providing new insights into normal prostate biology and unraveling the molecular pathophysiology of prostate cancer. Cell culture and powerful animal models developed by program members recapitulate the various stages of prostate cancer progression, including prostatic intraepithelial neoplasia, adenocarcinoma, androgen-independence, invasion and metastases. These models promise to further strengthen an already robust program of investigator-initiated therapeutic clinical trials, including studies adopted by national cooperative groups. Efforts to translate laboratory results into clinical studies of early detection and

  8. Dystrophic Calcification of the Prostate after Cryotherapy

    Directory of Open Access Journals (Sweden)

    Christopher Dru

    2014-01-01

    Full Text Available We present a previously undocumented complication of dystrophic calcification of the prostate after cryotherapy. An 87-year-old male presented with recurrent lower urinary tract infections and was found to have an obstructing large calcified mass in the right lobe of the prostate. Subsequently, he underwent transurethral resection of the prostate (TURP and bladder neck with laser lithotripsy to remove the calculus. We propose that chronic inflammation and necrosis of the prostate from cryotherapy resulted in dystrophic calcification of the prostate. As the use of cryotherapy for the treatment of localized prostate cancer continues to increase, it is important that clinicians be aware of this scenario and the technical challenges it poses.

  9. The role of prolactin in prostatic inflammation

    Directory of Open Access Journals (Sweden)

    Edson João da Silva

    2013-12-01

    Full Text Available Several reports have shown that prolactin (PRL plays a role in prostatic growth, but few studies considered the role of PRL in the process of prostatic inflammation. Young (45 ± 5 days old and adult (75 ± 5 days old male Wistar rats were subcutaneously injected daily with domperidone (4.0 mg.kg-1 to maintain high serum PRL levels. The animals were treated for 15, 30, 45 or 60 days. Blood and prostate samples were collected at the end of each treatment for PRL dosage and histological analysis, respectively. Only young animals treated with DOMP for 15 and 30 days displayed inflammatory infiltrate in the prostate. These results confirm literature data in regards to PRL involvement in inducing prostate inflammation. Moreover, it was concluded that young animals are more susceptible then adults to the PRL action concerning prostate inflammation.

  10. The impact of obesity towards prostate diseases

    Directory of Open Access Journals (Sweden)

    Dyandra Parikesit

    2016-03-01

    Full Text Available Evidence has supported obesity as a risk factor for both benign prostate hyperplasia (BPH and prostate cancer (PCa. Obesity causes several mechanisms including increased intra-abdominal pressure, altered endocrine status, increased sympathetic nervous activity, increased inflammation process, and oxidative stress, all of which are favorable in the development of BPH. In PCa, there are several different mechanisms, such as decreased serum testosterone, peripheral aromatization of androgens, insulin resistance, and altered adipokine secretion caused by inflammation, which may precipitate the development of and even cause high-grade PCa. The role of obesity in prostatitis still remains unclear. A greater understanding of the pathogenesis of prostate disease and adiposity could allow the development of new therapeutic markers, prognostic indicators, and drug targets. This review was made to help better understanding of the association between central obesity and prostate diseases, such as prostatitis, BPH, and PCa.

  11. [Transurethral plasmakinetic enucleation of the prostate for benign prostatic hyperplasia].

    Science.gov (United States)

    Sheng, Xu-jun; Chen, Jian-hua; Wang, Wei-ming; Kong, Liang; Zhang, Liang; Yu, Yong-jiang; Wu, Yu; Qi, Jun

    2011-05-01

    To evaluate clinical application of transurethral plasmakinetic enucleation of the prostate (PKEP) to the treatment of benign prostatic hyperplasia (BPH). A total of 90 BPH patients, aged 59-83 (mean 71) years and with indication of surgery, underwent transurethral resection of the prostate (the TURP group, n=50) and transurethral plasmakinetic enucleation of the prostate (the PKEP group, n=40), respectively. We recorded and analyzed the preoperative prostate volume, IPSS, QOL and Qmax, operation time, intra- and post-operative bleeding and complications, postoperative continuous bladder irrigation, and IPSS, QOL and Qmax at 2 weeks and 6 months after surgery. The preoperative prostate volume and operation time were 58.9 g and 58.8 min in the TURP group versus 58.3 g and 93.0 min in the PKEP group. Mild transurethral resection syndrome (TURS) appeared in 2 TURP receivers, while no abnormality was found in electrocardiogram monitoring in those undergoing PKEP. Continuous bladder irrigation was necessitated in 3 and urgent incontinence of urine occurred in 4 cases of TURP, as compared with 1 and 4 cases in the PKEP group. None of the 90 patients needed blood transfusion. At 2 weeks before and after surgery and 6 months postoperatively, IPSS averaged 19.7, 11.6 and 5.1, QOL 4.6, 3.3 and 1.1, and Qmax 6.3, 13.0 and 18.1 ml/s in the TURP group versus 18.6, 8.4 and 4.9 (IPSS), 4.5, 2.7 and 1.1 (QOL) and 6.9, 14.2 and 19.0 ml/s (Qmax) in the PKEP group. There were significant differences in operation time, IPSS and QOL at 2 weeks postoperatively between the two groups, as well as in IPSS, QOL and Qmax at 6 months before and after surgery (P 0.01). Transurethral PKEP is a safe, effective and thorough surgical method to be chosen for the treatment of BPH.

  12. miR-409-3p/-5p promotes tumorigenesis, epithelial to mesenchymal transition and bone metastasis of human prostate cancer

    Science.gov (United States)

    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

  13. miR-409-3p/-5p promotes tumorigenesis, epithelial-to-mesenchymal transition, and bone metastasis of human prostate cancer.

    Science.gov (United States)

    Josson, Sajni; Gururajan, Murali; Hu, Peizhen; Shao, Chen; Chu, GinaChia-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

    2014-09-01

    miR-409-3p/-5p is a miRNA 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 biologic impact of manipulation of miR-409-3p/-5p on prostate cancer progression and correlated the levels of its expression with clinical human prostate cancer bone metastatic specimens. miRNA profiling of a prostate cancer bone metastatic epithelial-to-mesenchymal transition (EMT) cell line model was performed. A Gleason score human tissue array was probed for validation of specific miRNAs. In addition, genetic manipulation of miR-409-3p/-5p was performed to determine its role in tumor growth, EMT, and bone metastasis in mouse models. 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 progression-free survival of patients with prostate cancer. 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 with control vehicle-treated cells. miR-409-3p/-5p plays an important role in prostate cancer biology by facilitating tumor growth, EMT, and bone metastasis. This finding bears particular translational importance as miR-409-3p/-5p appears to be an attractive biomarker and/or possibly a therapeutic target to treat bone metastatic prostate cancer. ©2014 American Association for Cancer Research.

  14. Prostate Cancer Genetics in African Americans

    Science.gov (United States)

    2015-11-01

    AWARD NUMBER: W81XWH-11-1-0566 TITLE: Prostate Cancer Genetics in African Americans PRINCIPAL INVESTIGATOR: Henry T. Lynch, MD CONTRACTING...in the African American community in Nebraska and Mississippi. Family history of prostate and other cancers is being recorded with the purpose of...W81XWH-11-1-0566 November 2015 Final 15Aug2011 - 14Aug2015 Prostate Cancer Genetics in African Americans Henry T. Lynch Nothing listed 36

  15. Primary prostatic leiomyosarcoma in an adult

    Directory of Open Access Journals (Sweden)

    Naresh K Agarwal

    2006-01-01

    Full Text Available Leiomyosarcoma of prostate is rare accounting for 0.1% of prostatic malignancies. It has a very poor prognosis although rate of survival is variable. Treatment recommendations are difficult to establish due to the rarity of the tumour. Here we report a case of primary prostatic leiomyosarcoma in an adult treated by primary excision of mass followed by doxorubicin based chemotherapy. Patient subsequently developed local recurrence and disseminated secondaries and was then lost to follow up.

  16. Targeting Prostate Cancer with Multifunctional Nanoparticles

    Science.gov (United States)

    2015-10-01

    AWARD NUMBER: W81XWH-14-1-0487 TITLE: Targeting Prostate Cancer with Multifunctional Nanoparticles PRINCIPAL INVESTIGATOR: Darryl Martin...Targeting Prostate Cancer with Multifunctional Nanoparticles 5b. GRANT NUMBER W81XWH-14-1-0487 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Darryl...claudin-3 and claudin-4 are expressed in subsets of aggressive prostate cancer. Finally, we produced our first two batches of nanoparticles during year

  17. Overexpression of vimentin in canine prostatic carcinoma

    DEFF Research Database (Denmark)

    Rodrigues, M M P; Rema, A; Gärtner, F

    2011-01-01

    is associated with the invasive phenotype of human prostate cancer cells. The aim of the present study was to characterize immunohistochemically the expression of vimentin by canine prostatic carcinomas. Primary carcinomas and metastatic tumour foci both showed vimentin expression. This finding suggests...... that the acquisition of the epithelial-mesenchymal transition phenotype in canine prostatic carcinoma may be characterized by the presence of mesenchymal intermediate filament (vimentin) that could lead to a higher likelihood of metastasis....

  18. Targeting the Neural Microenvironment in Prostate Cancer

    Science.gov (United States)

    2017-10-01

    Award Number: W81XWH-14-1-0505 TITLE: Targeting the Neural Microenvironment in Prostate Cancer PRINCIPAL INVESTIGATOR: Michael Ittmann MD PhD...CONTRACT NUMBER Targeting the Neural Microenvironment in Prostate Cancer 5b. GRANT NUMBER W81XWH-14-1-0505 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d...ABSTRACT Prostate cancer (PCa) remains the most common malignancy and the second leading cause of cancer -related death for men in the United States. Recent

  19. Prostate Cancer Genetics in African Americans

    Science.gov (United States)

    2014-09-01

    hereditary prostate cancer syndrome. This will be possible through the recruitment of a total of 800 African Americans who have been diagnosed with...community in Nebraska and Mississippi. Family history of prostate and other cancers is being recorded with the purpose of identifying any hereditary ...Omaha, their geographic area of most concentration in Nebraska. Information on prostate cancer predisposing genes in African Americans are partially

  20. Molecular Characterization of Indolent Prostate Cancer

    Science.gov (United States)

    2016-12-01

    prostate-specific antigen ( PSA ) test, and treated aggressively following diagnosis, leading to the contemporary problem of prostate cancer over-diagnosis... PSA ᝺ng/m; Gleason score <=6; and no more than 2 cores containing cancer, and <=50% of core involved with cancer; PSA density ɘ.15ng/ml/g). A...Applications: Title: Reducing Prostate Cancer Overdiagnosis and Overtreatment (NIH P01, PI : Pienta) Supporting Agency: NIH/NCI Performance Period

  1. Wnt/β-catenin Signaling in Normal and Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Kenneth C. Valkenburg

    2011-04-01

    Full Text Available The ability of Wnt ligands to initiate a signaling cascade that results in cytoplasmic stabilization of, and nuclear localization of, β-catenin underlies their ability to regulate progenitor cell differentiation. In this review, we will summarize the current knowledge of the mechanisms underlying Wnt/β-catenin signaling and how the pathway regulates normal differentiation of stem cells in the intestine, mammary gland, and prostate. We will also discuss how dysregulation of the pathway is associated with putative cancer stem cells and the potential therapeutic implications of regulating Wnt signaling.

  2. Cancer exosomes trigger mesenchymal stem cell differentiation into pro-angiogenic and pro-invasive myofibroblasts

    OpenAIRE

    Chowdhury, Ridwana; Webber, Jason P.; Gurney, Mark; Mason, Malcolm David; Tabi, Zsuzsanna; Clayton, Aled

    2015-01-01

    Stromal fibroblasts become altered in response to solid cancers, to exhibit myofibroblastic characteristics, with disease promoting influence. Infiltrating mesenchymal stem cells (MSC) may contribute towards these changes, but the factors secreted by cancer cells that impact MSC differentiation are poorly understood.\\ud \\ud We investigated the role of nano-metre sized vesicles (exosomes), secreted by prostate cancer cells, on the differentiation of bone-marrow MSC (BM-MSC), and the subsequent...

  3. ROPE Registry Project to Determine the Safety and Efficacy of Prostate Artery Embolisation (PAE) for Lower Urinary Tract Symptoms Secondary to Benign Prostatic Enlargement (LUTS BPE).

    Science.gov (United States)

    2016-08-03

    Lower Urinary Tract Symptoms Caused by Benign Prostatic Enlargement (LUTS BPE); Prostate Artery Embolisation (PAE); Transurethral Resection of the Prostate (TURP); Open Prostatectomy; Laser Enucleation or Ablation of the Prostate

  4. Stem Cell Transplants (For Teens)

    Science.gov (United States)

    ... Situations Talking to Your Parents - or Other Adults Stem Cell Transplants KidsHealth > For Teens > Stem Cell Transplants Print ... Does it Take to Recover? Coping What Are Stem Cells? As you probably remember from biology class, every ...

  5. Prospective Analysis on the Relation between Pain and Prostate Volume during Transrectal Prostate Biopsy

    Energy Technology Data Exchange (ETDEWEB)

    Yun, Tae Jin; Lee, Hak Jong; Kim, Seung Hyup; Lee, Sang Eun; Byun, Seok Soo; Hong, Sung Kyu; Cho, Jeong Yeon; Seong, Chang Kyu [Seoul National University Bundang Hospital, Institute of Radiation Medicine, Seoul (Korea, Republic of)

    2007-06-15

    We wanted to assess the relationship between pain and the prostate volume during transrectal ultrasound (TRUS) guided biopsy. Between July and September 2006, 71 patients scheduled for TRUS biopsy of the prostate were considered for inclusion to this study. These patients underwent periprostatic neurovascular bundle block with lidocaine prior to biopsy. Pain was assessed using a Visual Analogue Scale (VAS) during periprostatic neurovascular bundle block (VAS 1), during biopsy (VAS 2), and 20 minutes after biopsy (VAS 3). The mean pain scores were analyzed in the large prostate group (prostate volume > 40 cc) and the small prostate group (prostate volume {<=} 40 cc). P values < 0.05 were considered significant. The mean prostate volume was 42.2 cc (standard deviation: 8.6). The mean pain scores of VAS 1, 2 and 3 were 4.70 {+-} 1.61, 3.15 {+-}2.44 and 1.05 {+-} 1.51, respectively. In the large prostate group, the mean pains scores of VAS 1, 2 and 3 were 4.75 {+-} 1.76, 3.51 {+-} 2.76 and 1.29 {+-} 1.70, respectively, whereas in the small prostate group, the means pain scores were 4.66 {+-} 1.46, 2.77 {+-} 2.0, and 0.80 {+-} 1.26, respectively. Although there were no statistical differences of VAS 1, the larger prostate group revealed higher pain scores of VAS 2 and 3 compared with the small prostate group (p < 0.05). Patients with larger prostate volumes tend to feel more pain during and after TRUS guided prostate biopsy. Our findings suggest that additional analgesic strategies may be necessary when the patients with larger prostate undergo TRUS guided prostate biopsy.

  6. Emphysematous prostatic abscess with rectoprostatic fistula

    Directory of Open Access Journals (Sweden)

    Po-Cheng Chen

    2014-12-01

    Full Text Available Emphysematous prostatic abscess is a rare but relatively serious infectious disease, and its association with rectoprostatic fistula is extremely unusual. The reported risk factors for this condition include diabetes mellitus, immunosuppression, and prostate surgery. We report a rare case of emphysematous prostatic abscess successfully treated by transurethral drainage. Nonetheless, a rectoprostatic fistula was found postoperatively. The fistula healed spontaneously without fasting or fecal diversion after suprapubic cystostomy and placement of a urethral catheter. This case highlights the importance of surgical drainage for the treatment of an emphysematous prostatic abscess and that conservative treatment can be a safe and effective approach for an associated rectoprostatic fistula.

  7. Spindle-cell carcinoma of the prostate

    Directory of Open Access Journals (Sweden)

    Carlos Hirokatsu Watanabe Silva

    2012-03-01

    Full Text Available Sarcoma of the prostate and sarcomatoid carcinoma of the prostate are rareconditions, both characterized by a poor prognosis. Sarcomatoid carcinoma ofthe prostate typically arises from the evolution of an underlying adenocarcinoma,occasionally featuring heterologous elements, bulky disease being possiblebut rare. In contrast, sarcoma of the prostate derives from non-epithelialmesenchymal components of the prostatic stroma, shows rapid growth, andfrequently presents as massive pelvic tumors obstructing the urinary tractat the time of diagnosis. We report the case of a 55-year-old patient with atwo-month history of symptoms of urinary obstruction. The patient presentedwith an extremely enlarged heterogeneous prostate, although his prostatespecificantigen level was low. The lack of a history of prostatic neoplasia ledus to suspect sarcoma, and a transrectal prostate biopsy was carried out. Animmunohistochemical study of the biopsy specimen did not confirm the clinicalsuspicion. However, in view of the clinical features, we believe that sarcoma ofthe prostate was the most likely diagnosis. The patient received neoadjuvantchemotherapy followed by radiation therapy. At this writing, surgical resectionhad yet to be scheduled.

  8. SYSTEMS MODELING OF PROSTATE REGULATION AND ...

    Science.gov (United States)

    The prostate is an androgen-dependent tissue that is an important site of disease in human males as well as an important indicator of androgen status in animals. The rat prostate is used for studying antiandrogenic drugs as well as for evaluation of endocrine disruption (e.g., Hershberger Assay). Pubertal changes in the prostate have been observed to be as sensitive to environmental antiandrogens as in utero effects. The goal of this research is to model the biology of prostate androgen function on a systems level to determine the factors responsible for the dose-response observable with androgens and antiandrogens in the male rat. This includes investigation of the roles of positive and negative feedback loops in prostatic response following castration and dosing with testosterone and/or antiandrogens. A biologically-based, systems-level model will be developed describing the regulation of the prostate by androgens. The model will extend an existing model for the male rat central axis, which describes feedback between luteinizing hormone and testosterone production in the testes, to include the prostate and conversion of testosterone to dihydrotestosterone (DHT). The prostate model will describe binding of androgens to the androgen receptor, 5α-reductase catalyzed production of DHT, and gene regulation affecting cell proliferation, apoptosis, and prostatic fluid production. The model will combine pharmacokinetic models for endogenous hormones (i.e., testost

  9. Robotic Prostate Biopsy in Closed MRI Scanner

    National Research Council Canada - National Science Library

    Fischer, Gregory

    2008-01-01

    .... This work enables prostate brachytherapy and biopsy procedures in standard high-field diagnostic MRI scanners through the development of a robotic needle placement device specifically designed...

  10. Bullous pemphigoid associated with prostate adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Öztürkcan Serap

    2004-01-01

    Full Text Available Bullous pemphigoid is a common autoimmune skin disease characterized by the presence of subepidermal blisters. It has been associated with underlying neoplasia in isolated reports. A 78-year-old man with generalized blisters was diagnosed as bullous pemphigoid on clinical, histopathological and direct immunofluorescence grounds. His free and total prostate specific antigen (PSA levels were high and histopathological examination of a prostate specimen revealed prostate adenocarcinoma. We present this rare case to discuss the possible association between bullous pemphigoid and prostate adenocarcinoma.

  11. Dietary Genistein and Prostate Cancer Chemoprevention

    National Research Council Canada - National Science Library

    Lamartiniere, Coral

    2003-01-01

    .... We have previously demonstrated that genistein is bioavailable to the rat prostate and that life-time exposure to physiological concentrations of genistein suppressed the development of chemically...

  12. Dietary Genistein and Prostate Cancer Chemoprevention

    National Research Council Canada - National Science Library

    Lamartiniere, Coral

    2004-01-01

    .... We have previously demonstrated that genistein is bioavailable to the rat prostate and that life-time exposure to physiological concentrations of genistein suppressed the development of chemically...

  13. Immunotherapy and Immune Evasion in Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Thakur, Archana, E-mail: thakur@karmanos.org; Vaishampayan, Ulka [Department of Oncology, Wayne State University, Detroit, MI 48201 (United States); Lum, Lawrence G., E-mail: thakur@karmanos.org [Department of Oncology, Wayne State University, Detroit, MI 48201 (United States); Department of Medicine, Wayne State University, Detroit, MI 48201 (United States); Department of Immunology and Microbiology, Wayne State University, Detroit, MI 48201 (United States)

    2013-05-24

    Metastatic prostate cancer remains to this day a terminal disease. Prostatectomy and radiotherapy are effective for organ-confined diseases, but treatment for locally advanced and metastatic cancer remains challenging. Although advanced prostate cancers treated with androgen deprivation therapy achieves debulking of disease, responses are transient with subsequent development of castration-resistant and metastatic disease. Since prostate cancer is typically a slowly progressing disease, use of immune-based therapies offers an advantage to target advanced tumors and to induce antitumor immunity. This review will discuss the clinical merits of various vaccines and immunotherapies in castrate resistant prostate cancer and challenges to this evolving field of immune-based therapies.

  14. Baseline Prostate Atrophy is Associated with Reduced Risk of Prostate Cancer in Men Undergoing Repeat Prostate Biopsy.

    Science.gov (United States)

    Moreira, Daniel M; Bostwick, David G; Andriole, Gerald L; Peterson, Bercedis L; Cohen, Harvey J; Castro-Santamaria, Ramiro; Freedland, Stephen J

    2015-11-01

    We evaluated whether the presence and severity of baseline prostate atrophy in men with initial biopsy negative for prostate cancer was associated the risk of subsequent prostate cancer detection in a clinical trial with scheduled study mandated biopsies. We retrospectively analyzed the records of 3,084 men 50 to 75 years old with prostate specific antigen between 2.5 and 10 ng/ml, and a prior negative biopsy in the placebo arm of the REDUCE (Reduction by Dutasteride of Prostate Cancer Events) study who completed at least 1 per-protocol biopsy. Prostate cancer (defined as present or absent) and prostate atrophy (graded as absent, mild or moderate/marked) was assessed by central pathology review. The association of baseline atrophy with positive 2 and 4-year repeat biopsies was evaluated with logistic regression, controlling for baseline covariates. Baseline prostate atrophy was detected in 2,143 men (70%) and graded as mild and moderate/marked in 1,843 (60%) and 300 (10%) baseline biopsies, respectively. Patients with atrophy were older and had a larger prostate, and more acute and chronic prostate inflammation. At 2-year biopsy the prostate cancer incidence was 17% (508 cases). Baseline atrophy was significantly associated with lower prostate cancer risk (univariable and multivariable OR 0.60, 95% CI 0.50-0.74 and OR 0.67, 95% CI 0.54-0.83, p biopsy. These results were similar at the 4-year biopsy (univariable and multivariable OR 0.70, 95% CI 0.53-0.93 and OR 0.72, 95% CI 0.53-0.97, p = 0.03, respectively). Relative to no atrophy the prostate cancer risk at the 2-year repeat biopsy was lower for mild atrophy (OR 0.69, 95% CI 0.55-0.86) and moderate/marked atrophy (OR 0.51, 95% CI 0.34-0.76, each p biopsy negative for prostate cancer was independently associated with subsequent lower prostate cancer detection. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  15. A Rare Prostatic Diagnosis of an Old Man: A Pure Prostatic Leiomyoma

    Directory of Open Access Journals (Sweden)

    W. M. van Ulden-Bleumink

    2013-01-01

    Full Text Available A pure leiomyoma of the prostate is a rare benign tumor. An 82-year-old man was referred to our urology department with gross hematuria and complete urinary retention. Examination revealed a benign prostatic hyperplasia. Transrectal ultrasound showed a prostate of 125 mL. Serum PSA was 1.9 µg/L. A simple retropubic prostatectomy was performed. Histopathological examination showed a pure leiomyoma of the prostate, without the presence of glandular prostate tissue. The diagnosis, characteristics, and treatment of this tumor are described.

  16. STEM Careers Ambassadors

    Science.gov (United States)

    Eaton, Denise

    2011-01-01

    This article is designed to help teachers feel more confident in their work with STEM Ambassadors to further enhance enrichment activities. Skills shortages in Science, Technology, Engineering, Maths (STEM) and the Built Environment are well documented, and will continue to be an issue whether people are in a period of recession or recovery. The…

  17. Teaching STEM by Design

    Science.gov (United States)

    Billiar, Kristen; Hubelbank, Jeanne; Oliva, Thomas; Camesano, Terri

    2014-01-01

    Developing innovative science, technology, engineering and mathematics (STEM) curricula that elicit student excitement for learning is a continuous challenge for K-12 STEM teachers. Generating these lessons while meeting conflicting pedagogical objectives and constraints of time, content, and cost from various parties is truly a challenging task…

  18. Dazlin' pluripotent stem cells

    NARCIS (Netherlands)

    Welling, M.A.

    2014-01-01

    Pluripotent embryonic stem cells (ESCs) can be isolated from the inner cell mass (ICM) of blastocyst embryos and differentiate into all three germ layers in vitro. However, despite their similar origin, mouse embryonic stem cells represent a more naïve ICM-like pluripotent state whereas human

  19. Designing for STEM Integration

    Science.gov (United States)

    Berland, Leema K.

    2013-01-01

    We are increasingly seeing an emphasis on STEM integration in high school classrooms such that students will learn and apply relevant math and science content while simultaneously developing engineering habits of mind. However, research in both science education and engineering education suggests that this goal of truly integrating STEM is rife…

  20. Cancer stem cells revisited

    NARCIS (Netherlands)

    Batlle, Eduard; Clevers, Hans

    2017-01-01

    The cancer stem cell (CSC) concept was proposed four decades ago, and states that tumor growth, analogous to the renewal of healthy tissues, is fueled by small numbers of dedicated stem cells. It has gradually become clear that many tumors harbor CSCs in dedicated niches, and yet their

  1. Aneuploidy in stem cells

    NARCIS (Netherlands)

    Garcia-Martinez, Jorge; Bakker, Bjorn; Schukken, Klaske M; Simon, Judith E; Foijer, Floris

    2016-01-01

    Stem cells hold enormous promise for regenerative medicine as well as for engineering of model systems to study diseases and develop new drugs. The discovery of protocols that allow for generating induced pluripotent stem cells (IPSCs) from somatic cells has brought this promise steps closer to

  2. A Unique Cellular and Molecular Microenvironment Is Present in Tertiary Lymphoid Organs of Patients with Spontaneous Prostate Cancer Regression

    Directory of Open Access Journals (Sweden)

    María de la Luz García-Hernández

    2017-05-01

    Full Text Available ObjectiveMultiple solid cancers contain tertiary lymphoid organs (TLO. However, it is unclear whether they promote tumor rejection, facilitate tumor evasion, or simply whether they are a byproduct of chronic inflammation. We hypothesize that although chronic inflammation induces TLO formation, the tumor milieu can modulate TLO organization and functions in prostate cancer. Therefore, our study seeks to elucidate the cellular and molecular signatures in unique prostatectomy specimens from evanescent carcinoma patients to identify markers of cancer regression, which could be harnessed to modulate local immunosuppression or potentially enhance TLO function.MethodsWe used multicolor immunofluorescence to stain prostate tissues, collected at different stages of cancer progression (prostatic intraepithelial neoplasia, intermediate and advanced cancer or from patients with evanescent prostate carcinoma. Tissues were stained with antibodies specific for pro-inflammatory molecules (cyclooxygenase 2, CXCL10, IL17, tumor-infiltrating immune cells (mature DC-LAMP+ dendritic cells, CD3+ T cells, CD3+Foxp3+ regulatory T cells (Treg, T bet+ Th1 cells, granzyme B+ cytotoxic cells, and stromal cell populations (lymphatic vessels, tumor neovessels, high endothelial venules (HEV, stromal cells, which promote prostate tumor growth or are critical components of tumor-associated TLO.ResultsGenerally, inflammatory cells are located at the margins of tumors. Unexpectedly, we found TLO within prostate tumors from patients at different stages of cancer and in unique samples from patients with spontaneous cancer remission. In evanescent prostate carcinomas, accumulation of Treg was compromised, while Tbet+ T cells and CD8 T cells were abundant in tumor-associated TLO. In addition, we found a global decrease in tumor neovascularization and the coverage by cells positive for cyclooxygenase 2 (COX2. Finally, consistent with tumor regression, prostate stem cell antigen was

  3. Expanding STEM Education | Poster

    Science.gov (United States)

    Editor’s note: This article is written as a reflection on experiential STEM education by a student who completed her Werner H. Kirsten internship in June 2015. Here, she advocates for incorporating hands-on experience into STEM curricula. If the only way for high school students to learn science, technology, engineering, and mathematics (STEM) is through textbooks, then count me out. But how then do you get students to learn STEM outside of the classroom? The focus of this article is to advocate for high school STEM education through experiential learning. Tom Freston, one of the founders and the chief executive officer (CEO) of MTV Productions, said in an interview in Men’s Journal that “innovation is taking two things that already exist and...

  4. Parathyroid hormone related-protein promotes epithelial-to-mesenchymal transition in prostate cancer.

    Directory of Open Access Journals (Sweden)

    Weg M Ongkeko

    Full Text Available Parathyroid hormone-related protein (PTHrP possesses a variety of physiological and developmental functions and is also known to facilitate the progression of many common cancers, notably their skeletal invasion, primarily by increasing bone resorption. The purpose of this study was to determine whether PTHrP could promote epithelial-to-mesenchymal transition (EMT, a process implicated in cancer stem cells that is critically involved in cancer invasion and metastasis. EMT was observed in DU 145 prostate cancer cells stably overexpressing either the 1-141 or 1-173 isoform of PTHrP, where there was upregulation of Snail and vimentin and downregulation of E-cadherin relative to parental DU 145. By contrast, the opposite effect was observed in PC-3 prostate cancer cells where high levels of PTHrP were knocked-down via lentiviral siRNA transduction. Increased tumor progression was observed in PTHrP-overexpressing DU 145 cells while decreased progression was observed in PTHrP-knockdown PC-3 cells. PTHrP-overexpressing DU 145 formed larger tumors when implanted orthoptopically into nude mice and in one case resulted in spinal metastasis, an effect not observed among mice injected with parental DU 145 cells. PTHrP-overexpressing DU 145 cells also caused significant bone destruction when injected into the tibiae of nude mice, while parental DU 145 cells caused little to no destruction of bone. Together, these results suggest that PTHrP may work through EMT to promote an aggressive and metastatic phenotype in prostate cancer, a pathway of importance in cancer stem cells. Thus, continued efforts to elucidate the pathways involved in PTHrP-induced EMT as well as to develop ways to specifically target PTHrP signaling may lead to more effective therapies for prostate cancer.

  5. From Prostate to Bone: Key Players in Prostate Cancer Bone Metastasis

    Directory of Open Access Journals (Sweden)

    Megan N. Thobe

    2011-01-01

    Full Text Available Bone is the most common site for metastasis in human prostate cancer patients. Skeletal metastases are a significant cause of morbidity and mortality and overall greatly affect the quality of life of prostate cancer patients. Despite advances in our understanding of the biology of primary prostate tumors, our knowledge of how and why secondary tumors derived from prostate cancer cells preferentially localize bone remains limited. The physiochemical properties of bone, and signaling molecules including specific chemokines and their receptors, are distinct in nature and function, yet play intricate and significant roles in prostate cancer bone metastasis. Examining the impact of these facets of bone metastasis in vivo remains a significant challenge, as animal models that mimic the natural history and malignant progression clinical prostate cancer are rare. The goals of this article are to discuss (1 characteristics of bone that most likely render it a favorable environment for prostate tumor cell growth, (2 chemokine signaling that is critical in the recruitment and migration of prostate cancer cells to the bone, and (3 current animal models utilized in studying prostate cancer bone metastasis. Further research is necessary to elucidate the mechanisms underlying the extravasation of disseminated prostate cancer cells into the bone and to provide a better understanding of the basis of cancer cell survival within the bone microenvironment. The development of animal models that recapitulate more closely the human clinical scenario of prostate cancer will greatly benefit the generation of better therapies.

  6. From Prostate to Bone: Key Players in Prostate Cancer Bone Metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Thobe, Megan N. [Section of Urology, Department of Surgery, The University of Chicago, Chicago, IL 60637 (United States); Clark, Robert J. [Department of Molecular Pathogenesis and Molecular Medicine, The University of Chicago, Chicago, IL 60637 (United States); Bainer, Russell O. [Department of Human Genetics, The University of Chicago, Chicago, IL 60637 (United States); Prasad, Sandip M.; Rinker-Schaeffer, Carrie W., E-mail: crinkers@uchicago.edu [Section of Urology, Department of Surgery, The University of Chicago, Chicago, IL 60637 (United States)

    2011-01-27

    Bone is the most common site for metastasis in human prostate cancer patients. Skeletal metastases are a significant cause of morbidity and mortality and overall greatly affect the quality of life of prostate cancer patients. Despite advances in our understanding of the biology of primary prostate tumors, our knowledge of how and why secondary tumors derived from prostate cancer cells preferentially localize bone remains limited. The physiochemical properties of bone, and signaling molecules including specific chemokines and their receptors, are distinct in nature and function, yet play intricate and significant roles in prostate cancer bone metastasis. Examining the impact of these facets of bone metastasis in vivo remains a significant challenge, as animal models that mimic the natural history and malignant progression clinical prostate cancer are rare. The goals of this article are to discuss (1) characteristics of bone that most likely render it a favorable environment for prostate tumor cell growth, (2) chemokine signaling that is critical in the recruitment and migration of prostate cancer cells to the bone, and (3) current animal models utilized in studying prostate cancer bone metastasis. Further research is necessary to elucidate the mechanisms underlying the extravasation of disseminated prostate cancer cells into the bone and to provide a better understanding of the basis of cancer cell survival within the bone microenvironment. The development of animal models that recapitulate more closely the human clinical scenario of prostate cancer will greatly benefit the generation of better therapies.

  7. Prostatic intraepithelial neoplasia-like ductal prostatic adenocarcinoma: A case suitable for active surveillance?

    Directory of Open Access Journals (Sweden)

    Soroush Rais-Bahrami

    2017-01-01

    Full Text Available In contrast to typical prostatic ductal adenocarcinoma, prostatic intraepithelial neoplasia (PIN-like ductal adenocarcinoma is a rare variant of prostate cancer with low-grade clinical behavior. We report a case of a 66-year-old African-American male with an elevated serum prostate-specific antigen who underwent multiparametric prostate magnetic resonance imaging (MRI and MRI/ultrasound fusion-guided biopsies. Pathology demonstrated low-volume Gleason score 3 + 3 = 6 (Grade Group 1, acinar adenocarcinoma involving one core and PIN-like ductal adenocarcinoma on a separate core. Herein, we discuss the potential role of active surveillance for patients with this rare variant of prostate cancer found in the era of advanced imaging with multiparametric MRI for prostate cancer.

  8. Novel Oncogene Induced Metastatic Prostate Cancer Cell Lines Define Human Prostate Cancer Progression Signatures

    Science.gov (United States)

    Ju, Xiaoming; Ertel, Adam; Casimiro, Mathew; Yu, Zuoren; Meng, Hui; McCue, Peter A.; Walters, Rhonda; Fortina, Paolo; Lisanti, Michael P.; Pestell, Richard G.

    2013-01-01

    Herein, murine prostate cancer cell lines, generated via selective transduction with a single oncogene (c-Myc, Ha-Ras, and v-Src), demonstrated oncogene-specific prostate cancer molecular signatures that were recapitulated in human prostate cancer, and developed lung metastasis in immune competent mice. Interrogation of two independent retrospective cohorts of patient samples using the oncogene signature demonstrated an ability to distinguish tumor from normal prostate with a predictive value for prostate cancer of 98 – 99%. In a blinded study, the signature algorithm demonstrated independent substratification of reduced recurrence free survival by Kaplan-Meier analysis. The generation of new oncogene-specific prostate cancer cell lines that recapitulate human prostate cancer gene expression, that metastasize in immune-competent mice, are a valuable new resource for testing targeted therapy while the molecular signatures identified herein provides further value over current gene signature markers of prediction and outcome. PMID:23204233

  9. New concepts in tissue specificity for prostate cancer and benign prostatic hyperplasia.

    Science.gov (United States)

    De Marzo, A M; Coffey, D S; Nelson, W G

    1999-03-01

    Of the hundreds of species of mammals, all of which have prostate glands, only humans and dogs are known to suffer from benign prostatic hyperplasia (BPH) and prostate carcinoma. In humans, prostate carcinoma is common, yet carcinomas of other sex accessory tissues are rare. In addition, different anatomic regions within the prostate gland have very different rates of BPH and carcinoma. In this article, we explore ideas and potential mechanisms relating to these paradoxical findings that may help explain the species, organ, and zone specificity of BPH and prostate cancer. We present an evolutionary argument that attempts to relate a high-fat diet, with its potential for generating oxidative DNA damage, to the species selectivity of prostate cancer. In addition, we outline an argument based on our preliminary studies indicating that chronic inflammation and the associated increase in cell turnover in the setting of increased oxidative stress may help to account for the organ selectivity of genitourinary carcinomas.

  10. Cytokeratin 18 Is Not Required for Morphogenesis of Developing Prostates but Contributes to Adult Prostate Regeneration

    Directory of Open Access Journals (Sweden)

    Chenlu Zhang

    2013-01-01

    Full Text Available Cytokeratin 18 (CK18 is a key component of keratin-containing intermediate filaments and has long been used as a classic luminal cell marker in prostatic tissue. However, the in vivo function of CK18 in prostate is not known so far. We reported in this study, unexpectedly, that deletion of CK18 in a mouse model did not affect the morphological or the histological structures of adult prostate, as the CK18 knockout prostate displayed a normal glandular ductal structure, branching pattern, and composition of both luminal and basal cells. However, CK18 loss compromised the regenerative tubular branching in dorsolateral prostate after castration and androgen replacement. Therefore, in contrast to its importance as luminal cell marker, CK18 is dispensable for the prostate morphogenesis but contributes to adult prostate regeneration.

  11. Prostate cancer outcome in Burkina Faso

    Directory of Open Access Journals (Sweden)

    Yameogo Clotaire

    2011-09-01

    Full Text Available Abstract Introduction African-American black men race is one of non-modifiable risk factors confirmed for prostate cancer. Many studies have been done in USA among African- American population to evaluate prostate cancer disparities. Compared to the USA very few data are available for prostate cancer in Sub-Saharan African countries. The objective of this study was to describe incident prostate cancer (PC diagnosis characteristics in Burkina Faso (West Africa. Methods We performed a prospective non randomized patient’s cohort study of new prostate cancer cases diagnosed by histological analysis of transrectal prostate biopsies in Burkina Faso. Study participants included 166 patients recruited at the urology division of the university hospital of Ouagadougou. Age of the patients, clinical symptoms, digital rectal examination (DRE result, serum prostate-specific antigen (PSA level, histological characteristics and TNM classification were taking in account in this study. Results 166 transrectal prostate biopsies (TRPB were performed based on high PSA level or abnormal DRE. The prostate cancer rate on those TRPB was 63, 8 % (n=106. The mean age of the patients was 71, 5 years (52 to 86. Urinary retention was the first clinical patterns of reference in our institution (55, 7 %, n = 59. Most patients, 56, 6 % (n = 60 had a serum PSA level over than 100 ng/ml. All the patients had adenocarcinoma on histological study of prostate biopsy cores. The majority of cases (54, 7 % n = 58 had Gleason score equal or higher than 7. Conclusion Prostate cancer is diagnosed at later stages in our country. Very high serum PSA level and poorly differentiated tumors are the two major characteristics of PC at the time of diagnosis.

  12. Extraglandular and intraglandular vascularization of canine prostate.

    Science.gov (United States)

    Stefanov, Miroslav

    2004-03-01

    The literature on the vascularization of the canine prostate is reviewed and the clinical significance of prostate morphology is described. Scanning Electron Microscopy (SEM), combined with improved corrosion casting methods, reveal new morphological details that promise better diagnostics and treatment but also require expansion of clinical nomenclature. A proposal is made for including two previously unnamed veins in Nomina Anatomica Veterinaria (NAV). The canine prostate has two lobes with independent vascularization. Each lobe is supplied through the left and right a. prostatica, respectively. The a. prostatica sprouts three small vessels (cranial, middle, and caudal) towards the prostate gland. A. prostatica is a small-size artery whose wall structure is similar to the arteries of the muscular type. V. prostatica is a small-size valved vein. The canine prostate has capsular, parenchymal, and urethral vascular zones. The surface vessels of the capsule are predominantly veins and the diameter of arterial vessels is larger than that of the veins. The trabecular vessels are of two types: direct and branched. The prostate parenchyma is supplied by branches of the trabecular vessels. The periacinary capillaries are fenestrated and form a net in a circular pattern. The processes of the myoepithelial cells embrace both the acins and the periacinar capillaries. In the prostate ductal system. there are spermatozoa. The prostatic part of the urethra is supplied by an independent branch of a. prostatica. The prostatic urethral part is drained by v. prostatica, the vein of the urethral bulb and the ventral prostate veins. M. urethralis begins as early as the urethral prostatic part. The greater part of the white muscle fibers in m. urethralis suggest an enhanced anaerobic metabolism. Copyright 2004 Wiley-Liss, Inc.

  13. KLK-targeted Therapies for Prostate Cancer.

    Science.gov (United States)

    Hannu, Koistinen; Johanna, Mattsson; Ulf-Håkan, Stenman

    2014-09-01

    Alternative treatments are urgently needed for prostate cancer, especially to address the aggressive metastatic castration-resistant disease. Proteolytic enzymes are involved in cancer growth and progression. The prostate produces several proteases, the most abundant ones being two members of the kallikrein-related peptidase (KLK) family, prostate-specific antigen (PSA) and KLK2. Despite the wide use of PSA as a clinical marker, the function(s) of PSA and other KLKs in prostate cancer are poorly known. Hypothetic roles of KLKs in prostate cancer include activities that may both promote and inhibit cancer growth and metastasis, including the antiangiogenic activity of PSA. Thus it may be possible to control prostate cancer growth by modulating the proteolytic activities of KLKs. PSA and KLK2 are especially attractive targets for prostate cancer treatment because of their proposed roles in tumor development and inhibition of angiogenesis in combination with their prostate selective expression. So far the number of molecules affecting selectively the activity of KLKs is limited and none of these are used to treat prostate cancer. Prodrugs that, after cleavage of the peptide part by PSA or KLK2, release active drug molecules, and PSA-targeted therapeutic vaccines have already been tested clinically in humans and the first results have been encouraging. Although KLKs are attractive targets for prostate cancer treatment, much remains to be done before their potential can be fully elucidated. The objective of this review is to address the current state of the KLKs as novel therapeutic targets for prostate cancer treatment.

  14. Prostate radiation in non-metastatic castrate refractory prostate cancer provides an interesting insight into biology of prostate cancer

    Directory of Open Access Journals (Sweden)

    Pascoe Abigail C

    2012-03-01

    Full Text Available Abstract Background The natural history of non-metastatic castrate refractory prostate cancer is unknown and treatment options are limited. We present a retrospective review of 13 patients with locally advanced or high risk prostate cancer, initially treated with hormone monotherapy and then treated with prostate radiation after becoming castration refractory. Findings Median PSA response following prostate radiation was 67.4%. Median time to biochemical progression following radiotherapy was 15 months and to detection of metastatic disease was 18.5 months. Median survival from castration resistance (to date of death or November 2011 was 60 months, with median survival from RT 42 months. Conclusion Prostate radiation appears to be beneficial even in patients with potential micrometastatic disease, which supports the hypothesis that the primary tumour is important in the progression of prostate cancer. These results are an interesting addition to the literature on the biology of prostate cancer especially as this data is unlikely to be available in the future due to combined prostate radiation and androgen deprivation therapy now being the standard of care.

  15. [Evalution of benign prostatic hyperplasia].

    Science.gov (United States)

    Desgrandchamps, François

    2005-11-01

    Benign prostatic hyperplasia is a disorder of aging men and according to reasons for consultation its incidence is continually increasing in parallel with the constant increase in life expectancy. Recommendations about its management have been made by numerous national and international, scientific authorities and those responsible for public health. However, despite a rationale based on regularly published data, there are many disparities between them and they are only partially followed up in routine practice. The purpose of a working group during the "2nd Interfaces in Urology" was to make a new assessment on this disorder with regard to the most recent data and existing recommendations, in order to offer clinicians a clearer attitude for the prescription of the initial evaluation of benign prostatic hyperplasia.

  16. Integrin Inhibitors in Prostate Cancer

    OpenAIRE

    Maylein C. Juan-Rivera; Magaly Martínez-Ferrer

    2018-01-01

    Prostate cancer (PCa) is the most frequently diagnosed cancer and the third highest cause of cancer-related deaths in men in the U.S. The development of chemotherapeutic agents that can bind PCa tumor cells with high specificity is critical in order to increase treatment effectiveness. Integrin receptors and their corresponding ligands have different expression patterns in PCa cells. They have been identified as promising targets to inhibit pathways involved in PCa progression. Currently, sev...

  17. Vaccine Immunotherapy for Prostate Cancer

    Science.gov (United States)

    2006-07-01

    cells. J. of Immunol., 150 :1458, 1993 15. Aoki, T, Tashiro K, Miyatake S, et al. Expression of murine interleukin 7 in a murine glioma cell in...antigen in patients with prostate cancer. Urology 51: 150 -157, 1998 30. Correale P, Walmsley K, Zaremba S, et al. Generation of human cytolytic T... Proteinuria Possibly AP010 GU 21 Proteinuria No AP016 GU 172 Left nephrolithiasis No AP016 GU 183 New primary tumor – papillary bladder No AP019 GU 1

  18. Vaccine Immunotherapy for Prostate Cancer

    Science.gov (United States)

    2011-05-01

    suddenly prior to study treatment. And one patient previously reported as a screen failure became eligible a nd was trea ted. This subject was not...of three study injections on the 08/12/10. Had a history of periodontal disease, ear pain, a bunion, ankle pain, kidn ey stones and prostate cancer...did not infor m the research unit nursing staff in the inpatient unit about this, but instead revealed this to the study team in the morning prior

  19. Microsatellite instability in prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Shan, A.L.; Wick, M.J.; Persons, D.L. [Mayo Clinic and Foundation, Rochester, MN (United States)] [and others

    1994-09-01

    Microsatellite instability (MIN) has been documented in hereditary nonpolyposis colorectal cancer (HNPCC) as well as in sporadic forms of human cancers. Two of the genes which appear to be responsible for this particular tumor phenotype, hMSH2 and hMLH1, have now been identified. To determine the potential role of these mutator genes in prostate cancer, we have examined 95 prostate adenocarcinomas (40 paraffin embedded and 55 fresh frozen) for the presence of genetic instability at four microsatellite markers. The markers are localized to chromosome arms 5q(APC-CA1), 8p(Mfd 210Z), 15q(635/636), and 17q(p53-CA). Patients from whom paraffin embedded material was obtained were divided into short term (<3 years, n=18), and long term (>3 years, n=22) survivors. Of the 95 tumors examined, only four tumors (4%) demonstrated MIN: two tumors demonstrated MIN at 3 loci (p53-CA, APC-CA1, 635/636), one tumor demonstrated MIN at 2 loci (APC-CA1 and 635/636), and one tumor demonstrated instability at 635/636 only. All tumors exhibiting MIN had Gleason scores of {ge} 4+4. A correlation between MIN and survival was not observed. Information on family history was limited. However, of the two patients demonstrating MIN at three loci, one patient was diagnosed with a second malignancy (TCC of the ureter), but otherwise had a negative family history, while the second patient had one first degree relative with esophageal cancer. The patient demonstrating MIN at two loci had a negative family history, while the remaining patient had two first degree relatives with cancer (prostate and stomach). These results suggest that hMSH2 and hMLH1 (as reflected by the small percentage of tumors displaying MIN) do not play a prominent role in the process of prostate tumorigenesis.

  20. Antioxidant Prophylaxis in the Prevention of Prostatic Intraepithelial Neoplasia (PIN)

    Science.gov (United States)

    2008-02-01

    Prevention of Prostatic Intraepithelial Neoplasia (PIN) PRINCIPAL INVESTIGATOR: A. Pratap Kumar, Ph.D...Prophylaxis in the Prevention of Prostatic Intraepithelial 5a. CONTRACT NUMBER Neoplasia (PIN) 5b. GRANT NUMBER W81XWH-04-1-0275 5c...Histopathological changes referred to as Prostatic Intraepithelial Neoplasia (PIN) are considered to be the most likely precursor of prostate cancer. The