WorldWideScience

Sample records for 1-integrin reverts prostate

  1. Inhibiting Vimentin or beta 1-integrin Reverts Prostate Tumor Cells in IrECM and Reduces Tumor Growth

    Zhang, Xueping; Fournier, Marcia V.; Ware, Joy L.; Bissell, Mina J.; Zehner, Zendra E.

    2009-07-27

    Prostate epithelial cells grown embedded in laminin-rich extracellular matrix (lrECM) undergo morphological changes that closely resemble their architecture in vivo. In this study, growth characteristics of three human prostate epithelial sublines derived from the same cellular lineage, but displaying different tumorigenic and metastatic properties in vivo, were assessed in three-dimensional (3D) lrECM gels. M12, a highly tumorigenic and metastatic subline, was derived from the parental prostate epithelial P69 cell line by selection in nude mice and found to contain a deletion of 19p-q13.1. The stable reintroduction of an intact human chromosome 19 into M12 resulted in a poorly tumorigenic subline, designated F6. When embedded in lrECM gels, the nontumorigenic P69 line produced acini with clearly defined lumena. Immunostaining with antibodies to {beta}-catenin, E-cadherin or {alpha}6-, {beta}4- and {beta}1-integrins showed polarization typical of glandular epithelium. In contrast, the metastatic M12 subline produced highly disorganized cells with no evidence of polarization. The F6 subline reverted to acini-like structures exhibiting basal polarity marked with integrins. Reducing either vimentin levels via siRNA interference or {beta}1-integrin expression by the addition of the blocking antibody, AIIB2, reorganized the M12 subline into forming polarized acini. The loss of vimentin significantly reduced M12-Vim tumor growth when assessed by subcutaneous injection in athymic mice. Thus, tumorigenicity in vivo correlated with disorganized growth in 3D lrECM gels. These studies suggest that the levels of vimentin and {beta}1-integrin play a key role in the homeostasis of the normal acini in prostate and that their dysregulation may lead to tumorigenesis.

  2. Inhibition of vimentin or B1 integrin reverts morphology of prostate tumor cells grown in laminin-rich extracellular matrix gels and reduces tumor growth in vivo

    Zhang, Xueping; Fournier, Marcia V; Ware, Joy L; Bissell, Mina J; Yacoub, Adly; Zehner, Zendra E

    2008-06-12

    Prostate epithelial cells grown embedded in laminin-rich extracellular matrix (lrECM) undergo morphologic changes that closely resemble their architecture in vivo. In this study, growth characteristics of three human prostate epithelial sublines derived from the same cellular lineage, but displaying different tumorigenic and metastatic properties in vivo, were assessed in three-dimensional lrECM gels. M12, a highly tumorigenic and metastatic subline, was derived from the immortalized, prostate epithelial P69 cell line by selection in athymic, nude mice and found to contain a deletion of 19p-q13.1. The stable reintroduction of an intact human chromosome 19 into M12 resulted in a poorly tumorigenic subline, designated F6. When embedded in lrECM gels, the parental, nontumorigenic P69 line produced acini with clearly defined lumena. Immunostaining with antibodies to {beta}-catenin, E-cadherin, or {alpha}6 and {beta}1 integrins showed polarization typical of glandular epithelium. In contrast, the metastatic M12 subline produced highly disorganized cells with no evidence of polarization. The F6 subline reverted to acini-like structures exhibiting basal polarity marked with integrins. Reducing either vimentin levels via small interfering RNA interference or the expression of {alpha}6 and {beta}1 integrins by the addition of blocking antibodies, reorganized the M12 subline into forming polarized acini. The loss of vimentin significantly reduced M12-Vim tumor growth when assessed by s.c. injection in athymic mice. Thus, tumorigenicity in vivo correlated with disorganized growth in three-dimensional lrECM gels. These studies suggest that the levels of vimentin and {beta}1 integrin play a key role in the homeostasis of the normal acinus in prostate and that their dysregulation may lead to tumorigenesis. [Mol Cancer Ther 2009;8(3):499-508].

  3. IGF-IR promotes prostate cancer growth by stabilizing α5β1 integrin protein levels.

    Aejaz Sayeed

    Full Text Available Dynamic crosstalk between growth factor receptors, cell adhesion molecules and extracellular matrix is essential for cancer cell migration and invasion. Integrins are transmembrane receptors that bind extracellular matrix proteins and enable cell adhesion and cytoskeletal organization. They also mediate signal transduction to regulate cell proliferation and survival. The type 1 insulin-like growth factor receptor (IGF-IR mediates tumor cell growth, adhesion and inhibition of apoptosis in several types of cancer. We have previously demonstrated that β1 integrins regulate anchorage-independent growth of prostate cancer (PrCa cells by regulating IGF-IR expression and androgen receptor-mediated transcriptional functions. Furthermore, we have recently reported that IGF-IR regulates the expression of β1 integrins in PrCa cells. We have dissected the mechanism through which IGF-IR regulates β1 integrin expression in PrCa. Here we report that IGF-IR is crucial for PrCa cell growth and that β1 integrins contribute to the regulation of proliferation by IGF-IR. We demonstrate that β1 integrin regulation by IGF-IR does not occur at the mRNA level. Exogenous expression of a CD4 - β1 integrin cytoplasmic domain chimera does not interfere with such regulation and fails to stabilize β1 integrin expression in the absence of IGF-IR. This appears to be due to the lack of interaction between the β1 cytoplasmic domain and IGF-IR. We demonstrate that IGF-IR stabilizes the β1 subunit by protecting it from proteasomal degradation. The α5 subunit, one of the binding partners of β1, is also downregulated along with β1 upon IGF-IR knockdown while no change is observed in the expression of the α2, α3, α4, α6 and α7 subunits. Our results reveal a crucial mechanistic role for the α5β1 integrin, downstream of IGF-IR, in regulating cancer growth.

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

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

    2016-01-01

    Resistance to docetaxel is a major clinical problem in advanced prostate cancer (PCa). Although glucocorticoids (GCs) are frequently used in combination with docetaxel, it is unclear to what extent GCs and their receptor, the glucocorticoid receptor (GR), contribute to the chemotherapy resistance. In this study, we aim to elucidate the role of the GR in docetaxel-resistant PCa in order to improve the current PCa therapies. GR expression was analyzed in a tissue microarray of primary PCa specimens from chemonaive and docetaxel-treated patients, and in cultured PCa cell lines with an acquired docetaxel resistance (PC3-DR, DU145-DR, and 22Rv1-DR). We found a robust overexpression of the GR in primary PCa from docetaxel-treated patients and enhanced GR levels in cultured docetaxel-resistant human PCa cells, indicating a key role of the GR in docetaxel resistance. The capability of the GR antagonists (RU-486 and cyproterone acetate) to revert docetaxel resistance was investigated and revealed significant resensitization of docetaxel-resistant PCa cells for docetaxel treatment in a dose- and time-dependent manner, in which a complete restoration of docetaxel sensitivity was achieved in both androgen receptor (AR)-negative and AR-positive cell lines. Mechanistically, we demonstrated down-regulation of Bcl-xL and Bcl-2 upon GR antagonism, thereby defining potential treatment targets. In conclusion, we describe the involvement of the GR in the acquisition of docetaxel resistance in human PCa. Therapeutic targeting of the GR effectively resensitizes docetaxel-resistant PCa cells. These findings warrant further investigation of the clinical utility of the GR antagonists in the management of patients with advanced and docetaxel-resistant PCa. PMID:26483423

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

    Kroon, Jan; Puhr, Martin; Buijs, Jeroen T.; Van Der Horst, Geertje; Lemhemmer, Daniël; Marijt, Koen A.; Hwang, Ming S.; Masood, Motasim; Grimm, Stefan; Storm, Gert; Metselaar, Josbert M.; Meijer, Onno C.; Culig, Zoran; Van Der Pluijm, Gabri

    2016-01-01

    Resistance to docetaxel is a major clinical problem in advanced prostate cancer (PCA). Although glucocorticoids (GCs) are frequently used in combination with docetaxel, it is unclear to what extent GCs and their receptor, the glucocorticoid receptor (GR), contribute to the chemotherapy resistance. I

  6. Gleditsia sinensis Thorn Attenuates the Collagen-Based Migration of PC3 Prostate Cancer Cells through the Suppression of α2β1 Integrin Expression

    Sujin Ryu

    2016-03-01

    Full Text Available Gleditsia sinensis thorns (GST have been used as a traditional medicine for carbuncles and skin diseases. The purpose of this study was to decide whether non-toxicological levels of water extract of GST (WEGST are effective in inhibiting the progress of prostate cancer formation and to identify the target molecule involved in the WEGST-mediated inhibitory process of prostate cancer cell migration and in vivo tumor formation. Through the Boyden chamber migration assay, we found that non-toxic levels of WEGST could not attenuate the PC3 migration to the bottom area coated with serum but significantly inhibited PC3 cell migration to the collagen-coated bottom area. We also found that non-toxic levels of WEGST significantly attenuated collagen against adhesion. Interestingly, ectopic administration of WEGST could not affect the expression of α2β1 integrin, which is known as a receptor of collagen. However, when the PC3 cells adhered to a collagen-coated plate, the expression of α2 integrin but not that of β1 integrin was significantly inhibited by the administration of non-toxic levels of WEGST, leading to the inhibition of focal adhesion kinase (FAK phosphorylation. Furthermore, oral administration of WEGST (25 mg/kg/day significantly inhibited the size of a PC3 cell-xenografted tumor. Taken together, these results suggest a novel molecular mechanism for WEGST to inhibit prostate cancer progression at particular stages, such as collagen-mediated adhesion and migration, and it might provide further development for the therapeutic use of WEGST in the treatment of prostate cancer progression.

  7. Genetic analysis of beta1 integrin "activation motifs" in mice

    Czuchra, Aleksandra; Meyer, Hannelore; Legate, Kyle R;

    2006-01-01

    /beta tails, leading to tail separation and integrin activation. We analyzed mice in which we mutated the tyrosines of the beta1 tail and the membrane-proximal aspartic acid required for the salt bridge. Tyrosine-to-alanine substitutions abolished beta1 integrin functions and led to a beta1 integrin...

  8. EC-70124, a Novel Glycosylated Indolocarbazole Multikinase Inhibitor, Reverts Tumorigenic and Stem Cell Properties in Prostate Cancer by Inhibiting STAT3 and NF-κB.

    Civenni, Gianluca; Longoni, Nicole; Costales, Paula; Dallavalle, Cecilia; García Inclán, Cristina; Albino, Domenico; Nuñez, Luz Elena; Morís, Francisco; Carbone, Giuseppina M; Catapano, Carlo V

    2016-05-01

    Cancer stem cells (CSC) contribute to disease progression and treatment failure in prostate cancer because of their intrinsic resistance to current therapies. The transcription factors NF-κB and STAT3 are frequently activated in advanced prostate cancer and sustain expansion of prostate CSCs. EC-70124 is a novel chimeric indolocarbazole compound generated by metabolic engineering of the biosynthetic pathways of glycosylated indolocarbazoles, such as staurosporine and rebeccamycin. In vitro kinome analyses revealed that EC-70124 acted as a multikinase inhibitor with potent activity against IKKβ and JAK2. In this study, we show that EC-70124 blocked concomitantly NF-κB and STAT3 in prostate cancer cells and particularly prostate CSCs, which exhibited overactivation of these transcription factors. Phosphorylation of IkB and STAT3 (Tyr705), the immediate targets of IKKβ and JAK2, respectively, was rapidly inhibited in vitro by EC-70124 at concentrations that were well below plasma levels in mice. Furthermore, the drug blocked activation of NF-κB and STAT3 reporters and suppressed transcription of their target genes. Treatment with EC-70124 impaired proliferation and colony formation in vitro and delayed development of prostate tumor xenografts. Notably, EC-70124 had profound effects on the prostate CSC subpopulation both in vitro and in vivo Thus, EC-70124 is a potent inhibitor of the NF-κB and STAT3 signaling pathways and blocked tumor growth and maintenance of prostate CSCs. EC-70124 may provide the basis for developing new therapeutic strategies that combine agents directed to the CSC component and the bulk tumor cell population for treatment of advanced prostate cancer. Mol Cancer Ther; 15(5); 806-18. ©2016 AACR. PMID:26826115

  9. β1 Integrins Mediate Mechanosensitive Signaling Pathways in Osteocytes

    Litzenberger, Julie B.; Tummala, Padmaja; Kim, Jae-Beom; Jacobs, Christopher R.

    2010-01-01

    Integrins are cell-substrate adhesion proteins that initiate intracellular signaling and may serve as mechanosensors in bone. MLO-Y4 cells were stably transfected with a dominant negative form of the β1 integrin subunit (β1DN) containing the transmembrane domain and cytoplasmic tail of β1 integrin. Cells expressing β1DN had reduced vinculin localization to focal contacts but no change in intracellular actin organization. When exposed to oscillatory fluid flow, β1DN cells exhibited a significa...

  10. β1 Integrin Is Essential for Teratoma Growth and Angiogenesis

    Bloch, Wilhelm; Forsberg, Erik; Lentini, Sylvia; Brakebusch, Cord; Martin, Karl; Krell, Hans W.; Weidle, Ulrich H.; Addicks, Klaus; Fässler, Reinhard

    1997-01-01

    Teratomas are benign tumors that form after ectopic injection of embryonic stem (ES) cells into mice and contain derivatives of all primitive germ layers. To study the role of β1 integrin during teratoma formation, we compared teratomas induced by normal and β1-null ES cells. Injection of normal ES cells gave rise to large teratomas. In contrast, β1-null ES cells either did not grow or formed small teratomas with an average weight of

  11. Beta 1 integrin is essential for teratoma growth and angiogenesis

    Bloch, W; Forsberg, E; Lentini, S;

    1997-01-01

    Teratomas are benign tumors that form after ectopic injection of embryonic stem (ES) cells into mice and contain derivatives of all primitive germ layers. To study the role of beta 1 integrin during teratoma formation, we compared teratomas induced by normal and beta1-null ES cells. Injection of...... normal ES cells gave rise to large teratomas. In contrast, beta 1-null ES cells either did not grow or formed small teratomas with an average weight of <5% of that of normal teratomas. Histological analysis of beta 1-null teratomas revealed the presence of various differentiated cells, however, a much...... lower number of host-derived stromal cells than in normal teratomas. Fibronectin, collagen I, and nidogen were expressed but, in contrast to normal teratomas, diffusely deposited in beta1-null teratomas. Basement membranes were present but with irregular shape and detached from the cell surface. Normal...

  12. The involvement of Gab1 and PI 3-kinase in β1 integrin signaling in keratinocytes

    The control of the stem cell compartment in epidermis is closely linked to the regulation of keratinocyte proliferation and differentiation. β1 integrins are expressed 2-fold higher by stem cells than transit-amplifying cells. Signaling from these β1 integrins is critical for the regulation of the epidermal stem cell compartment. To clarify the functional relevance of this differential expression of β1 integrins, we established HaCaT cells with high β1integrin expression by repeated flow cytometric sorting of this population from the parental cell line. In these obtained cells expressing β1 integrins by 5-fold, MAPK activation was markedly increased. Regarding the upstream of MAPK, Gab1 phosphorylation was also higher with high β1 integrin expression, while Shc phosphorylation was not altered. In addition, enhanced phosphatidylinositol 3-kinase activation was also observed. These observations suggest that Gab1 and phosphatidylinositol 3-kinase play pivotal roles in the β1 integrin-mediated regulation of the epidermal stem cell compartment

  13. β1 integrins regulate mammary gland proliferation and maintain the integrity of mammary alveoli

    Li, Na; Zhang, Yu; Naylor, Matthew J.; Schatzmann, Franziska; Maurer, Francisca; Wintermantel, Tim; Schuetz, Gunther; Mueller, Ulrich; Streuli, Charles H; Hynes, Nancy E.

    2005-01-01

    Integrin–extracellular matrix interactions play important roles in the coordinated integration of external and internal cues that are essential for proper development. To study the role of β1 integrin in the mammary gland, Itgβ1flox/flox mice were crossed with WAPiCre transgenic mice, which led to specific ablation of β1 integrin in luminal alveolar epithelial cells. In the β1 integrin mutant mammary gland, individual alveoli were disorganized resulting from alterations in cell–basement membr...

  14. Interactions between the discoidin domain receptor 1 and β1 integrin regulate attachment to collagen

    Lisa A. Staudinger

    2013-09-01

    Collagen degradation by phagocytosis is essential for physiological collagen turnover and connective tissue homeostasis. The rate limiting step of phagocytosis is the binding of specific adhesion receptors, which include the integrins and discoidin domain receptors (DDR, to fibrillar collagen. While previous data suggest that these two receptors interact, the functional nature of these interactions is not defined. In mouse and human fibroblasts we examined the effects of DDR1 knockdown and over-expression on β1 integrin subunit function. DDR1 expression levels were positively associated with enhanced contraction of floating and attached collagen gels, increased collagen binding and increased collagen remodeling. In DDR1 over-expressing cells compared with control cells, there were increased numbers, area and length of focal adhesions immunostained for talin, paxillin, vinculin and activated β1 integrin. After treatment with the integrin-cleaving protease jararhagin, in comparison to controls, DDR1 over-expressing cells exhibited increased β1 integrin cleavage at the cell membrane, indicating that DDR1 over-expression affected the access and susceptibility of cell-surface β1 integrin to the protease. DDR1 over-expression was associated with increased glycosylation of the β1 integrin subunit, which when blocked by deoxymannojirimycin, reduced collagen binding. Collectively these data indicate that DDR1 regulates β1 integrin interactions with fibrillar collagen, which positively impacts the binding step of collagen phagocytosis and collagen remodeling.

  15. Mycophenolate mofetil modulates adhesion receptors of the beta1 integrin family on tumor cells: impact on tumor recurrence and malignancy

    Beecken Wolf-Dietrich

    2005-01-01

    Full Text Available Abstract Background Tumor development remains one of the major obstacles following organ transplantation. Immunosuppressive drugs such as cyclosporine and tacrolimus directly contribute to enhanced malignancy, whereas the influence of the novel compound mycophenolate mofetil (MMF on tumor cell dissemination has not been explored. We therefore investigated the adhesion capacity of colon, pancreas, prostate and kidney carcinoma cell lines to endothelium, as well as their beta1 integrin expression profile before and after MMF treatment. Methods Tumor cell adhesion to endothelial cell monolayers was evaluated in the presence of 0.1 and 1 μM MMF and compared to unstimulated controls. beta1 integrin analysis included alpha1beta1 (CD49a, alpha2beta1 (CD49b, alpha3beta1 (CD49c, alpha4beta1 (CD49d, alpha5beta1 (CD49e, and alpha6beta1 (CD49f receptors, and was carried out by reverse transcriptase-polymerase chain reaction, confocal microscopy and flow cytometry. Results Adhesion of the colon carcinoma cell line HT-29 was strongly reduced in the presence of 0.1 μM MMF. This effect was accompanied by down-regulation of alpha3beta1 and alpha6beta1 surface expression and of alpha3beta1 and alpha6beta1 coding mRNA. Adhesion of the prostate tumor cell line DU-145 was blocked dose-dependently by MMF. In contrast to MMF's effects on HT-29 cells, MMF dose-dependently up-regulated alpha1beta1, alpha2beta1, alpha3beta1, and alpha5beta1 on DU-145 tumor cell membranes. Conclusion We conclude that MMF possesses distinct anti-tumoral properties, particularly in colon and prostate carcinoma cells. Adhesion blockage of HT-29 cells was due to the loss of alpha3beta1 and alpha6beta1 surface expression, which might contribute to a reduced invasive behaviour of this tumor entity. The enhancement of integrin beta1 subtypes observed in DU-145 cells possibly causes re-differentiation towards a low-invasive phenotype.

  16. Mycophenolate mofetil modulates adhesion receptors of the beta1 integrin family on tumor cells: impact on tumor recurrence and malignancy

    Tumor development remains one of the major obstacles following organ transplantation. Immunosuppressive drugs such as cyclosporine and tacrolimus directly contribute to enhanced malignancy, whereas the influence of the novel compound mycophenolate mofetil (MMF) on tumor cell dissemination has not been explored. We therefore investigated the adhesion capacity of colon, pancreas, prostate and kidney carcinoma cell lines to endothelium, as well as their beta1 integrin expression profile before and after MMF treatment. Tumor cell adhesion to endothelial cell monolayers was evaluated in the presence of 0.1 and 1 μM MMF and compared to unstimulated controls. beta1 integrin analysis included alpha1beta1 (CD49a), alpha2beta1 (CD49b), alpha3beta1 (CD49c), alpha4beta1 (CD49d), alpha5beta1 (CD49e), and alpha6beta1 (CD49f) receptors, and was carried out by reverse transcriptase-polymerase chain reaction, confocal microscopy and flow cytometry. Adhesion of the colon carcinoma cell line HT-29 was strongly reduced in the presence of 0.1 μM MMF. This effect was accompanied by down-regulation of alpha3beta1 and alpha6beta1 surface expression and of alpha3beta1 and alpha6beta1 coding mRNA. Adhesion of the prostate tumor cell line DU-145 was blocked dose-dependently by MMF. In contrast to MMF's effects on HT-29 cells, MMF dose-dependently up-regulated alpha1beta1, alpha2beta1, alpha3beta1, and alpha5beta1 on DU-145 tumor cell membranes. We conclude that MMF possesses distinct anti-tumoral properties, particularly in colon and prostate carcinoma cells. Adhesion blockage of HT-29 cells was due to the loss of alpha3beta1 and alpha6beta1 surface expression, which might contribute to a reduced invasive behaviour of this tumor entity. The enhancement of integrin beta1 subtypes observed in DU-145 cells possibly causes re-differentiation towards a low-invasive phenotype

  17. Revertant mosaicism in skin: natural gene therapy

    Joey E Lai-Cheong; McGrath, John A; Uitto, Jouni

    2010-01-01

    Revertant mosaicism is a naturally occurring phenomenon involving spontaneous correction of a pathogenic mutation in a somatic cell. Recent studies suggest that it is not a rare event and that it could be clinically relevant to phenotypic expression and patient treatment. Indeed, revertant cell therapy represents a potential “natural gene therapy” because in vivo reversion obviates the need for further genetic correction. Revertant mosaicism has been observed in several inherited conditions, ...

  18. Beta 1 integrin predicts survival in breast cancer: a clinicopathological and immunohistochemical study

    dos Santos Petra

    2012-08-01

    Full Text Available Abstract Background The main focus of several studies concerned with cancer progression and metastasis is to analyze the mechanisms that allow cancer cells to interact and quickly adapt with their environment. Integrins, a family of transmembrane glycoproteins, play a major role in invasive and metastatic processes. Integrins are involved in cell adhesion in both cell-extracellular matrix and cell-cell interactions, and particularly, β1 integrin is involved in proliferation and differentiation of cells in the development of epithelial tissues. This work aimed to investigate the putative role of β1 integrin expression on survival and metastasis in patients with breast invasive ductal carcinoma (IDC. In addition, we compared the expression of β1 integrin in patients with ductal carcinoma in situ (DCIS. Methods Through tissue microarray (TMA slides containing 225 samples of IDC and 67 samples of DCIS, β1 integrin expression was related with several immunohistochemical markers and clinicopathologic features of prognostic significance. Results β1 integrin was overexpressed in 32.8% of IDC. In IDC, β1 integrin was related with HER-2 (p = 0.019 and VEGF (p = 0.011 expression and it had a significant relationship with metastasis and death (p = 0.001 and p = 0.05, respectively. Kaplan-Meier survival analysis showed that the overexpression of this protein is very significant (p = 0.002 in specific survival (number of months between diagnosis and death caused by the disease. There were no correlation between IDC and DCIS (p = 0.559 regarding β1 integrin expression. Conclusions Considering that the expression of β1 integrin in breast cancer remains controversial, specially its relation with survival of patients, our findings provide further evidence that β1 integrin can be a marker of poor prognosis in breast cancer. Virtual slides The virtual slide(s for this article can be found here: http

  19. Modulation of radiation-induced oral mucositis (mouse) by selective inhibition of β1 integrin

    Introduction: Oral mucositis is a severe side effect of radio(chemo)therapy for head and neck tumors, for which β1 integrins have been proposed as potential therapeutic targets. The present study was initiated to determine the effect of selective inhibition of β1 integrin on the oral epithelial radiation response. Materials and methods: Daily fractionated irradiation was given with 5 × 3 Gy/week over 1 or 2 weeks with/without the β1 integrin-inhibiting monoclonal antibody AIIB2 or an IgG control. Each protocol was terminated by graded test doses to generate full dose–effect curves for mucosal ulceration. The same technique was used for single dose irradiation. Results: Combined single dose irradiation plus AIIB2 resulted in a significant decrease of the ED50 compared to irradiation alone or control IgG. No effect of AIIB2 was found with fractionated irradiation over 1 week. With 2 weeks of fractionation, AIIB2 induced a significant increase in the ED50 for the terminating test irradiation when administered in week 2. The time course of the response was largely unaffected by β1 integrin inhibition. Conclusions: A reduction of mucosal reactions by β1 integrin inhibition later in a course of fractionation was observed, i.e. when epithelial repopulation processes were active. Further mechanistic studies are required.

  20. Discoidin domain receptor 1 is activated independently of beta(1) integrin

    Vogel, W; Brakebusch, C; Fässler, R;

    2000-01-01

    Various types of collagen have been identified as potential ligands for the two mammalian discoidin domain receptor (DDR) tyrosine kinases, DDR1 and DDR2. It is presently unclear whether collagen-induced DDR receptor activation, which occurs with very slow kinetics, involves additional proteins...... blocking antibodies for alpha(2)beta(1) integrin or in cells with a targeted deletion of the beta(1) integrin gene. Finally, we show that overexpression of dominant negative DDR1 in the myoblast cell line C2C12 blocks cellular differentiation and the formation of myofibers....

  1. Beta1 integrin promotes but is not essential for metastasis of ras-myc transformed fibroblasts

    Brakebusch, C; Wennerberg, K; Krell, H W; Weidle, U H; Sallmyr, A; Johansson, S; Fässler, R

    1999-01-01

    integrin-expressing sublines. Tumors were induced by subcutaneous injection of GERM 11 cells and 3 independent beta1 integrin expressing sublines (GERM 116, 1A10, 2F2) into syngeneic mice. After 10 days tumors were surgically removed. While average weights of GERM 11 and GERM 116 tumors were similar...

  2. ADAM12 and alpha9beta1 integrin are instrumental in human myogenic cell differentiation

    Lafuste, Peggy; Sonnet, Corinne; Chazaud, Bénédicte; Dreyfus, Patrick A; Gherardi, Romain K; Wewer, Ulla M; Authier, François-Jérôme

    2005-01-01

    of alpha9 parallels that of ADAM12 and culminates at time of fusion. alpha9 and ADAM12 coimmunoprecipitate and participate to mpc adhesion. Inhibition of ADAM12/alpha9beta1 integrin interplay, by either ADAM12 antisense oligonucleotides or blocking antibody to alpha9beta1, inhibited overall mpc...

  3. CD46 and beta1 integrin relocation in the sperm head during capacitation and acrosome reaction

    Šebková, N.; Frolíková, M.; Dvořáková-Hortová, Kateřina

    Madison: Society for the Study of Reproduction, 2015. s. 212. [48th Annual Meeting of the Society for the Study of reproduction. 18.06.2015-22.06.2015, San Juan] R&D Projects: GA ČR(CZ) GA14-05547S Institutional support: RVO:86652036 Keywords : CD46 * beta1 integrin * Proximity Ligation Assay * acrosome reaction Subject RIV: CE - Biochemistry

  4. Tissue inhibitor of metalloproteinase-2 (TIMP-2) regulates myogenesis and β1 integrin expression in vitro

    Myogenesis in vitro involves myoblast cell cycle arrest, migration, and fusion to form multinucleated myotubes. Extracellular matrix (ECM) integrity during these processes is maintained by the opposing actions of matrix metalloproteinase (MMP) proteases and their inhibitors, the tissue inhibitor of metalloproteinases (TIMPs). Here, we report that TIMP-2, MMP-2, and MT1-MMP are differentially expressed during mouse myoblast differentiation in vitro. A specific role for TIMP-2 in myogenesis is demonstrated by altered TIMP-2-/- myotube formation. When differentiated in horse serum-containing medium, TIMP-2-/- myotubes are larger than wild-type myotubes. In contrast, when serum-free medium is used, TIMP-2-/- myotubes are smaller than wild-type myotubes. Regardless of culture condition, myotube size is directly correlated with MMP activity and inversely correlated with β1 integrin expression. Treatment with recombinant TIMP-2 rescues reduced TIMP-2-/- myotube size and induces increased MMP-9 activation and decreased β1 integrin expression. Treatment with either MMP-2 or MMP-9 similarly rescues reduced myotube size, but has no effect on β1 integrin expression. These data suggest a specific regulatory relationship between TIMP-2 and β1 integrin during myogenesis. Elucidating the role of TIMP-2 in myogenesis in vitro may lead to new therapeutic options for the use of TIMP-2 in myopathies and muscular dystrophies in vivo

  5. Beta1 integrins differentially control extravasation of inflammatory cell subsets into the CNS during autoimmunity

    Bauer, Martina; Brakebusch, Cord; Coisne, Caroline;

    2009-01-01

    )-integrin gene either in all hematopoietic cells or selectively in T lymphocytes. Our results show that T cells critically rely on beta(1) integrins to accumulate in the central nervous system (CNS) during EAE, whereas CNS infiltration of beta(1)-deficient myeloid cells remains unaffected, suggesting that T...

  6. Interaction between fibronectin and β1 integrin is essential for tooth development.

    Kan Saito

    Full Text Available The dental epithelium and extracellular matrix interact to ensure that cell growth and differentiation lead to the formation of teeth of appropriate size and quality. To determine the role of fibronectin in differentiation of the dental epithelium and tooth formation, we analyzed its expression in developing incisors. Fibronectin mRNA was expressed during the presecretory stage in developing dental epithelium, decreased in the secretory and early maturation stages, and then reappeared during the late maturation stage. The binding of dental epithelial cells derived from postnatal day-1 molars to a fibronectin-coated dish was inhibited by the RGD but not RAD peptide, and by a β1 integrin-neutralizing antibody, suggesting that fibronectin-β1 integrin interactions contribute to dental epithelial-cell binding. Because fibronectin and β1 integrin are highly expressed in the dental mesenchyme, it is difficult to determine precisely how their interactions influence dental epithelial differentiation in vivo. Therefore, we analyzed β1 integrin conditional knockout mice (Intβ1lox-/lox-/K14-Cre and found that they exhibited partial enamel hypoplasia, and delayed eruption of molars and differentiation of ameloblasts, but not of odontoblasts. Furthermore, a cyst-like structure was observed during late ameloblast maturation. Dental epithelial cells from knockout mice did not bind to fibronectin, and induction of ameloblastin expression in these cells by neurotrophic factor-4 was inhibited by treatment with RGD peptide or a fibronectin siRNA, suggesting that the epithelial interaction between fibronectin and β1 integrin is important for ameloblast differentiation and enamel formation.

  7. Signaling through urokinase and urokinase receptor in lung cancer cells requires interactions with beta1 integrins.

    Tang, Chi-Hui; Hill, Marla L; Brumwell, Alexis N; Chapman, Harold A; Wei, Ying

    2008-11-15

    The urokinase receptor (uPAR) is upregulated upon tumor cell invasion and correlates with poor lung cancer survival. Although a cis-interaction with integrins has been ascribed to uPAR, whether this interaction alone is critical to urokinase (uPA)- and uPAR-dependent signaling and tumor promotion is unclear. Here we report the functional consequences of point mutations of uPAR (H249A-D262A) that eliminate beta1 integrin interactions but maintain uPA binding, vitronectin attachment and association with alphaV integrins, caveolin and epidermal growth factor receptor. Disruption of uPAR interactions with beta1 integrins recapitulated previously reported findings with beta1-integrin-derived peptides that attenuated matrix-dependent ERK activation, MMP expression and in vitro migration by human lung adenocarcinoma cell lines. The uPAR mutant cells acquired enhanced capacity to adhere to vitronectin via uPAR-alphaVbeta5-integrin, rather than through the uPAR-alpha3beta1-integrin complex and they were unable to initiate uPA signaling to activate ERK, Akt or Stat1. In an orthotopic lung cancer model, uPAR mutant cells exhibited reduced tumor size compared with cells expressing wild-type uPAR. Taken together, the results indicate that uPAR-beta1-integrin interactions are essential to signals induced by integrin matrix ligands or uPA that support lung cancer cell invasion in vitro and progression in vivo. PMID:18940913

  8. beta1-integrin-mediated signaling essentially contributes to cell survival after radiation-induced genotoxic injury

    Cordes, N; Seidler, J; Durzok, R; Geinitz, H; Brakebusch, C

    2006-01-01

    Integrin-mediated adhesion to extracellular matrix proteins confers resistance to radiation- or drug-induced genotoxic injury. To analyse the underlying mechanisms specific for beta1-integrins, wild-type beta1A-integrin-expressing GD25beta1A cells were compared to GD25beta1B cells, which express...... findings in tumor cells, human A-172 glioma cells were examined under the same conditions after siRNA-mediated silencing of beta1-integrins. We found that beta1A-integrin-mediated adhesion to fibronectin, collagen-III or beta1-IgG was essential for cell survival after radiation-induced genotoxic injury...... central role of beta1-integrins in Akt- and p130Cas/paxillin-mediated prosurvival signaling. These findings suggest beta1-integrins as critical regulators of cell survival after radiation-induced genotoxic injury. Elucidation of the molecular circuitry of prosurvival beta1-integrin-mediated signaling in...

  9. Bidirectional remodeling of β1-integrin adhesions during chemotropic regulation of nerve growth

    Carlstrom Lucas P

    2011-11-01

    Full Text Available Abstract Background Chemotropic factors in the extracellular microenvironment guide nerve growth by acting on the growth cone located at the tip of extending axons. Growth cone extension requires the coordination of cytoskeleton-dependent membrane protrusion and dynamic adhesion to the extracellular matrix, yet how chemotropic factors regulate these events remains an outstanding question. We demonstrated previously that the inhibitory factor myelin-associated glycoprotein (MAG triggers endocytic removal of the adhesion receptor β1-integrin from the growth cone surface membrane to negatively remodel substrate adhesions during chemorepulsion. Here, we tested how a neurotrophin might affect integrin adhesions. Results We report that brain-derived neurotropic factor (BDNF positively regulates the formation of substrate adhesions in axonal growth cones during stimulated outgrowth and prevents removal of β1-integrin adhesions by MAG. Treatment of Xenopus spinal neurons with BDNF rapidly triggered β1-integrin clustering and induced the dynamic formation of nascent vinculin-containing adhesion complexes in the growth cone periphery. Both the formation of nascent β1-integrin adhesions and the stimulation of axon extension by BDNF required cytoplasmic calcium ion signaling and integrin activation at the cell surface. Exposure to MAG decreased the number of β1-integrin adhesions in the growth cone during inhibition of axon extension. In contrast, the BDNF-induced adhesions were resistant to negative remodeling by MAG, correlating with the ability of BDNF pretreatment to counteract MAG-inhibition of axon extension. Pre-exposure to MAG prevented the BDNF-induced formation of β1-integrin adhesions and blocked the stimulation of axon extension by BDNF. Conclusions Altogether, these findings demonstrate the neurotrophin-dependent formation of integrin-based adhesions in the growth cone and reveal how a positive regulator of substrate adhesions can block

  10. Loss of β1-integrin from urothelium results in overactive bladder and incontinence in mice: a mechanosensory rather than structural phenotype

    Kanasaki, Keizo; Yu, Weiqun; von Bodungen, Maximilian; Larigakis, John D.; Kanasaki, Megumi; Ayala de la Pena, Francisco; Kalluri, Raghu; Hill, Warren G.

    2013-01-01

    Bladder urothelium senses and communicates information about bladder fullness. However, the mechanoreceptors that respond to tissue stretch are poorly defined. Integrins are mechanotransducers in other tissues. Therefore, we eliminated β1-integrin selectively in urothelium of mice using Cre-LoxP targeted gene deletion. β1-Integrin localized to basal/intermediate urothelial cells by confocal microscopy. β1-Integrin conditional-knockout (β1-cKO) mice lacking urothelial β1-integrin exhibited dow...

  11. Fetal and adult hematopoietic stem cells require beta1 integrin function for colonizing fetal liver, spleen, and bone marrow

    Potocnik, A J; Brakebusch, C; Fässler, R

    2000-01-01

    Homing of hematopoietic stem cells (HSCs) into hematopoietic organs is a prerequisite for the establishment of hematopoiesis during embryogenesis and after bone marrow transplantation. We show that beta1 integrin-deficient HSCs from the para-aortic splanchnopleura and the fetal blood had hematoly......Homing of hematopoietic stem cells (HSCs) into hematopoietic organs is a prerequisite for the establishment of hematopoiesis during embryogenesis and after bone marrow transplantation. We show that beta1 integrin-deficient HSCs from the para-aortic splanchnopleura and the fetal blood had...... hematolymphoid differentiation potential in vitro and in fetal organ cultures but were unable to seed fetal and adult hematopoietic tissues. Adult beta1 integrin null HSCs isolated from mice carrying loxP-tagged beta1 integrin alleles and ablated for beta1 integrin expression by retroviral cre transduction...... failed to engraft irradiated recipient mice. Moreover, absence of beta1 integrin resulted in sequestration of HSCs in the circulation and their reduced adhesion to endothelioma cells. These findings define beta1 integrin as an essential adhesion receptor for the homing of HSCs....

  12. Dystrophin Dp71f associates with the beta1-integrin adhesion complex to modulate PC12 cell adhesion

    Cerna, Joel; Cerecedo, Doris; Ortega, Arturo; García-Sierra, Francisco; Centeno, Federico; Garrido, Efrain; Mornet, Dominique; Cisneros, Bulmaro

    2006-01-01

    Dystrophin Dp71 is the main product of the Duchenne muscular dystrophy gene in the brain; however, its function is unknown. To study the role of Dp71 in neuronal cells, we previously generated by antisense treatment PC12 neuronal cell clones with decreased Dp71 expression (antisense-Dp71 cells). PC12 cells express two different splicing isoforms of Dp71, a cytoplasmic variant called Dp71f and a nuclear isoform called Dp71d. We previously reported that antisense-Dp71 cells display deficient adhesion to substrate and reduced immunostaining of β1-integrin in the cell area contacting the substrate. In this study, we isolated additional antisenseDp71 clones to analyze in detail the potential involvement of Dp71f isoform with the β1-integrin adhesion system of PC12 cells. Immunofluorescence analyses as well as immunoprecipitation assays demonstrated that the PC12 cell β1-integrin adhesion complex is composed of β1-integrin, talin, paxillin, α-actinin, FAK and actin. In addition, our results showed that Dp71f associates with most of the β1-integrin complex components (β1-integrin, FAK, α-actinin, talin and actin). In the antisense-Dp71 cells, the deficiency of Dp71 provokes a significant reduction of the β1-integrin adhesion complex and, consequently, the deficient adhesion of these cells to laminin. In vitro binding experiments confirmed the interaction of Dp71f with FAK and β1-integrin. Our data indicate that Dp71f is a structural component of the β1-integrin adhesion complex of PC12 cells that modulates PC12 cell adhesion by conferring proper complex assembly and/or maintenance. PMID:16935300

  13. Alpha9beta1 integrin in melanoma cells can signal different adhesion states for migration and anchorage

    Lydolph, Magnus C; Morgan-Fisher, Marie; Høye, Anette M;

    2009-01-01

    Cell surface integrins are the primary receptors for cell migration on extracellular matrix, and exist in several activation states regulated in part by ectodomain conformation. The alpha9 integrin subunit, which pairs only with beta1, has specific roles in the immune system and may regulate cell......beta1 integrin- and Rho kinase-dependent focal adhesion and stress fibre formation, suggesting that the activation status of alpha9beta1 integrin was altered. The effect of manganese ions in promoting focal adhesion formation was reproduced by beta1 integrin activating antibody. The alpha9beta1...

  14. beta 1 integrin inhibition dramatically enhances radiotherapy efficacy in human breast cancer xenografts

    Park, Catherine C.; Park, Catherine C.; Zhang, Hui J.; Yao, Evelyn S.; Park, Chong J.; Bissell, Mina J.

    2008-06-02

    {beta}1 integrin signaling has been shown to mediate cellular resistance to apoptosis after exposure to ionizing radiation (IR). Other signaling molecules that increase resistance include Akt, which promotes cell survival downstream of {beta}1 integrin signaling. We showed previously that {beta}1 integrin inhibitory antibodies, AIIB2, enhance apoptosis and decrease growth in human breast cancer cells in 3 dimensional laminin-rich extracellular matrix (3D lrECM) cultures and in vivo. Here we asked whether AIIB2 could synergize with IR to modify Akt-mediated IR resistance. We used 3D lrECM cultures to test the optimal combination of AIIB2 with IR treatment of two breast cancer cell lines, MCF-7 and HMT3522-T4-2, as well as T4-2 myr-Akt breast cancer colonies or HMT3522-S-1, which form normal organotypic structures in 3D lrECM. Colonies were assayed for apoptosis and {beta}1 integrin/Akt signaling pathways were evaluated using western blot. In addition, mice bearing MCF-7 xenografts were used to validate the findings in 3D lrECM. We report that AIIB2 increased apoptosis optimally post-IR by down regulating Akt in breast cancer colonies in 3D lrECM. In vivo, addition of AIIB2 after IR significantly enhanced tumor growth inhibition and apoptosis compared to either treatment alone. Remarkably, the degree of tumor growth inhibition using AIIB2 plus 2 Gy radiation was similar to that of 8 Gy alone. We showed previously that AIIB2 had no discernible toxicity in mice; here, its addition allowed for a significant reduction in the IR dose that was necessary to achieve comparable growth inhibition and apoptosis in breast cancer xenografts in vivo.

  15. PRG-1 Regulates Synaptic Plasticity via Intracellular PP2A/β1-Integrin Signaling.

    Liu, Xingfeng; Huai, Jisen; Endle, Heiko; Schlüter, Leslie; Fan, Wei; Li, Yunbo; Richers, Sebastian; Yurugi, Hajime; Rajalingam, Krishnaraj; Ji, Haichao; Cheng, Hong; Rister, Benjamin; Horta, Guilherme; Baumgart, Jan; Berger, Hendrik; Laube, Gregor; Schmitt, Ulrich; Schmeisser, Michael J; Boeckers, Tobias M; Tenzer, Stefan; Vlachos, Andreas; Deller, Thomas; Nitsch, Robert; Vogt, Johannes

    2016-08-01

    Alterations in dendritic spine numbers are linked to deficits in learning and memory. While we previously revealed that postsynaptic plasticity-related gene 1 (PRG-1) controls lysophosphatidic acid (LPA) signaling at glutamatergic synapses via presynaptic LPA receptors, we now show that PRG-1 also affects spine density and synaptic plasticity in a cell-autonomous fashion via protein phosphatase 2A (PP2A)/β1-integrin activation. PRG-1 deficiency reduces spine numbers and β1-integrin activation, alters long-term potentiation (LTP), and impairs spatial memory. The intracellular PRG-1 C terminus interacts in an LPA-dependent fashion with PP2A, thus modulating its phosphatase activity at the postsynaptic density. This results in recruitment of adhesome components src, paxillin, and talin to lipid rafts and ultimately in activation of β1-integrins. Consistent with these findings, activation of PP2A with FTY720 rescues defects in spine density and LTP of PRG-1-deficient animals. These results disclose a mechanism by which bioactive lipid signaling via PRG-1 could affect synaptic plasticity and memory formation. PMID:27453502

  16. Conditional beta1-integrin gene deletion in neural crest cells causes severe developmental alterations of the peripheral nervous system

    Pietri, Thomas; Eder, Olivier; Breau, Marie Anne;

    2004-01-01

    Integrins are transmembrane receptors that are known to interact with the extracellular matrix and to be required for migration, proliferation, differentiation and apoptosis. We have generated mice with a neural crest cell-specific deletion of the beta1-integrin gene to analyse the role of beta1-...... almost complete absence of Schwann cells and sensory axon segregation and defective maturation in neuromuscular synaptogenesis. Thus, beta1-integrins are important for the control of embryonic and postnatal peripheral nervous system development....

  17. A preliminary optical and electron microscopic study of the beta(1) integrin distribution pattern of human osteosarcoma-derived cells.

    Banai, Kiarash; Brady, Ken; McDonald, Fraser

    2004-07-01

    Immunogold labelling was used to study the organisation of the beta(1) integrins on osteosarcoma-derived osteoblasts (Saos-2 and MG-63). Monolayers of cells were prepared in multiwell culture plates on both uncovered and collagen-covered coverslips, and beta(1) integrins were primarily labelled using mouse monoclonal antibodies to beta(1) integrins. Indirect immunofluorescence labels using an anti-mouse fluorescein-conjugated goat antibody showed an even distribution of the beta(1) integrins on the cell membranes of all cell types used. A concentration of 2 microg/ml of the primary antibodies and a 1:100 dilution of the secondary antibodies were determined as the optimal concentration for labelling to use with indirect localisation of the primary antibodies gold conjugated to goat anti-mouse antibodies and viewed under an electron microscope. Ten nanometre gold particles were used for transmission electron microscopy (TEM) and 40 nm gold particles for scanning electron microscopy. TEM showed that beta(1) integrins were mainly clustered on the cell membrane processes with less labelling on the cell membranes themselves. The distribution of beta(1) integrins on osteosarcoma cells supports the concept that integrins may function by forming focal adhesions at the site of the cytoplasmic membrane processes. PMID:15241608

  18. Highly Potent, Water Soluble Benzimidazole Antagonist for Activated (alpha)4(beta)1 Integrin

    Carpenter, R D; Andrei, M; Lau, E Y; Lightstone, F C; Liu, R; Lam, K S; Kurth, M J

    2007-08-29

    The cell surface receptor {alpha}{sub 4}{beta}{sub 1} integrin, activated constitutively in lymphoma, can be targeted with the bisaryl urea peptidomimetic antagonist 1 (LLP2A). However, concerns on its preliminary pharmacokinetic (PK) profile provided an impetus to change the pharmacophore from a bisaryl urea to a 2-arylaminobenzimidazole moiety resulting in improved solubility while maintaining picomolar potency [5 (KLCA4); IC{sub 50} = 305 pM]. With exceptional solubility, this finding has potential for improving PK to help diagnose and treat lymphomas.

  19. Skin and hair follicle integrity is crucially dependent on beta 1 integrin expression on keratinocytes

    Brakebusch, C; Grose, R; Quondamatteo, F;

    2000-01-01

    developed severe hair loss due to a reduced proliferation of hair matrix cells and severe hair follicle abnormalities. Eventually, the malformed hair follicles were removed by infiltrating macrophages. The epidermis of the back skin became hyperthickened, the basal keratinocytes showed reduced expression of......, the integrity of the basement membrane surrounding the beta 1-deficient hair follicle was not affected. Finally, the dermis became fibrotic. These results demonstrate an important role of beta 1 integrins in hair follicle morphogenesis, in the processing of basement membrane components, in the...

  20. Evaluation of β1-integrin expression on chondrogenically differentiating human adipose-derived stem cells using atomic force microscopy.

    Quisenberry, Chrystal R; Nazempour, Arshan; Van Wie, Bernard J; Abu-Lail, Nehal I

    2016-06-01

    The expression of β1-integrin on human adipose-derived stem cells, differentiating toward a chondrogenic lineage, is hypothesized to decrease when cells are grown under in vivo-like environments due to sufficient extracellular matrix (ECM) buildup in the engineered tissues. The opposite is true when cells are grown in static cultures such as in pellet or micromass. To probe β1-integrin distribution on cellular surfaces, atomic force microscopy cantilevers modified with anti-β1-integrin antibodies were used. Specific antibody-antigen adhesion forces were identified and indicated the locations of β1-integrins on cells. ECM properties were assessed by estimating the Young's modulus of the matrix. Specific single antibody-antigen interactions averaged 78 ± 10 pN with multiple bindings occurring at approximate multiples of 78 pN. The author's results show that upregulated β1-integrin expression coincided with a less robust ECM as assessed by mechanical properties of tissues. In micromass and pellet cultures, transforming growth factor β3(TGF-β3) elicited a decrease in Young's modulus by 3.7- and 4.4-fold while eliciting an increase in β1-integrin count by 1.1- and 1.3-fold, respectively. β1-integrin counts on cells grown in the presence of TGF-β3 with oscillating hydrostatic pressure decreased by a 1.1-fold while the Young's modulus increased by a 1.9-fold. Collectively, our results suggest that cells in insufficiently robust ECM express more integrin perhaps to facilitate cell-ECM adhesion and compensate for a looser less robust ECM. PMID:27106564

  1. Tumor cell adhesion to endothelial cells is increased by endotoxin via an upregulation of beta-1 integrin expression.

    Andrews, E J

    2012-02-03

    BACKGROUND: Recent studies have demonstrated that metastatic disease develops from tumor cells that adhere to endothelial cells and proliferate intravascularly. The beta-1 integrin family and its ligand laminin have been shown to be important in tumor-to-endothelial cell adhesion. Lipopolysaccharide (LPS) has been implicated in the increased metastatic tumor growth that is seen postoperatively. We postulated that LPS increases tumor cell expression of beta-1 integrins and that this leads to increased adhesion. METHODS: The human metastatic colon cancer cell line LS174T was labeled with an enhanced green fluorescent protein (eGFP) using retroviral transfection. Cell cultures were treated with LPS for 1, 2, and 4 h (n = 6 each) and were subsequently cocultured for 30 or 120 min with confluent human umbilical vein endothelial cells (HUVECs), to allow adherence. Adherent tumor cells were counted using fluorescence microscopy. These experiments were carried out in the presence or absence of a functional blocking beta-1 integrin monoclonal antibody (4B4). Expression of beta-1 integrin and laminin on tumor and HUVECs was assessed using flow cytometric analysis. Tumor cell NF-kappaB activation after incubation with LPS was measured. RESULTS: Tumor cell and HUVEC beta-1 integrin expression and HUVEC expression of laminin were significantly (P < 0.05) enhanced after incubation with LPS. Tumor cell adhesion to HUVECs was significantly increased. Addition of the beta-1 integrin blocking antibody reduced tumor cell adhesion to control levels. LPS increased tumor cell NF-kappaB activation. CONCLUSIONS: Exposure to LPS increases tumor cell adhesion to the endothelium through a beta-1 integrin-mediated pathway that is NF-kappaB dependent. This may provide a target for immunotherapy directed at reducing postoperative metastatic tumor growth.

  2. LFA-1 and Mac-1 integrins bind to the serine/threonine-rich domain of thrombomodulin.

    Kawamoto, Eiji; Okamoto, Takayuki; Takagi, Yoshimi; Honda, Goichi; Suzuki, Koji; Imai, Hiroshi; Shimaoka, Motomu

    2016-05-13

    LFA-1 (αLβ2) and Mac-1 (αMβ2) integrins regulate leukocyte trafficking in health and disease by binding primarily to IgSF ligand ICAM-1 and ICAM-2 on endothelial cells. Here we have shown that the anti-coagulant molecule thrombomodulin (TM), found on the surface of endothelial cells, functions as a potentially new ligand for leukocyte integrins. We generated a recombinant extracellular domain of human TM and Fc fusion protein (TM-domains 123-Fc), and showed that pheripheral blood mononuclear cells (PBMCs) bind to TM-domains 123-Fc dependent upon integrin activation. We then demonstrated that αL integrin-blocking mAb, αM integrin-blocking mAb, and β2 integrin-blocking mAb inhibited the binding of PBMCs to TM-domains 123-Fc. Furthermore, we show that the serine/threonine-rich domain (domain 3) of TM is required for the interaction with the LFA-1 (αLβ2) and Mac-1 (αMβ2) integrins to occur on PBMCs. These results demonstrate that the LFA-1 and Mac-1 integrins on leukocytes bind to TM, thereby establishing the molecular and structural basis underlying LFA-1 and Mac-1 integrin interaction with TM on endothelial cells. In fact, integrin-TM interactions might be involved in the dynamic regulation of leukocyte adhesion with endothelial cells. PMID:27055590

  3. Vesicle-associated membrane protein 2 mediates trafficking of α5β1 integrin to the plasma membrane

    Integrins are major receptors for cell adhesion to the extracellular matrix (ECM). As transmembrane proteins, the levels of integrins at the plasma membrane or the cell surface are ultimately determined by the balance between two vesicle trafficking events: endocytosis of integrins at the plasma membrane and exocytosis of the vesicles that transport integrins. Here, we report that vesicle-associated membrane protein 2 (VAMP2), a SNARE protein that mediates vesicle fusion with the plasma membrane, is involved in the trafficking of α5β1 integrin. VAMP2 was present on vesicles containing endocytosed β1 integrin. Small interfering RNA (siRNA) silencing of VAMP2 markedly reduced cell surface α5β1 and inhibited cell adhesion and chemotactic migration to fibronectin, the ECM ligand of α5β1, without altering cell surface expression of α2β1 integrin or α3β1 integrin. By contrast, silencing of VAMP8, another SNARE protein, had no effect on cell surface expression of the integrins or cell adhesion to fibronectin. In addition, VAMP2-mediated trafficking is involved in cell adhesion to collagen but not to laminin. Consistent with disruption of integrin functions in cell proliferation and survival, VAMP2 silencing diminished proliferation and triggered apoptosis. Collectively, these data indicate that VAMP2 mediates the trafficking of α5β1 integrin to the plasma membrane and VAMP2-dependent integrin trafficking is critical in cell adhesion, migration and survival.

  4. alpha 11beta 1 integrin recognizes the GFOGER sequence in interstitial collagens.

    Zhang, Wan-Ming; Kapyla, Jarmo; Puranen, J Santeri; Knight, C Graham; Tiger, Carl-Fredrik; Pentikainen, Olli T; Johnson, Mark S; Farndale, Richard W; Heino, Jyrki; Gullberg, Donald

    2003-02-28

    The integrins alpha(1)beta(1), alpha(2)beta(1), alpha(10)beta(1), and alpha(11)beta(1) are referred to as a collagen receptor subgroup of the integrin family. Recently, both alpha(1)beta(1) and alpha(2)beta(1) integrins have been shown to recognize triple-helical GFOGER (where single letter amino acid nomenclature is used, O = hydroxyproline) or GFOGER-like motifs found in collagens, despite their distinct binding specificity for various collagen subtypes. In the present study we have investigated the mechanism whereby the latest member in the integrin family, alpha(11)beta(1), recognizes collagens using C2C12 cells transfected with alpha(11) cDNA and the bacterially expressed recombinant alpha(11) I domain. The ligand binding properties of alpha(11)beta(1) were compared with those of alpha(2)beta(1). Mg(2+)-dependent alpha(11)beta(1) binding to type I collagen required micromolar Ca(2+) but was inhibited by 1 mm Ca(2+), whereas alpha(2)beta(1)-mediated binding was refractory to millimolar concentrations of Ca(2+). The bacterially expressed recombinant alpha(11) I domain preference for fibrillar collagens over collagens IV and VI was the same as the alpha(2) I domain. Despite the difference in Ca(2+) sensitivity, alpha(11)beta(1)-expressing cells and the alpha(11) I domain bound to helical GFOGER sequences in a manner similar to alpha(2)beta(1)-expressing cells and the alpha(2) I domain. Modeling of the alpha I domain-collagen peptide complexes could partially explain the observed preference of different I domains for certain GFOGER sequence variations. In summary, our data indicate that the GFOGER sequence in fibrillar collagens is a common recognition motif used by alpha(1)beta(1), alpha(2)beta(1), and also alpha(11)beta(1) integrins. Although alpha(10) and alpha(11) chains show the highest sequence identity, alpha(2) and alpha(11) are more similar with regard to collagen specificity. Future studies will reveal whether alpha(2)beta(1) and alpha(11)beta(1

  5. Lack of beta1 integrins in enteric neural crest cells leads to a Hirschsprung-like phenotype

    Breau, Marie A; Pietri, Thomas; Eder, Olivier;

    2006-01-01

    The enteric nervous system arises mainly from vagal and sacral neural crest cells that colonise the gut between 9.5 and 14 days of development in mice. Using the Cre-LoxP system, we removed beta1 integrins in the neural crest cells when they emerge from the neural tube. beta1-null enteric neural...... integrins are required for the villi innervation in the small intestine. Our findings highlight the crucial roles played by beta1 integrins at various steps of enteric nervous system development....

  6. HGF Accelerates Wound Healing by Promoting the Dedifferentiation of Epidermal Cells through β1-Integrin/ILK Pathway

    Jin-Feng Li

    2013-01-01

    Full Text Available Skin wound healing is a critical and complex biological process after trauma. This process is activated by signaling pathways of both epithelial and nonepithelial cells, which release a myriad of different cytokines and growth factors. Hepatocyte growth factor (HGF is a cytokine known to play multiple roles during the various stages of wound healing. This study evaluated the benefits of HGF on reepithelialization during wound healing and investigated its mechanisms of action. Gross and histological results showed that HGF significantly accelerated reepithelialization in diabetic (DB rats. HGF increased the expressions of the cell adhesion molecules β1-integrin and the cytoskeleton remodeling protein integrin-linked kinase (ILK in epidermal cells in vivo and in vitro. Silencing of ILK gene expression by RNA interference reduced expression of β1-integrin, ILK, and c-met in epidermal cells, concomitantly decreasing the proliferation and migration ability of epidermal cells. β1-Integrin can be an important maker of poorly differentiated epidermal cells. Therefore, these data demonstrate that epidermal cells become poorly differentiated state and regained some characteristics of epidermal stem cells under the role of HGF after wound. Taken together, the results provide evidence that HGF can accelerate reepithelialization in skin wound healing by dedifferentiation of epidermal cells in a manner related to the β1-integrin/ILK pathway.

  7. α-Hemolysin enhances Staphylococcus aureus internalization and survival within mast cells by modulating the expression of β1 integrin.

    Goldmann, Oliver; Tuchscherr, Lorena; Rohde, Manfred; Medina, Eva

    2016-06-01

    Mast cells (MCs) are important sentinels of the host defence against invading pathogens. We previously reported that Staphylococcus aureus evaded the extracellular antimicrobial activities of MCs by promoting its internalization within these cells via β1 integrins. Here, we investigated the molecular mechanisms governing this process. We found that S. aureus responded to the antimicrobial mediators released by MCs by up-regulating the expression of α-hemolysin (Hla), fibronectin-binding protein A and several regulatory systems. We also found that S. aureus induced the up-regulation of β1 integrin expression on MCs and that this effect was mediated by Hla-ADAM10 (a disintegrin and metalloproteinase 10) interaction. Thus, deletion of Hla or inhibition of Hla-ADAM10 interaction significantly impaired S. aureus internalization within MCs. Furthermore, purified Hla but not the inactive HlaH35L induced up-regulation of β1 integrin expression in MCs in a dose-dependent manner. Our data support a model in which S. aureus counter-reacts the extracellular microbicidal mechanisms of MCs by increasing expression of fibronectin-binding proteins and by inducing Hla-ADAM10-mediated up-regulation of β1 integrin in MCs. The up-regulation of bacterial fibronectin-binding proteins, concomitantly with the increased expression of its receptor β1 integrin on the MCs, resulted in enhanced S. aureus internalization through the binding of fibronectin-binding proteins to integrin β1 via fibronectin. PMID:26595647

  8. Vipegitide: a folded peptidomimetic partial antagonist of α2β1 integrin with antiplatelet aggregation activity

    Momic T

    2015-01-01

    Full Text Available Tatjana Momic,1 Jehoshua Katzhendler,1 Ela Shai,2 Efrat Noy,3 Hanoch Senderowitz,3 Johannes A Eble,4 Cezary Marcinkiewicz,5 David Varon,2 Philip Lazarovici11School of Pharmacy Institute for Drug Research, Faculty of Medicine, The Hebrew University of Jerusalem, 2Department of Hematology, Coagulation Unit, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; 3Department of Chemistry, Bar-Ilan University, Ramat-Gan, Israel; 4Institute for Physiological Chemistry and Pathobiochemistry, University of Münster, Münster, Germany; 5Department of Bioengineering, College of Engineering, Temple University, Philadelphia, PA, USAAbstract: Linear peptides containing the sequence WKTSRTSHY were used as lead compounds to synthesize a novel peptidomimetic antagonist of α2β1 integrin, with platelet aggregation-inhibiting activity, named Vipegitide. Vipegitide is a 13-amino acid, folded peptidomimetic molecule, containing two α-aminoisobutyric acid residues at positions 6 and 8 and not stable in human serum. Substitution of glycine and tryptophan residues at positions 1 and 2, respectively, with a unit of two polyethylene glycol (PEG molecules yielded peptidomimetic Vipegitide-PEG2, stable in human serum for over 3 hours. Vipegitide and Vipegitide-PEG2 showed high potency (7×10-10 M and 1.5×10-10 M, respectively and intermediate efficacy (40% and 35%, respectively as well as selectivity toward α2 integrin in inhibition of adhesion of α1/α2 integrin overexpressing cells toward respective collagens. Interaction of both peptidomimetics with extracellular active domain of α2 integrin was confirmed in cell-free binding assay with recombinant α2 A-domain. Integrin α2β1 receptor is found on the platelet membrane and triggers collagen-induced platelet aggregation. Vipegitide and Vipegitide-PEG2 inhibited α2β1 integrin-mediated adhesion of human and murine platelets under the flow condition, by 50%. They efficiently blocked adenosine diphosphate

  9. Beta1 integrin expression by podocytes is required to maintain glomerular structural integrity.

    Pozzi, Ambra; Jarad, George; Moeckel, Gilbert W; Coffa, Sergio; Zhang, Xi; Gewin, Leslie; Eremina, Vera; Hudson, Billy G; Borza, Dorin-Bogdan; Harris, Raymond C; Holzman, Lawrence B; Phillips, Carrie L; Fassler, Reinhard; Quaggin, Susan E; Miner, Jeffrey H; Zent, Roy

    2008-04-15

    Integrins are transmembrane heteromeric receptors that mediate interactions between cells and extracellular matrix (ECM). beta1, the most abundantly expressed integrin subunit, binds at least 12 alpha subunits. beta1 containing integrins are highly expressed in the glomerulus of the kidney; however their role in glomerular morphogenesis and maintenance of glomerular filtration barrier integrity is poorly understood. To study these questions we selectively deleted beta1 integrin in the podocyte by crossing beta1(flox/flox) mice with podocyte specific podocin-cre mice (pod-Cre), which express cre at the time of glomerular capillary formation. We demonstrate that podocyte abnormalities are visualized during glomerulogenesis of the pod-Cre;beta1(flox/flox) mice and proteinuria is present at birth, despite a grossly normal glomerular basement membrane. Following the advent of glomerular filtration there is progressive podocyte loss and the mice develop capillary loop and mesangium degeneration with little evidence of glomerulosclerosis. By 3 weeks of age the mice develop severe end stage renal failure characterized by both tubulointerstitial and glomerular pathology. Thus, expression of beta1 containing integrins by the podocyte is critical for maintaining the structural integrity of the glomerulus. PMID:18328474

  10. Cellular microenvironment controls the nuclear architecture of breast epithelia through β1-integrin.

    Maya-Mendoza, Apolinar; Bartek, Jiri; Jackson, Dean A; Streuli, Charles H

    2016-02-01

    Defects in nuclear architecture occur in a variety of diseases, however the fundamental mechanisms that control the internal structure of nuclei are poorly defined. Here we reveal that the cellular microenvironment has a profound influence on the global internal organization of nuclei in breast epithelia. A 3D microenvironment induces a prolonged but reversible form of cell cycle arrest that features many of the classical markers of cell senescence. This unique form of arrest is dependent on signaling from the external microenvironment through β1-integrins. It is concomitant with alterations in nuclear architecture that characterize the withdrawal from cell proliferation. Unexpectedly, following prolonged cell cycle arrest in 3D, the senescence-like state and associated reprogramming of nuclear architecture are freely reversible on altering the dimensionality of the cellular microenvironment. Breast epithelia can therefore maintain a proliferative plasticity that correlates with nuclear remodelling. However, the changes in nuclear architecture are cell lineage-specific and do not occur in fibroblasts, and moreover they are overcome in breast cancer cells. PMID:26818565

  11. Laminin/β1 integrin signal triggers axon formation by promoting microtubule assembly and stabilization

    Wen-Liang Lei; Shi-Ge Xing; Cai-Yun Deng; Xiang-Chun Ju; Xing-Yu Jiang; Zhen-Ge Luo

    2012-01-01

    Axon specification during neuronal polarization is closely associated with increased microtubule stabilization in one of the neurites of unpolarized neuron,but how this increased microtubule stability is achieved is unclear.Here,we show that extracellular matrix (ECM) component laminin promotes neuronal polarization via regulating directional microtubule assembly through β1 integrin (Itgb1).Contact with laminin coated on culture substrate or polystyrene beads was sufficient for axon specification of undifferentiated neurites in cultured hippocampal neurons and cortical slices.Active Itgb1 was found to be concentrated in laminin-contacting neurites.Axon formation was promoted and abolished by enhancing and attenuating Itgbl signaling,respectively.Interestingly,laminin contact promoted plus-end microtubule assembly in a manner that required Itgbl.Moreover,stabilizing microtubules partially prevented polarization defects caused by ltgbl downregulation.Finally,genetic ablation of ltgbl in dorsal telencephalic progenitors caused deficits in axon development of cortical pyramidal neurons.Thus,laminin/Itgb1 signaling plays an instructive role in axon initiation and growth,both in vitro and in vivo,through the regulation of microtubule assembly.This study has established a linkage between an extrinsic factor and intrinsic cytoskeletai dynamics during neuronal polarization.

  12. Dynamic expression of alpha 1 beta 1 and alpha 2 beta 1 integrin receptors by human vascular smooth muscle cells. Alpha 2 beta 1 integrin is required for chemotaxis across type I collagen-coated membranes.

    Skinner, M P; Raines, E W; Ross, R.

    1994-01-01

    Vascular smooth muscle cells (SMCs) in the media of normal arteries express alpha 1 beta 1 integrin with no detectable alpha 2 beta 1 as determined by immunocytochemistry. In contrast, immunoprecipitation of integrins expressed by human SMCs cultured from medial explants shows strong expression of alpha 2 beta 1 and no expression of alpha 1 beta 1. The apparent reciprocal expression of these two collagen and laminin receptors was confirmed by flow cytometric analysis of fluorescent labeled ce...

  13. Increasing α7β1-integrin promotes muscle cell proliferation, adhesion, and resistance to apoptosis without changing gene expression

    LIU, Jianming; Burkin, Dean J.; Kaufman, Stephen J.

    2007-01-01

    The dystrophin-glycoprotein complex maintains the integrity of skeletal muscle by associating laminin in the extracellular matrix with the actin cytoskeleton. Several human muscular dystrophies arise from defects in the components of this complex. The α7β1-integrin also binds laminin and links the extracellular matrix with the cytoskeleton. Enhancement of α7-integrin levels alleviates pathology in mdx/utrn−/− mice, a model of Duchenne muscular dystrophy, and thus the integrin may functionally...

  14. RECK-Mediated β1-Integrin Regulation by TGF-β1 Is Critical for Wound Contraction in Mice

    Gutiérrez, Jaime; Droppelmann, Cristian A.; Contreras, Osvaldo; Takahashi, Chiaki; Brandan, Enrique

    2015-01-01

    Fibroblasts are critical for wound contraction; a pivotal step in wound healing. They produce and modify the extracellular matrix (ECM) required for the proper tissue remodeling. Reversion-inducing cysteine-rich protein with Kazal motifs (RECK) is a key regulator of ECM homeostasis and turnover. However, its role in wound contraction is presently unknown. Here we describe that Transforming growth factor type β1 (TGF-β1), one of the main pro-fibrotic wound-healing promoting factors, decreases RECK expression in fibroblasts through the Smad and JNK dependent pathways. This TGF-β1 dependent downregulation of RECK occurs with the concomitant increase of β1-integrin, which is required for fibroblasts adhesion and wound contraction through the activation of focal adhesion kinase (FAK). Loss and gain RECK expression experiments performed in different types of fibroblasts indicate that RECK downregulation mediates TGF-β1 dependent β1-integrin expression. Also, reduced levels of RECK potentiate TGF-β1 effects over fibroblasts FAK-dependent contraction, without affecting its cognate signaling. The above results were confirmed on fibroblasts derived from the Reck+/- mice compared to wild type-derived fibroblasts. We observed that Reck+/- mice heal dermal wounds more efficiently than wild type mice. Our results reveal a critical role for RECK in skin wound contraction as a key mediator in the axis: TGF-β1—RECK- β1-integrin. PMID:26247610

  15. Mechanotransduction molecules in the plant gravisensory response: amyloplast/statolith membranes contain a beta 1 integrin-like protein

    Lynch, T. M.; Lintilhac, P. M.; Domozych, D.

    1998-01-01

    It has been hypothesized that the sedimentation of amyloplasts within root cap cells is the primary event in the plant gravisensory-signal transduction cascade. Statolith sedimentation, with its ability to generate weighty mechanical signals, is a legitimate means for organisms to discriminate the direction of the gravity vector. However, it has been demonstrated that starchless mutants with reduced statolith densities maintain some ability to sense gravity, calling into question the statolith sedimentation hypothesis. Here we report on the presence of a beta 1 integrin-like protein localized inside amyloplasts of tobacco NT-1 suspension culture, callus cells, and whole-root caps. Two different antibodies to the beta 1 integrin, one to the cytoplasmic domain and one to the extracellular domain, localize in the vicinity of the starch grains within amyloplasts of NT-1. Biochemical data reveals a 110-kDa protein immunoprecipitated from membrane fractions of NT-1 suspension culture indicating size homology to known beta 1 integrin in animals. This study provides the first direct evidence for the possibility of integrin-mediated signal transduction in the perception of gravity by higher plants. An integrin-mediated pathway, initiated by starch grain sedimentation within the amyloplast, may provide the signal amplification necessary to explain the gravitropic response in starch-depleted cultivars.

  16. Loss of β1-integrin from urothelium results in overactive bladder and incontinence in mice: a mechanosensory rather than structural phenotype.

    Kanasaki, Keizo; Yu, Weiqun; von Bodungen, Maximilian; Larigakis, John D; Kanasaki, Megumi; Ayala de la Pena, Francisco; Kalluri, Raghu; Hill, Warren G

    2013-05-01

    Bladder urothelium senses and communicates information about bladder fullness. However, the mechanoreceptors that respond to tissue stretch are poorly defined. Integrins are mechanotransducers in other tissues. Therefore, we eliminated β1-integrin selectively in urothelium of mice using Cre-LoxP targeted gene deletion. β1-Integrin localized to basal/intermediate urothelial cells by confocal microscopy. β1-Integrin conditional-knockout (β1-cKO) mice lacking urothelial β1-integrin exhibited down-regulation and mislocalization of α3- and α5-integrins by immunohistochemistry but, surprisingly, had normal morphology, permeability, and transepithelial resistance when compared with Cre-negative littermate controls. β1-cKO mice were incontinent, as judged by random urine leakage on filter paper (4-fold higher spotting, Pbladder overfilling with 80% longer intercontractile intervals (Phyperactivity (3-fold more prevoid contractions, Pbladder due to abnormal mechanotransduction; more broadly, our findings indicate that urothelium itself directly modulates voiding. PMID:23395910

  17. The cysteine-rich domain of human ADAM 12 supports cell adhesion through syndecans and triggers signaling events that lead to beta1 integrin-dependent cell spreading

    Iba, K; Albrechtsen, R; Gilpin, B;

    2000-01-01

    spread on ADAM 12. However, spreading could be efficiently induced by the addition of either 1 mM Mn(2+) or the beta1 integrin-activating monoclonal antibody 12G10, suggesting that in these carcinoma cells, the ADAM 12-syndecan complex fails to modulate the function of beta1 integrin.......-dependent manner attach to ADAM 12 via members of the syndecan family. After binding to syndecans, mesenchymal cells spread and form focal adhesions and actin stress fibers. Integrin beta1 was responsible for cell spreading because function-blocking monoclonal antibodies completely inhibited cell spreading, and...... chondroblasts lacking beta1 integrin attached but did not spread. These data suggest that mesenchymal cells use syndecans as the initial receptor for the ADAM 12 cysteine-rich domain-mediated cell adhesion, and then the beta1 integrin to induce cell spreading. Interestingly, carcinoma cells attached but did not...

  18. Rhodocytin (aggretin) activates platelets lacking alpha(2)beta(1) integrin, glycoprotein VI, and the ligand-binding domain of glycoprotein Ibalpha

    Bergmeier, W; Bouvard, D; Eble, J A;

    2001-01-01

    collagen may activate platelets by a similar mechanism. In contrast to these findings, we provided evidence that rhodocytin does not bind to alpha(2)beta(1) integrin. Here we show that the Cre/loxP-mediated loss of beta(1) integrin on mouse platelets has no effect on rhodocytin-induced platelet activation......Although alpha(2)beta(1) integrin (glycoprotein Ia/IIa) has been established as a platelet collagen receptor, its role in collagen-induced platelet activation has been controversial. Recently, it has been demonstrated that rhodocytin (also termed aggretin), a snake venom toxin purified from the......, excluding an essential role of alpha(2)beta(1) integrin in this process. Furthermore, proteolytic cleavage of the 45-kDa N-terminal domain of glycoprotein (GP) Ibalpha either on normal or on beta(1)-null platelets had no significant effect on rhodocytin-induced platelet activation. Moreover, mouse platelets...

  19. Identification of inhibitors of α2β1 integrin, members of C-lectin type proteins, in Echis sochureki venom

    Jakubowski, Piotr [Temple University, Department of Biology, Philadelphia, PA 19122 (United States); Calvete, Juan J. [Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Cientificas, 46010 Valencia (Spain); Eble, Johannes A. [Excellence Cluster Cardio-Pulmonary System, Center for Molecular Medicine, Vascular Matrix Biology, Frankfurt University Hospital, Frankfurt am Main 60590 (Germany); Lazarovici, Philip [The Hebrew University of Jerusalem, School of Pharmacy, Institute for Drug Research, Jerusalem 91120 (Israel); Marcinkiewicz, Cezary, E-mail: cmarcink@temple.edu [Temple University, Department of Biology, Philadelphia, PA 19122 (United States)

    2013-05-15

    Snake venom antagonists of α2β1 integrin have been identified as members of a C-lectin type family of proteins (CLP). In the present study, we characterized three new CLPs isolated from Echis sochureki venom, which interact with this integrin. These proteins were purified using a combination of gel filtration, ion exchange chromatography and reverse phase HPLC. Sochicetin-A and sochicetin-B potently inhibited adhesion of cells expressing α2β1 integrin and binding of isolated α2β1 ectodomain to collagen I, as well as bound to recombinant GST-α2A domain in ELISA, whereas activity of sochicetin-C in these assays was approximately two orders of magnitude lower. Structurally, sochicetin-B and sochicetin-C are typical heterodimeric αβ CLPs, whereas sochicetin-A exhibits a trimer of its subunits (αβ){sub 3} in the quaternary structure. Immobilized sochicetins supported adhesion of glioma cell lines, LN18 and LBC3, whereas in a soluble form they partially inhibited adhesion of these cells to collagen I. Glioma cells spread very poorly on sochicetin-A, showing no cytoskeleton rearrangement typical for adhesion to collagen I or fibronectin. Adhesion on CLP does not involve focal adhesion elements, such as vinculin. Sochicetin-A also inhibited collagen-induced platelet aggregation, similar to other CLPs' action on the blood coagulation system. - Highlights: • Isolation of three novel snake venom CLPs inhibiting α2β1 integrin • Reporting hexameric CLP, sochicetin-A with anti-collagen receptor activity • CLPs antagonize the interaction of glioma cells with collagen matrix. • Sochicetin-A does not support glioma cell spreading.

  20. The dermatan sulfate proteoglycan decorin modulates α2β1 integrin and the vimentin intermediate filament system during collagen synthesis.

    Oliver Jungmann

    Full Text Available Decorin, a small leucine-rich proteoglycan harboring a dermatan sulfate chain at its N-terminus, is involved in regulating matrix organization and cell signaling. Loss of the dermatan sulfate of decorin leads to an Ehlers-Danlos syndrome characterized by delayed wound healing. Decorin-null (Dcn(-/- mice display a phenotype similar to that of EDS patients. The fibrillar collagen phenotype of Dcn(-/- mice could be rescued in vitro by decorin but not with decorin lacking the glycosaminoglycan chain. We utilized a 3D cell culture model to investigate the impact of the altered extracellular matrix on Dcn(-/- fibroblasts. Using 2D gel electrophoresis followed by mass spectrometry, we identified vimentin as one of the proteins that was differentially upregulated by the presence of decorin. We discovered that a decorin-deficient matrix leads to abnormal nuclear morphology in the Dcn(-/- fibroblasts. This phenotype could be rescued by the decorin proteoglycan but less efficiently by the decorin protein core. Decorin treatment led to a significant reduction of the α2β1 integrin at day 6 in Dcn(-/- fibroblasts, whereas the protein core had no effect on β1. Interestingly, only the decorin core induced mRNA synthesis, phosphorylation and de novo synthesis of vimentin indicating that the proteoglycan decorin in the extracellular matrix stabilizes the vimentin intermediate filament system. We could support these results in vivo, because the dermis of wild-type mice have more vimentin and less β1 integrin compared to Dcn(-/-. Furthermore, the α2β1 null fibroblasts also showed a reduced amount of vimentin compared to wild-type. These data show for the first time that decorin has an impact on the biology of α2β1 integrin and the vimentin intermediate filament system. Moreover, our findings provide a mechanistic explanation for the reported defects in wound healing associated with the Dcn(-/- phenotype.

  1. Identification of inhibitors of α2β1 integrin, members of C-lectin type proteins, in Echis sochureki venom

    Snake venom antagonists of α2β1 integrin have been identified as members of a C-lectin type family of proteins (CLP). In the present study, we characterized three new CLPs isolated from Echis sochureki venom, which interact with this integrin. These proteins were purified using a combination of gel filtration, ion exchange chromatography and reverse phase HPLC. Sochicetin-A and sochicetin-B potently inhibited adhesion of cells expressing α2β1 integrin and binding of isolated α2β1 ectodomain to collagen I, as well as bound to recombinant GST-α2A domain in ELISA, whereas activity of sochicetin-C in these assays was approximately two orders of magnitude lower. Structurally, sochicetin-B and sochicetin-C are typical heterodimeric αβ CLPs, whereas sochicetin-A exhibits a trimer of its subunits (αβ)3 in the quaternary structure. Immobilized sochicetins supported adhesion of glioma cell lines, LN18 and LBC3, whereas in a soluble form they partially inhibited adhesion of these cells to collagen I. Glioma cells spread very poorly on sochicetin-A, showing no cytoskeleton rearrangement typical for adhesion to collagen I or fibronectin. Adhesion on CLP does not involve focal adhesion elements, such as vinculin. Sochicetin-A also inhibited collagen-induced platelet aggregation, similar to other CLPs' action on the blood coagulation system. - Highlights: • Isolation of three novel snake venom CLPs inhibiting α2β1 integrin • Reporting hexameric CLP, sochicetin-A with anti-collagen receptor activity • CLPs antagonize the interaction of glioma cells with collagen matrix. • Sochicetin-A does not support glioma cell spreading

  2. Laminin isoforms differentially regulate adhesion, spreading, proliferation, and ERK activation of β1 integrin-null cells

    The presence of many laminin receptors of the β1 integrin family on most cells makes it difficult to define the biological functions of other major laminin receptors such as integrin α6β4 and dystroglycan. We therefore tested the binding of a β1 integrin-null cell line GD25 to four different laminin variants. The cells were shown to produce dystroglycan, which based on affinity chromatography bound to laminin-1, -2/4, and -10/11, but not to laminin-5. The cells also expressed the integrin α6Aβ4A variant. GD25 β1 integrin-null cells are known to bind poorly to laminin-1, but we demonstrate here that these cells bind avidly to laminin-2/4, -5, and -10/11. The initial binding at 20 min to each of these laminins could be inhibited by an integrin α6 antibody, but not by a dystroglycan antibody. Hence, integrin α6Aβ4A of GD25 cells was identified as a major receptor for initial GD25 cell adhesion to three out of four tested laminin isoforms. Remarkably, cell adhesion to laminin-5 failed to promote cell spreading, proliferation, and extracellular signal-regulated kinase (ERK) activation, whereas all these responses occurred in response to adhesion to laminin-2/4 or -10/11. The data establish GD25 cells as useful tools to define the role integrin α6Aβ4A and suggest that laminin isoforms have distinctly different capacities to promote cell adhesion and signaling via integrin α6Aβ4A

  3. Insulin-like Growth Factor I Controls Adhesion Strength Mediated by α5β1 Integrins in Motile Carcinoma Cells

    Lynch, Laura; Vodyanik, Pavel I.; Boettiger, David; Guvakova, Marina A

    2005-01-01

    One of the intriguing questions regarding cell motility concerns the mechanism that makes stationary cells move. Here, we provide the first physical evidence that the onset of breast cancer cell motility in response to insulin-like growth factor I (IGF-I) correlates with lowering of adhesion strength from 2.52 ± 0.20 to 1.52 ± 0.13 μdynes/μm2 in cells attached to fibronectin via α5β1 integrin. The adhesion strength depends on the dose of IGF-I and time of IGF-I treatment. Weakening of cell-ma...

  4. Staged stromal extracellular 3D matrices differentially regulate breast cancer cell responses through PI3K and beta1-integrins

    Interactions between cancer cells and stroma are critical for growth and invasiveness of epithelial tumors. The biochemical mechanisms behind tumor-stromal interactions leading to increased invasiveness and metastasis are mostly unknown. The goal of this study was to analyze the direct effects of staged stroma-derived extracellular matrices on breast cancer cell behavior. Early and late three-dimensional matrices were produced by NIH-3T3 and tumor-associated murine fibroblasts, respectively. After removing fibroblasts, extracted matrices were re-cultured with breast epithelial cells of assorted characteristics: MCF-10A (non-tumorigenic), MCF-7 (tumorigenic, non-invasive), and MDA-MB-231 (tumorigenic, invasive). Effects prompted by staged matrices on epithelial cell's growth, morphology and invasion were determined. Also, matrix-induced velocity, directionality and relative track orientation of invasive cells were assessed in the presence or absence of inhibitors of phosphoinositide-3 kinase (PI3K) and/or beta-1 integrin. We observed that assorted breast epithelial cells reacted differently to two-dimensional vs. staged, control (early) and tumor-associated (late), three-dimensional matrices. MCF-10A had a proliferative advantage on two-dimensional substrates while MCF-7 and MDA-MB-231 showed no difference. MCF-10A and MCF-7 formed morphologically distinguishable aggregates within three-dimensional matrices, while MDA-MB-231 exhibited increased spindle-shape morphologies and directional movements within three-dimensional matrices. Furthermore, MDA-MB-231 acquired a pattern of parallel oriented organization within tumor-associated, but not control matrices. Moreover, tumor-associated matrices induced PI3K and beta1-integrin dependent Akt/PKB activity in MDA-MB-231 cells. Interestingly, beta1-integrin (but not PI3K) regulated tumor-associated matrix-induced mesenchymal invasion which, when inhibited, resulted in a change of invasive strategy rather than impeding

  5. Ofloxacin induces apoptosis via β1 integrin-EGFR-Rac1-Nox2 pathway in microencapsulated chondrocytes

    Sheng, Zhi-Guo [State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Science, Chinese Academy of Sciences, 18 Shuangqing Road, Beijing 100085 (China); Huang, Wei [Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 1000191 (China); Liu, Yu-Xiang [State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Science, Chinese Academy of Sciences, 18 Shuangqing Road, Beijing 100085 (China); Yuan, Ye [Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing 100850 (China); Zhu, Ben-Zhan, E-mail: bzhu@rcees.ac.cn [State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Science, Chinese Academy of Sciences, 18 Shuangqing Road, Beijing 100085 (China); Linus Pauling Institute, Oregon State University, Corvallis, OR 97331 (United States)

    2013-02-15

    Quinolones (QNs)-induced arthropathy is an important toxic side-effect in immature animals leading to the restriction of their therapeutic use in pediatrics. Ofloxacin, a typical QN, was found to induce the chondrocytes apoptosis in the early phase (12–48 h) of arthropathy in our previous study. However, the exact mechanism(s) is unclear. Microencapsulated juvenile rabbit joint chondrocytes, a three-dimensional culture system, is utilized to perform the present study. Ofloxacin, at a therapeutically relevant concentration (10 μg/ml), disturbs the interaction between β1 integrin and activated intracellular signaling proteins at 12 h, which is inhibited when supplementing Mg{sup 2+}. Intracellular reactive oxygen species (ROS) significantly increases in a time-dependent manner after exposure to ofloxacin for 12–48 h. Furthermore, ofloxacin markedly enhances the level of activated Rac1 and epidermal growth factor receptor (EGFR) phosphorylation, and its inhibition in turn reduces the ROS production, apoptosis and Rac1 activation. Silencing Nox2, Rac1 or supplementing Mg{sup 2+} inhibits ROS accumulation, apoptosis occurrence and EGFR phosphorylation induced by ofloxacin. However, depletion of Nox2, Rac1 and inhibition of EGFR do not affect ofloxacin-mediated loss of interaction between β1 integrin and activated intracellular signaling proteins. In addition, ofloxacin also induces Vav2 phosphorylation, which is markedly suppressed after inactivating EGFR or supplementing Mg{sup 2+}. These results suggest that ofloxacin causes Nox2-mediated intracellular ROS production by disrupting the β1 integrin function and then activating the EGFR-Vav2-Rac1 pathway, finally resulting in apoptosis within 12–48 h exposure. The present study provides a novel insight regarding the potential role of Nox-driven ROS in QNs-induced arthropathy. - Highlights: ► Ofloxacin induces Nox2-driven ROS in encapsulated chondrocyte at 12–48 h. ► Ofloxacin stimulates ROS production via

  6. Airway Hyperresponsiveness in Asthma Model Occurs Independently of Secretion of β1 Integrins in Airway Wall and Focal Adhesions Proteins Down Regulation.

    Álvarez-Santos, Mayra; Carbajal, Verónica; Tellez-Jiménez, Olivia; Martínez-Cordero, Erasmo; Ruiz, Victor; Hernández-Pando, Rogelio; Lascurain, Ricardo; Santibañez-Salgado, Alfredo; Bazan-Perkins, Blanca

    2016-10-01

    The extracellular domains of some membrane proteins can be shed from the cell. A similar phenomenon occurs with β1 integrins (α1β1 and α2β1) in guinea pig. The putative role of β1 integrin subunit alterations due to shedding in airway smooth muscle (ASM) in an allergic asthma model was evaluated. Guinea pigs were sensitized and challenged with antigen. Antigenic challenges induced bronchoobstruction and hyperresponsiveness at the third antigenic challenge. Immunohistochemistry and immunoelectronmicroscopy studies showed that the cytosolic and extracellular domains of the β1 integrin subunit shared the same distribution in airway structures in both groups. Various polypeptides with similar molecular weights were detected with both the cytosolic and extracellular β1 integrin subunit antibodies in isolated airway myocytes and the connective tissue that surrounds the ASM bundle. Flow cytometry and Western blot studies showed that the expression of cytosolic and extracellular β1 integrin subunit domains in ASM was similar between groups. An increment of ITGB1 mRNA in ASM was observed in the asthma model group. RACE-PCR of ITGB1 in ASM did not show splicing variants. The expression levels of integrin-linked kinase (ILK) and paxillin diminished in the asthma model, but not talin. The levels of phosphorylation of myosin phosphatase target subunit 1 (MYPT1) at Thr(696) increased in asthma model. Our work suggests that β1 integrin is secreted in guinea pig airway wall. This secretion is not altered in asthma model; nevertheless, β1 integrin cytodomain assembly proteins in focal cell adhesions in which ILK and paxillin are involved are altered in asthma model. J. Cell. Biochem. 117: 2385-2396, 2016. © 2016 Wiley Periodicals, Inc. PMID:26969873

  7. The NLRP3 Inflammasome Is a Pathogen Sensor for Invasive Entamoeba histolytica via Activation of α5β1 Integrin at the Macrophage-Amebae Intercellular Junction.

    Leanne Mortimer

    2015-05-01

    Full Text Available Entamoeba histolytica (Eh is an extracellular protozoan parasite of humans that invades the colon to cause life-threatening intestinal and extra-intestinal amebiasis. Colonized Eh is asymptomatic, however, when trophozoites adhere to host cells there is a considerable inflammatory response that is critical in the pathogenesis of amebiasis. The host and/or parasite factors that trigger the inflammatory response to invading Eh are not well understood. We recently identified that Eh adherence to macrophages induces inflammasome activation and in the present study we sought to determine the molecular events upon contact that coordinates this response. Here we report that Eh contact-dependent activation of α5β1 integrin is critical for activation of the NLRP3 inflammasome. Eh-macrophage contact triggered recruitment of α5β1 integrin and NLRP3 into the intercellular junction, where α5β1 integrin underwent activation by an integrin-binding cysteine protease on the parasite surface, termed EhCP5. As a result of its activation, α5β1 integrin induced ATP release into the extracellular space through opening of pannexin-1 channels that signalled through P2X7 receptors to deliver a critical co-stimulatory signal that activated the NLRP3 inflammasome. Both the cysteine protease activity and integrin-binding domain of EhCP5 were required to trigger α5β1 integrin that led to ATP release and NLRP3 inflammasome activation. These findings reveal engagement of α5β1 integrin across the parasite-host junction is a key regulatory step that initiates robust inflammatory responses to Eh. We propose that α5β1 integrin distinguishes Eh direct contact and functions with NLRP3 as pathogenicity sensor for invasive Eh infection.

  8. α2β1 integrin affects metastatic potential of ovarian carcinoma spheroids by supporting disaggregation and proteolysis

    Ackland Margaret

    2007-01-01

    Full Text Available Abstract Background Ovarian cancer is characterized by a wide-spread intra-abdominal metastases which represents a major clinical hurdle in the prognosis and management of the disease. A significant proportion of ovarian cancer cells in peritoneal ascites exist as multicellular aggregates or spheroids. We hypothesize that these cellular aggregates or spheroids are invasive with the capacity to survive and implant on the peritoneal surface. This study was designed to elucidate early inherent mechanism(s of spheroid survival, growth and disaggregation required for peritoneal metastases Methods In this study, we determined the growth pattern and adhesive capacity of ovarian cancer cell lines (HEY and OVHS1 grown as spheroids, using the well established liquid overlay technique, and compared them to a normal ovarian cell line (IOSE29 and cancer cells grown as a monolayer. The proteolytic capacity of these spheroids was compared with cells grown as a monolayer using a gelatin zymography assay to analyze secreted MMP-2/9 in conditioned serum-free medium. The disaggregation of cancer cell line spheroids was determined on extracellular matrices (ECM such as laminin (LM, fibronectin (FN and collagen (CI and the expression of α2, α3, αv, α6 and β1 interin was determined by flow cytometric analysis. Neutralizing antibodies against α2, β1 subunits and α2β1 integrin was used to inhibit disaggregation as well as activation of MMPs in spheroids. Results We demonstrate that ovarian cancer cell lines grown as spheroids can sustain growth for 10 days while the normal ovarian cell line failed to grow beyond 2 days. Compared to cells grown as a monolayer, cancer cells grown as spheroids demonstrated no change in adhesion for up to 4 days, while IOSE29 cells had a 2–4-fold loss of adhesion within 2 days. Cancer cell spheroids disaggregated on extracellular matrices (ECM and demonstrated enhanced expression of secreted pro-MMP2 as well as activated MMP2

  9. THE α4β1 INTEGRIN AND THE EDA DOMAIN OF FIBRONECTIN REGULATE A PROFIBROTIC PHENOTYPE IN DERMAL FIBROBLASTS*

    Shinde, Arti V.; Kelsh, Rhiannon; Peters, John H.; Sekiguchi, Kiyotoshi; Van De Water, Livingston; McKeown-Longo, Paula J.

    2015-01-01

    Prompt deposition of fibronectin-rich extracellular matrix is a critical feature of normal development and the host-response to injury. Fibronectin isoforms that include the EDA and EDB domains are prominent in these fibronectin matrices. We now report using human dermal fibroblast cultures that the EDA domain of fibronectin or EDA-derived peptides modeled after the C-C’ loop promote stress fiber formation and myosin-light chain phosphorylation. These changes are accompanied by an increase in fibronectin synthesis and fibrillogenesis. These effects are blocked by pretreating cells with either siRNA or blocking antibody to the α4 integrin. Our data indicate that the interaction between the α4β1 integrin and the EDA domain of fibronectin helps to drive tissue fibrosis by promoting a contractile phenotype and an increase in fibronectin synthesis and deposition. PMID:25433338

  10. The α4β1 integrin and the EDA domain of fibronectin regulate a profibrotic phenotype in dermal fibroblasts.

    Shinde, Arti V; Kelsh, Rhiannon; Peters, John H; Sekiguchi, Kiyotoshi; Van De Water, Livingston; McKeown-Longo, Paula J

    2015-01-01

    Prompt deposition of fibronectin-rich extracellular matrix is a critical feature of normal development and the host-response to injury. Fibronectin isoforms that include the EDA and EDB domains are prominent in these fibronectin matrices. We now report using human dermal fibroblast cultures that the EDA domain of fibronectin or EDA-derived peptides modeled after the C-C' loop promote stress fiber formation and myosin-light chain phosphorylation. These changes are accompanied by an increase in fibronectin synthesis and fibrillogenesis. These effects are blocked by pretreating cells with either siRNA or blocking antibody to the α4 integrin. Our data indicate that the interaction between the α4β1 integrin and the EDA domain of fibronectin helps to drive tissue fibrosis by promoting a contractile phenotype and an increase in fibronectin synthesis and deposition. PMID:25433338

  11. The Activation of β1-integrin by Type I Collagen Coupling with the Hedgehog Pathway Promotes the Epithelial-Mesenchymal Transition in Pancreatic Cancer.

    Duan, Wanxing; Ma, Jiguang; Ma, Qingyong; Xu, Qinhong; Lei, Jianjun; Han, Liang; Li, Xuqi; Wang, Zheng; Wu, Zheng; Lv, Shifang; Ma, Zhenhua; Liu, Mouzhu; Wang, Fengfei; Wu, Erxi

    2014-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is characterized by the excessive deposition of extracellular matrix (ECM), which is thought to contribute to this tumor's malignant behavior. However, the detailed mechanism and the contribution of excessive deposition of ECM in PDAC progression remain unclear. A better understanding of the mechanism involved in this process is essential for the design of new effective therapies. In this study, we demonstrated that pancreatic cancer cells exhibited increased proliferation and decreased apoptosis in response to type I collagen. In addition, PDAC cells exposed to type I collagen lost the expression of E-cadherin and increased expression of mesenchymal markers, including N-cadherin and vimentin. This epithelial- mesenchymal transition (EMT) was correlated with enhanced cell migration and invasiveness. Knockdown of β1-integrin abolished the effects induced by type I collagen, and further investigation revealed that type I collagen activates β1-integrin (marked by phosphorylation of β1 integrin downstream effectors, focal adhesion kinase [FAK], AKT, and ERK) accompanied by markedly up-regulation of Gli-1, a component of the Hedgehog (HH) pathway. Knockdown of Gli-1 reversed the effects of type I collagen on PDAC invasion and EMT. These results suggest that there is cross-talk between the β1-integrin signaling pathway and the HH pathway in pancreatic cancer and that activation of the HH pathway plays a key role in the type I collagen-induced effects on pancreatic cancer. PMID:24720337

  12. Endotoxin/lipopolysaccharide activates NF-kappa B and enhances tumor cell adhesion and invasion through a beta 1 integrin-dependent mechanism.

    Wang, Jiang Huai

    2012-02-03

    Beta(1) integrins play a crucial role in supporting tumor cell attachment to and invasion into the extracellular matrix. Endotoxin\\/LPS introduced by surgery has been shown to enhance tumor metastasis in a murine model. Here we show the direct effect of LPS on tumor cell adhesion and invasion in extracellular matrix proteins through a beta(1) integrin-dependent pathway. The human colorectal tumor cell lines SW480 and SW620 constitutively expressed high levels of the beta(1) subunit, whereas various low levels of alpha(1), alpha(2), alpha(4), and alpha(6) expression were detected. SW480 and SW620 did not express membrane-bound CD14; however, LPS in the presence of soluble CD14 (sCD14) significantly up-regulated beta(1) integrin expression; enhanced tumor cell attachment to fibronectin, collagen I, and laminin; and strongly promoted tumor cell invasion through the Matrigel. Anti-beta(1) blocking mAbs (4B4 and 6S6) abrogated LPS- plus sCD14-induced tumor cell adhesion and invasion. Furthermore, LPS, when combined with sCD14, resulted in NF-kappaB activation in both SW480 and SW620 cells. Inhibition of the NF-kappaB pathway significantly attenuated LPS-induced up-regulation of beta(1) integrin expression and prevented tumor cell adhesion and invasion. These results provide direct evidence that although SW480 and SW620 cells do not express membrane-bound CD14, LPS in the presence of sCD14 can activate NF-kappaB, up-regulate beta(1) integrin expression, and subsequently promote tumor cell adhesion and invasion. Moreover, LPS-induced tumor cell attachment to and invasion through extracellular matrix proteins is beta(1) subunit-dependent.

  13. Unique DNA repair properties of a xeroderma pigmentosum revertant.

    Cleaver, J.E.; Cortés, F; Lutze, L H; Morgan, W F; Player, A N; D. L. Mitchell

    1987-01-01

    A group A xeroderma pigmentosum revertant with normal sensitivity was created by chemical mutagenesis. It repaired (6-4) photoproducts normally but not pyrimidine dimers and had near normal levels of repair replication, sister chromatid exchange, and mutagenesis from UV light. The rate of UV-induced mutation in a shuttle vector, however, was as high as the rate in the parental xeroderma pigmentosum cell line.

  14. The Interaction of CD154 with the α5β1 Integrin Inhibits Fas-Induced T Cell Death.

    Bachsais, Meriem; Naddaf, Nadim; Yacoub, Daniel; Salti, Suzanne; Alaaeddine, Nada; Aoudjit, Fawzi; Hassan, Ghada S; Mourad, Walid

    2016-01-01

    CD154, a critical regulator of the immune response, is usually associated with chronic inflammatory, autoimmune diseases as well as malignant disorders. In addition to its classical receptor CD40, CD154 is capable of binding other receptors, members of the integrin family, the αIIbβ3, αMβ2 and α5β1. Given the role attributed to integrins and particularly the β1 integrins in inhibiting apoptotic events in normal as well as malignant T cells, we were highly interested in investigating the role of the CD154/α5β1 interaction in promoting survival of malignant T cells contributing as such to tumor development and/or propagation. To support our hypothesis, we first show that soluble CD154 binds to the T-cell acute lymphoblastic leukemia cell line, Jurkat E6.1 in a α5β1-dependent manner. Binding of soluble CD154 to α5β1 integrin of Jurkat cells leads to the activation of key survival proteins, including the p38 and ERK1/2 mitogen-activated protein kinases (MAPKs), phosphoinositide 3 kinase (PI-3K), and Akt. Interestingly, soluble CD154 significantly inhibits Fas-mediated apoptosis in T cell leukemia-lymphoma cell lines, Jurkat E6.1 and HUT78 cells, an important hallmark of T cell survival during malignancy progression. These anti-apoptotic effects were mainly mediated by the activation of the PI-3K/Akt pathway but also involved the p38 and the ERK1/2 MAPKs cascades. Our data also demonstrated that the CD154-triggered inhibition of the Fas-mediated cell death response was dependent on a suppression of caspase-8 cleavage, but independent of de novo protein synthesis or alterations in Fas expression on cell surface. Together, our results highlight the impact of the CD154/α5β1 interaction in T cell function/survival and identify novel targets for the treatment of malignant disorders, particularly of T cell origin. PMID:27391025

  15. α5β1 integrin recycling promotes Arp2/3-independent cancer cell invasion via the formin FHOD3

    Paul, Nikki R.; Allen, Jennifer L.; Chapman, Anna; Morlan-Mairal, Maria; Zindy, Egor; Jacquemet, Guillaume; Fernandez del Ama, Laura; Ferizovic, Nermina; Green, David M.; Howe, Jonathan D.; Ehler, Elisabeth; Hurlstone, Adam

    2015-01-01

    Invasive migration in 3D extracellular matrix (ECM) is crucial to cancer metastasis, yet little is known of the molecular mechanisms that drive reorganization of the cytoskeleton as cancer cells disseminate in vivo. 2D Rac-driven lamellipodial migration is well understood, but how these features apply to 3D migration is not clear. We find that lamellipodia-like protrusions and retrograde actin flow are indeed observed in cells moving in 3D ECM. However, Rab-coupling protein (RCP)-driven endocytic recycling of α5β1 integrin enhances invasive migration of cancer cells into fibronectin-rich 3D ECM, driven by RhoA and filopodial spike-based protrusions, not lamellipodia. Furthermore, we show that actin spike protrusions are Arp2/3-independent. Dynamic actin spike assembly in cells invading in vitro and in vivo is regulated by Formin homology-2 domain containing 3 (FHOD3), which is activated by RhoA/ROCK, establishing a novel mechanism through which the RCP–α5β1 pathway reprograms the actin cytoskeleton to promote invasive migration and local invasion in vivo. PMID:26370503

  16. Production of IL1-beta by ovarian cancer cells induces mesothelial cell beta1-integrin expression facilitating peritoneal dissemination

    Watanabe Takafumi

    2012-02-01

    Full Text Available Abstract Background A crucial step in the metastatic spread of ovarian cancer (OC is the adhesion and implantation of tumor cells to the peritoneal mesothelium. In order to study this step in the cascade, we derived a pro-metastatic human ovarian carcinoma cell line (MFOC3 from the non-metastatic FOC3 line. Methods Molecular profiling of the isogeneic lines identified differentially expressed genes, and investigation for a role in dissemination for specific factors was achieved by development of a co-culture adhesion assay utilizing monolayers of human mesothelial cells. Results After murine intraperitoneal inoculation, the FOC3 cell line formed no metastases, but the MFOC3 subline formed metastases in > 80% of SCID mice. MFOC3 cells also adhered 2-3 times more avidly to mesothelial monolayers. This adhesion was inhibited by neutralizing antibodies to IL-1β and enhanced by recombinant IL-1β (p in vitro and significantly reduced metastases in vivo. Immunohistochemical analysis of a cohort of 96 ovarian cancer cases showed that negative IL-1β expression was significantly associated with an improved overall survival rate. Conclusions These results suggest that a IL-1β/β1-integrin axis plays a role in ovarian tumor cell adhesion to mesothelia, a crucial step in ovarian cancer dissemination.

  17. SNARE-mediated trafficking of α5β1 integrin is required for spreading in CHO cells

    In this study, the role of SNARE-mediated membrane traffic in regulating integrin localization was examined and the requirement for SNARE function in cellular spreading was quantitatively assessed. Membrane traffic was inhibited with the VAMP-specific catalytic light chain from tetanus toxin (TeTx-LC), a dominant-negative form (E329Q) of N-ethylmaleimide-sensitive fusion protein (NSF), and brefeldin A (BfA). Inhibition of membrane traffic with either E329Q-NSF or TeTx-LC, but not BfA, significantly inhibited spreading of CHO cells on fibronectin. Spreading was rescued in TeTx-LC-expressing cells by co-transfection with a TeTx-resistant cellubrevin/VAMP3. E329Q-NSF, a general inhibitor of SNARE function, was a more potent inhibitor of cell spreading than TeTx-LC, suggesting that tetanus toxin-insensitive SNAREs contribute to adhesion. It was found that E329Q-NSF prevented trafficking of α5β1 integrins from a central Rab11-containing compartment to sites of protrusion during cell adhesion, while TeTx-LC delayed this trafficking. These results are consistent with a model of cellular adhesion that implicates SNARE function as an important component of integrin trafficking during the process of cell spreading

  18. Endorepellin, the C-terminal angiostatic module of perlecan, enhances collagen-platelet responses via the α2β1-integrin receptor

    Bix, Gregory; Iozzo, Rex A.; Woodall, Ben; Burrows, Michelle; McQuillan, Angela; Campbell, Shelly; Fields, Gregg B.; Iozzo, Renato V.

    2007-01-01

    Endorepellin, a C-terminal fragment of the vascular basement membrane proteoglycan perlecan, inhibits angiogenesis via the α2β1-integrin receptor. Because this integrin is also implicated in platelet-collagen responses and because endorepellin or its fragments are generated in response to injury and inflammation, we hypothesized that endorepellin could also affect platelet biology. We discovered that endorepellin supported α2β1-dependent platelet adhesion, without appreciably activating or ag...

  19. Treatment of marrow stroma with interferon-alpha restores normal beta 1 integrin-dependent adhesion of chronic myelogenous leukemia hematopoietic progenitors. Role of MIP-1 alpha.

    R Bhatia; McGlave, P B; Verfaillie, C M

    1995-01-01

    The mechanisms by which interferon-alpha (IFN-alpha) restores normal hematopoiesis in chronic myelogenous leukemia (CML) are not well understood. We have recently demonstrated that IFN-alpha acts directly on CML hematopoietic progenitors to restore their adhesion to marrow stroma by modulating beta 1 integrin receptor function. In the present study we examined the effect of IFN-alpha treatment of marrow stroma on subsequent adhesion of CML progenitors. Stromal layers were preincubated with IF...

  20. Tauroursodeoxycholate Protects Rat Hepatocytes from Bile Acid-Induced Apoptosis via β1-Integrin- and Protein Kinase A-Dependent Mechanisms

    Annika Sommerfeld

    2015-05-01

    Full Text Available Background/Aims: Ursodeoxycholic acid, which in vivo is rapidly converted into its taurine conjugate, is frequently used for the treatment of cholestatic liver disease. Apart from its choleretic effects, tauroursodeoxycholate (TUDC can protect hepatocytes from bile acid-induced apoptosis, but the mechanisms underlying its anti-apoptotic effects are poorly understood. Methods: These mechanisms were investigated in perfused rat liver and isolated rat hepatocytes. Results: It was found that TUDC inhibited the glycochenodeoxycholate (GCDC-induced activation of the CD95 death receptor at the level of association between CD95 and the epidermal growth factor receptor. This was due to a rapid TUDC-induced β1-integrin-dependent cyclic AMP (cAMP signal with induction of the dual specificity mitogen-activated protein (MAP kinase phosphatase 1 (MKP-1, which prevented GCDC-induced phosphorylation of mitogen-activated protein kinase kinase 4 (MKK4 and c-jun-NH2-terminal kinase (JNK activation. Furthermore, TUDC induced a protein kinase A (PKA-mediated serine/threonine phosphorylation of the CD95, which was recently identified as an internalization signal for CD95. Furthermore, TUDC inhibited GCDC-induced CD95 targeting to the plasma membrane in a β1-integrin-and PKA-dependent manner. In line with this, the β1-integrin siRNA knockdown in sodium taurocholate cotransporting polypeptide (Ntcp-transfected HepG2 cells abolished the protective effect of TUDC against GCDC-induced apoptosis. Conclusion: TUDC exerts its anti-apoptotic effect via a β1-integrin-mediated formation of cAMP, which prevents CD95 activation by hydrophobic bile acids at the levels of JNK activation and CD95 serine/threonine phosphorylation.

  1. Cellular partitioning of beta-1 integrins and their phosphorylated forms is altered after transformation by Rous sarcoma virus or treatment with cytochalasin D.

    Haimovich, B; Aneskievich, B J; Boettiger, D

    1991-01-01

    A sequential extraction procedure of 3-[(3-cholamidopropyl)-dimethylammonio]-1-propane sulfonate (CHAPS) buffer followed by RIPA or Laemmli sample buffer was developed to define two distinct subpopulations of beta-1 integrins in primary chicken embryo fibroblasts. Extraction of cells in culture revealed an association of adhesion plaque-localized integrin with the CHAPS-insoluble fraction. Phosphorylated integrins were found in both fractions, but the specific phosphorylation was 12-fold high...

  2. Plumieribetin, a Fish Lectin Homologous to Mannose-binding B-type Lectins, Inhibits the Collagen-binding α1β1 Integrin*

    de Santana Evangelista, Karla; Andrich, Filipe; Figueiredo de Rezende, Flávia; Niland, Stephan; Cordeiro, Marta N.; Horlacher, Tim; Castelli, Riccardo; Schmidt-Hederich, Alletta; Peter H. Seeberger; Sanchez, Eladio F.; Richardson, Michael; Gomes de Figueiredo, Suely; Eble, Johannes A.

    2009-01-01

    Recently, a few fish proteins have been described with a high homology to B-type lectins of monocotyledonous plants. Because of their mannose binding activity, they have been ascribed a role in innate immunity. By screening various fish venoms for their integrin inhibitory activity, we isolated a homologous protein from the fin stings and skin mucus of the scorpionfish (Scorpaena plumieri). This protein inhibits α1β1 integrin binding to basement membrane collagen IV. By protein chemical and s...

  3. Differential β3 and β1 Integrin Expression in Bone Marrow and Cortical Bone of Estrogen Deficient Rats.

    Voisin, Muriel; McNamara, Laoise M

    2015-09-01

    Integrin-based (β3 ) attachments to the extracellular matrix (ECM) on osteocyte cell processes have recently been proposed to play an important role in facilitating osteocyte mechanosensation. However, it is not yet known whether integrin expression is altered in the mechanoregulatory osteocytes during osteoporosis. The objective of this study was to test the hypothesis that the expression of integrin-based mechanosensory complexes (β1 and β3 integrins) is altered as a direct response to estrogen deficiency, in an estrogen deficient animal model of osteoporosis. Four weeks post-operatively, immunohistochemistry was used to detect for β1 and β3 integrin subunits in bone tissue and marrow of ovariectomized (OVX; N = 4) and SHAM (N = 4) operated animals. A tartrate resistant acid phosphatase (TRAP) control stain was performed to quantify the presence of osteoclasts in the bone marrow and bone surfaces. Image analysis was performed to quantify expression patterns in different biological compartments, that is, bone marrow, endosteum, and cortical bone. Our results showed that β1 integrins were ubiquitously expressed throughout the bone and marrow, for both OVX and SHAM groups. β3 integrin subunit expression was lower in bone cells from osteoporotic animals compared to controls, whereas β3 expression in marrow cells did not differ significantly between groups. At the endosteum no difference was observed in β3 integrin subunit expression. As expected, the number of osteoclasts was higher in the OVX group validating an imbalance in bone remodeling. We propose that a reduction in β3 integrin expression in osteocytes might impair mechanosensation by bone cells during estrogen deficiency. PMID:25974241

  4. Bone marrow-derived mesenchymal stem cells enhance angiogenesis via their α6β1 integrin receptor

    Bone marrow-derived mesenchymal stem cells (BMSCs) facilitate the angiogenic response of endothelial cells (ECs) within three-dimensional (3D) matrices in vivo and in engineered tissues in vitro in part through paracrine mediators and by acting as stabilizing pericytes. However, the molecular interactions between BMSCs and nascent tubules during the process of angiogenesis are not fully understood. In this study, we have used a tractable 3D co-culture model to explore the functional role of the α6β1 integrin adhesion receptor on BMSCs in sprouting angiogenesis. We report that knockdown of the α6 integrin subunit in BMSCs significantly reduces capillary sprouting, and causes their failure to associate with the nascent vessels. Furthermore, we demonstrate that the BMSCs with attenuated α6 integrin proliferate at a significantly lower rate relative to either control cells expressing non-targeting shRNA or wild type BMSCs; however, despite adding more cells to compensate for this deficit in proliferation, deficient sprouting persists. Collectively, our findings demonstrate that the α6 integrin subunit in BMSCs is important for their ability to stimulate vessel morphogenesis. This conclusion may have important implications in the optimization of cell-based strategies to promote angiogenesis. Highlights: • BMSCs stimulate angiogenesis, but the mechanisms remain unclear. • We silenced the expression of the α6 integrin subunit in BMSCs. • Silencing this receptor subunit significantly inhibited angiogenic sprouting. • Knocking down α6 integrin affected laminin and αSMA expression. • Silencing α6 integrin expression also reduced BMSC proliferation

  5. Bone marrow-derived mesenchymal stem cells enhance angiogenesis via their α6β1 integrin receptor

    Carrion, Bita; Kong, Yen P. [Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109 (United States); Kaigler, Darnell [Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109 (United States); Department of Periodontics and Oral Medicine, University of Michigan, Ann Arbor, MI 48109 (United States); Putnam, Andrew J., E-mail: putnam@umich.edu [Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109 (United States)

    2013-11-15

    Bone marrow-derived mesenchymal stem cells (BMSCs) facilitate the angiogenic response of endothelial cells (ECs) within three-dimensional (3D) matrices in vivo and in engineered tissues in vitro in part through paracrine mediators and by acting as stabilizing pericytes. However, the molecular interactions between BMSCs and nascent tubules during the process of angiogenesis are not fully understood. In this study, we have used a tractable 3D co-culture model to explore the functional role of the α6β1 integrin adhesion receptor on BMSCs in sprouting angiogenesis. We report that knockdown of the α6 integrin subunit in BMSCs significantly reduces capillary sprouting, and causes their failure to associate with the nascent vessels. Furthermore, we demonstrate that the BMSCs with attenuated α6 integrin proliferate at a significantly lower rate relative to either control cells expressing non-targeting shRNA or wild type BMSCs; however, despite adding more cells to compensate for this deficit in proliferation, deficient sprouting persists. Collectively, our findings demonstrate that the α6 integrin subunit in BMSCs is important for their ability to stimulate vessel morphogenesis. This conclusion may have important implications in the optimization of cell-based strategies to promote angiogenesis. Highlights: • BMSCs stimulate angiogenesis, but the mechanisms remain unclear. • We silenced the expression of the α6 integrin subunit in BMSCs. • Silencing this receptor subunit significantly inhibited angiogenic sprouting. • Knocking down α6 integrin affected laminin and αSMA expression. • Silencing α6 integrin expression also reduced BMSC proliferation.

  6. Metastatic dissemination of human ovarian epithelial carcinoma is promoted by alpha2beta1-integrin-mediated interaction with type I collagen.

    Fishman, D A; Kearns, A; Chilukuri, K; Bafetti, L M; O'Toole, E A; Georgacopoulos, J; Ravosa, M J; Stack, M S

    1998-01-01

    Metastatic dissemination of epithelial ovarian carcinoma is thought to be mediated via tumor cell exfoliation into the peritoneal cavity, followed by adhesion to and invasion through the mesothelium which overlies the contents of the peritoneal cavity. In this study, we have utilized short-term primary cultures to analyze the effect of specific extracellular matrix proteins on properties of human ovarian epithelial carcinoma cells which contribute to the invasive phenotype. Analysis of cell:matrix adhesive profiles indicated that ovarian carcinoma cells adhere preferentially to type I collagen. Immunoprecipitation analyses demonstrated the presence of the collagen-binding alpha2beta1 integrin in biotin-labeled ovarian carcinoma cell membranes, and cellular adhesion was inhibited by blocking antibodies directed against the alpha2 and beta1 integrin subunits. The alpha2beta1-binding peptide Asp-Gly-Glu-Ala (DGEA) was also moderately effective at blocking adhesion to collagen relative to the control peptide Ala-Gly-Glu-Ala (AGEA). Analysis of cell motility on protein-coated colloidal gold coverslips demonstrated that ovarian carcinoma cells migrate preferentially on type I collagen coated surfaces. Type I collagen promoted migration in a concentration-dependent, saturable manner, with maximal migration observed at a collagen-coating concentration of 50 microg/ml. Migration on collagen was inhibited by antibodies directed against the alpha2 and beta1 integrin subunits and by DGEA peptide, providing evidence for the role of the alpha2beta1 integrin in ovarian carcinoma cell motility. Culturing ovarian carcinoma cells on type I collagen gels led to a significant increase in conversion of the matrix metalloproteinase 2 zymogen to the 66-kD form, suggesting that adhesion to collagen also influences matrix-degrading proteinases. These data suggest that alpha2beta1-integrin-mediated interaction of ovarian carcinoma cells with type I collagen, a protein prevalent both in the

  7. A vortex venturi for reverting antimisting fuel properties

    Szetela, E. J.; Tevelde, J.

    1983-01-01

    The level of degradation of antimisting fuel polymers such as FM-9 which must be accomplished in order to use antimisting fuel in existing engines may require the use of cavitation. The hydrodynamic shear produced by the collapse of vapor bubbles is capable of producing more splitting of polymeric molecules than mechanically-induced shear. A program has been carried out to investigate the possibility of using a cavitating venturi with rotating flow as a fuel reverter. This investigation included the effects of a swirl-inducing twisted tape upstream of the throat, inlet pressure, recovery pressure ratio and a pintle for varying throat area. A correlation of the data was produced, system concepts for using the vortex venturi were investigated and problem areas were delineated.

  8. Cellular growth and survival are mediated by beta 1 integrins in normal human breast epithelium but not in breast carcinoma

    Howlett, Anthony R; Bailey, Nina; Damsky, Caroline; Petersen, Ole W; Bissell, Mina J

    1994-11-28

    capacity to form colonies. Thus under our culture conditions breast acinar formation is at least a two-step process involving {beta}1-integrin-dependent cellular growth followed by polarization of the cells into organized structures. The regulation of this pathway appears to be impaired or lost in the tumor cells, suggesting that tumor colony formation occurs by independent mechanisms and that loss of proper integrinmediated cell-ECM interaction may be critical to breast tumor formation.

  9. Essential function for PDLIM2 in cell polarization in three-dimensional cultures by feedback regulation of the β1-integrin-RhoA signaling axis.

    Deevi, Ravi Kiran; Cox, Orla T; O'Connor, Rosemary

    2014-05-01

    PDLIM2 is a cytoskeletal and nuclear PDZ-LIM domain protein that regulates the stability of Nuclear Factor kappa-B (NFκB) and other transcription factors, and is required for polarized cell migration. PDLIM2 expression is suppressed by methylation in different cancers, but is strongly expressed in invasive breast cancer cells that have undergone an Epithelial Mesenchymal Transition (EMT). PDLIM2 is also expressed in non-transformed breast myoepithelial MCF10A cells and here we asked whether it is important for maintaining the polarized, epithelial phenotype of these cells. Suppression of PDLIM2 in MCF10A cells was sufficient to disrupt cell polarization and acini formation with increased proliferation and reduced apoptosis in the luminal space compared to control acini with hollow lumina. Spheroids with suppressed PDLIM2 exhibited increased expression of cell-cell and cell-matrix adhesion proteins including beta 1 (β1) integrin. Interestingly, levels of the Insulin-like growth factor 1 receptor (IGF-1 R) and Receptor of activated protein kinase C 1 (RACK1), which scaffolds IGF-1R to β1 integrin, were also increased, indicating a transformed phenotype. Focal Adhesion Kinase (FAK) and cofilin phosphorylation, and RhoA Guanosine Triphosphatase (GTPase) activity were all enhanced in these spheroids compared to control acini. Importantly, inhibition of either FAK or Rho Kinase (ROCK) was sufficient to rescue the polarity defect. We conclude that PDLIM2 expression is essential for feedback regulation of the β1-integrin-RhoA signalling axis and integration of cellular microenvironment signals with gene expression to control the polarity of breast epithelial acini structures. This is a mechanism by which PDLIM2 could mediate tumour suppression in breast epithelium. PMID:24863845

  10. Prostate cancer

    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.

  11. Prostate cancer

    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

  12. Recruitment of focal adhesion kinase and paxillin to β1 integrin promotes cancer cell migration via mitogen activated protein kinase activation

    Integrin-extracellular matrix interactions activate signaling cascades such as mitogen activated protein kinases (MAPK). Integrin binding to extracellular matrix increases tyrosine phosphorylation of focal adhesion kinase (FAK). Inhibition of FAK activity by expression of its carboxyl terminus decreases cell motility, and cells from FAK deficient mice also show reduced migration. Paxillin is a focal adhesion protein which is also phosphorylated on tyrosine. FAK recruitment of paxillin to the cell membrane correlates with Shc phosphorylation and activation of MAPK. Decreased FAK expression inhibits papilloma formation in a mouse skin carcinogenesis model. We previously demonstrated that MAPK activation was required for growth factor induced in vitro migration and invasion by human squamous cell carcinoma (SCC) lines. Adapter protein recruitment to integrin subunits was examined by co-immunoprecipitation in SCC cells attached to type IV collagen or plastic. Stable clones overexpressing FAK or paxillin were created using the lipofection technique. Modified Boyden chambers were used for invasion assays. In the present study, we showed that FAK and paxillin but not Shc are recruited to the β1 integrin cytoplasmic domain following attachment of SCC cells to type IV collagen. Overexpression of either FAK or paxillin stimulated cancer cell migration on type IV collagen and invasion through reconstituted basement membrane which was dependent on MAPK activity. We concluded that recruitment of focal adhesion kinase and paxillin to β1 integrin promoted cancer cell migration via the mitogen activated protein kinase pathway

  13. Discovery, SAR, and Radiolabeling of Halogenated Benzimidazole Carboxamide Antagonists as Useful Tools for (alpha)4(beta)1 Integrin Expressed on T- and B-cell Lymphomas

    Carpenter, R D; Natarajan, A; Lau, E Y; Andrei, M; Solano, D M; Lightstone, F C; DeNardo, S J; Lam, K S; Kurth, M J

    2010-02-08

    The cell surface receptor {alpha}{sub 4}{beta}{sub 1} integrin is an attractive yet poorly understood target for selective diagnosis and treatment of T- and B-cell lymphomas. This report focuses on the rapid microwave preparation of medicinally pertinent benzimidazole heterocycles, structure-activity relationships (SAR) of novel halobenzimidazole carboxamide antagonists 3-6, and preliminary biological evaluation of radioiodinated agents 7, 8, and 18. The I-125 derivative 18 had good tumor uptake (12 {+-} 1% ID/g at 24 h; 4.5 {+-} 1% ID/g at 48 h) and tumor:kidney ratio ({approx}4:1 at 24 h; 2.5:1 at 48 h) in xenograft murine models of B-cell lymphoma. Molecular homology models of {alpha}{sub 4}{beta}{sub 1} integrin have predicted that docked halobenzimidazole carboxamides have the halogen atom in a suitable orientation for halogen-hydrogen bonding. These high affinity ({approx} pM binding) halogenated ligands are attractive tools for medicinal and biological use; the fluoro and iodo derivatives are potential radiodiagnostic ({sup 18}F) or radiotherapeutic ({sup 131}I) agents, whereas the chloro and bromo analogues could provide structural insight into integrin-ligand interactions through photoaffinity cross-linking/mass spectroscopy experiments, as well as co-crystallization X-ray studies.

  14. Recruitment of focal adhesion kinase and paxillin to β1 integrin promotes cancer cell migration via mitogen activated protein kinase activation

    Ohannessian Arthur

    2004-05-01

    Full Text Available Abstract Background Integrin-extracellular matrix interactions activate signaling cascades such as mitogen activated protein kinases (MAPK. Integrin binding to extracellular matrix increases tyrosine phosphorylation of focal adhesion kinase (FAK. Inhibition of FAK activity by expression of its carboxyl terminus decreases cell motility, and cells from FAK deficient mice also show reduced migration. Paxillin is a focal adhesion protein which is also phosphorylated on tyrosine. FAK recruitment of paxillin to the cell membrane correlates with Shc phosphorylation and activation of MAPK. Decreased FAK expression inhibits papilloma formation in a mouse skin carcinogenesis model. We previously demonstrated that MAPK activation was required for growth factor induced in vitro migration and invasion by human squamous cell carcinoma (SCC lines. Methods Adapter protein recruitment to integrin subunits was examined by co-immunoprecipitation in SCC cells attached to type IV collagen or plastic. Stable clones overexpressing FAK or paxillin were created using the lipofection technique. Modified Boyden chambers were used for invasion assays. Results In the present study, we showed that FAK and paxillin but not Shc are recruited to the β1 integrin cytoplasmic domain following attachment of SCC cells to type IV collagen. Overexpression of either FAK or paxillin stimulated cancer cell migration on type IV collagen and invasion through reconstituted basement membrane which was dependent on MAPK activity. Conclusions We concluded that recruitment of focal adhesion kinase and paxillin to β1 integrin promoted cancer cell migration via the mitogen activated protein kinase pathway.

  15. Dietary Cholesterol and Prostate Cancer Risk: Inhibition of prostate Cancer in Rats by the Administration of some Antioxidants

    The present work was carried out to illuminate the relation between high cholesterol diet and incidence of prostate caner. Also, in this study, the effect of DHEA, selenium or oxygen therapy were tested in order to show to what extent they are valid to ameliorate the deleterious effects of prostate cancer. The obtained results revealed that prostate cancer caused a significant (p4 and FT3 were decreased significantly as compared with the corresponding levels in control rats in both normal and high cholesterol diet. Supplementation of DHEA, selenium or oxygen therapy ameliorated all variables recorded herein but, their values did not revert to normal. Any how, the results of this investigation showed that the above mentioned antioxidants possess potential benefits in lessening number of risk factors in blood associated with induced prostate cancer in rats. The underlying mechanisms through which DHEA, selenium and oxygen therapy counteracted prostate cancer were discussed

  16. Prostate brachytherapy

    Implant therapy - prostate cancer; Radioactive seed placement; Internal radiation therapy - prostate; High dose radiation (HDR) ... Brachytherapy takes 30 minutes or more, depending on the type of therapy you have. Before the procedure, ...

  17. Prostate Cancer

    ... 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 ...

  18. Prostate Cancer

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

  19. Prostate biopsy

    ... 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.

  20. Prostatitis - bacterial

    Any bacteria that can cause a urinary tract infection can cause acute bacterial prostatitis. Infections spread through sexual contact can cause prostatitis. These include chlamydia and gonorrhea . Sexually transmitted ...

  1. Chronic prostatitis

    Erickson, Bradley A.; Schaeffer, Anthony J.; Le, Brian

    2008-01-01

    Chronic prostatitis can cause pain and urinary symptoms, and usually occurs without positive bacterial cultures from prostatic secretions (known as chronic abacterial prostatitis or chronic pelvic pain syndrome, CP/CPPS). Bacterial infection can result from urinary tract instrumentation, but the cause and natural history of CP/CPPS are unknown.

  2. Stability of the tumor suppressor merlin depends on its ability to bind paxillin LD3 and associate with β1 integrin and actin at the plasma membrane

    Maria Elisa Manetti

    2012-08-01

    The NF2 gene encodes a tumor suppressor protein known as merlin or schwannomin whose loss of function causes Neurofibromatosis Type 2 (NF2. NF2 is characterized by the development of benign tumors, predominantly schwannomas, in the peripheral nervous system. Merlin links plasma membrane receptors with the actin cytoskeleton and its targeting to the plasma membrane depends on direct binding to the paxillin scaffold protein. Exon 2 of NF2, an exon mutated in NF2 patients and deleted in a mouse model of NF2, encodes the merlin paxillin binding domain (PBD1. Here, we sought to determine the role of PBD1 in regulation of merlin stability and association with plasma membrane receptors and the actin cytoskeleton in Schwann cells. Using a fluorescence-based pulse-chase technique, we measured the half-life of Halo-tagged merlin variants carrying PBD1, exon 2, and exons 2 and 3 deletions in transiently transfected Schwann cells. We found that PBD1 alone was necessary and sufficient to increase merlin's half-life from approximately three to eleven hours. Merlin lacking PBD1 did not form a complex with surface β1 integrins or associate with the actin cytoskeleton. In addition, direct binding studies using purified merlin and paxillin domains revealed that merlin directly binds paxillin LD3 (leucine-aspartate 3 domain as well as the LD4 and LD5 domains. Together these results demonstrate that a direct interaction between merlin PBD1 and the paxillin LD3–5 domains targets merlin to the plasma membrane where it is stabilized by its association with surface β1 integrins and cortical actin.

  3. Influence of reverted austenite on the texture and magnetic properties of 350 maraging steel

    Abreu, Hamilton F.G., E-mail: hamilton@ufc.br [Universidade Federal do Ceará, Campus do Pici-Bloco 729, CEP 60440-554 Fortaleza, CE (Brazil); Silva, Jean J. [Universidade Federal do Ceará, Campus do Pici-Bloco 729, CEP 60440-554 Fortaleza, CE (Brazil); Silva, Manoel R. [Universidade Federal de Itajubá, Campus Sede Itajubá/IFQ- Instituto de Física e Química, Itajubá, MG (Brazil); Gomes da Silva, Marcelo J., E-mail: mgsilva@ufc.br [Universidade Federal do Ceará, Campus do Pici-Bloco 729, CEP 60440-554 Fortaleza, CE (Brazil)

    2015-11-01

    The aging temperature to improve magnetic properties in Maraging-350 steel (Mar-350) is limited by the onset of austenite reversion. The traditional process of cooling after aging is to remove the piece from the oven and then to air cool it. The purpose of this research was to characterize the reverted austenite and to investigate the effect of cooling below the martensite start temperature (M{sub s}) on the magnetic properties. The Mar350 samples aged at temperatures above 550 °C, and subsequently cooled in liquid nitrogen presented less austenite than samples cooled in air, resulting in higher magnetization saturation and a lower coercive force. A combination of optical microscopy (OM), X-ray diffraction (XRD) and electron backscatter diffraction (EBSD) techniques were used to characterize the presence of reverted austenite. The crystallographic texture of both martensite and reverted austenite were analyzed. The texture of the reverted austenite coincides with the texture of the parent austenite indicating that a phenomenon of texture memory is present. - Highlights: • Cooling maraging samples in liquid nitrogen reduces reverted austenite fraction. • Retained austenite increases coercive force and decreases saturation magnetization. • Reverted and parent austenites have the same crystallographic texture. • Memory effect found during reversion transformation.

  4. Influence of reverted austenite on the texture and magnetic properties of 350 maraging steel

    The aging temperature to improve magnetic properties in Maraging-350 steel (Mar-350) is limited by the onset of austenite reversion. The traditional process of cooling after aging is to remove the piece from the oven and then to air cool it. The purpose of this research was to characterize the reverted austenite and to investigate the effect of cooling below the martensite start temperature (Ms) on the magnetic properties. The Mar350 samples aged at temperatures above 550 °C, and subsequently cooled in liquid nitrogen presented less austenite than samples cooled in air, resulting in higher magnetization saturation and a lower coercive force. A combination of optical microscopy (OM), X-ray diffraction (XRD) and electron backscatter diffraction (EBSD) techniques were used to characterize the presence of reverted austenite. The crystallographic texture of both martensite and reverted austenite were analyzed. The texture of the reverted austenite coincides with the texture of the parent austenite indicating that a phenomenon of texture memory is present. - Highlights: • Cooling maraging samples in liquid nitrogen reduces reverted austenite fraction. • Retained austenite increases coercive force and decreases saturation magnetization. • Reverted and parent austenites have the same crystallographic texture. • Memory effect found during reversion transformation

  5. Progress against Prostate Cancer

    ... this page please turn Javascript on. Feature: Prostate Cancer Progress Against Prostate Cancer Past Issues / Winter 2010 Table of Contents ... Read More "Prostate Cancer" Articles Progress Against Prostate Cancer / Prostate Cancer Research Trial Helps John Spencer Treat His ...

  6. Learning about Prostate Cancer

    ... of Information on Prostate Cancer What is prostate cancer? Prostate cancer is the most common cancer in American ... of page Additional Resources of Information on Prostate Cancer Prostate Cancer [nlm.nih.gov] From Medline Plus Medical ...

  7. Stages of Prostate Cancer

    ... Renal Cell) Cancer Leukemia 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 ...

  8. Prostate cancer

    This work is about diagnosis, treatment and monitoring of prostate cancer. The techniques used are: transrectal ultrasound, laparascopy, bone scan, chest x-ray, radiography, chemoterapy and radiotherapy

  9. Isolation and genetic characterization of a fertility-restoring revertant induced from cytoplasmic male sterile rice

    A male fertile revertant was isolated from M1 of a cytoplasmic male sterile indica rice line II-32A, the dry seeds of which were treated with 60Co-γ rays at a dose of 290 Gy. The acquired revertant T24 was morphologically and agronomically similar to II-32B, the maintainer of II-32A. Testcrosses of the revertant with II-32A and Zhenshan 97A showed that the revertant was able to restore the fertility of CMS lines. Genetic analysis of the progenies between T24 and II-32A, Zhenshan 97A XieqingzaoA and DZhenshan 97A, which have different cytoplasms, showed that the fertility restoration of four CMS lines by T24 involved one nuclear gene, indicating that T24 was a result of the mutation of one nuclear gene. The mechanism of the restoration of CMS line by T24 was obviously different from other restorers such as Minghui 63 and 20964, which were shown to behave in two gene mode in fertility restoration. The discovery of the revertant T24 contributes to the understanding of CMS and fertility restoration of CMS in rice. The T24 and its parent II-32A may constitute a pair of near isogenic lines for the restoring gene, which should be valuable materials for molecular genetic analysis of CMS

  10. Revertants of a Transcription Termination Mutant of Yeast Contain Diverse Genetic Alterations

    Kotval, Jeroo; Zaret, Kenneth S.; Consaul, Sandra; Sherman, Fred

    1983-01-01

    Revertants of the cyc1-512 transcription termination mutant of the yeast Saccharomyces cerevisiae were isolated and subjected to a detailed genetic analysis. The cyc1-512 mutation previously was shown to be a 38-base pair deletion that causes only 10% of the normal steady-state levels of CYC1 mRNA and of the CYC1 gene product, iso-1-cytochrome c. Forty-one cyc1-512 revertants were classified by their content of iso-1-cytochrome c and by their genetic properties in meiotic crosses. Many of the...

  11. Blood platelets contain and secrete laminin-8 (alpha4beta1gamma1) and adhere to laminin-8 via alpha6beta1 integrin.

    Geberhiwot, T; Ingerpuu, S; Pedraza, C; Neira, M; Lehto, U; Virtanen, I; Kortesmaa, J; Tryggvason, K; Engvall, E; Patarroyo, M

    1999-12-15

    Laminins, a family of heterotrimeric proteins with cell adhesive/signaling properties, are characteristic components of basement membranes of vasculature and tissues. In the present study, permeabilized platelets were found to react with a monoclonal antibody to laminin gamma1 chain by immunofluorescence. In Western blot analysis of platelet lysates, several monoclonal antibodies to gamma1 and beta1 laminin chains recognized 220- to 230-kDa polypeptides, under reducing conditions, and a structure with much slower electrophoretic mobility under nonreducing conditions. Immunoaffinity purification on a laminin beta1 antibody-Sepharose column yielded polypeptides of 230, 220, 200, and 180 kDa from platelet lysates. In the purified material, mAbs to beta1 and gamma1 reacted with the two larger polypeptides, while affinity-purified rabbit antibodies to laminin alpha4 chain recognized the smallest polypeptide. Identity of the polypeptides was confirmed by microsequencing. One million platelets contained on average 1 ng of laminin (approximately 700 molecules per cell), of which 20-35% was secreted within minutes after stimulation with either thrombin or phorbol ester. Platelets adhered to plastic surfaces coated with the purified platelet laminin, and this process was largely inhibited by antibodies to beta1 and alpha6 integrin chains. We conclude that platelets contain and, following activation, secrete laminin-8 (alpha4beta1gamma1) and that the cells adhere to the protein by using alpha6beta1 integrin. PMID:10585296

  12. Prostate Cancer (Radiation Therapy)

    ... 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 ...

  13. What is Prostate Cancer?

    ... Research Get Involved Find Local ACS Learn About Cancer » Prostate Cancer » Detailed Guide » What is prostate cancer? Share ... how cancers start and spread, see What Is Cancer? Prostate cancer begins when cells in the prostate gland ...

  14. Cryotherapy for prostate cancer

    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 ...

  15. Prostatic melanosis

    Kemal DENİZ

    2007-09-01

    Full Text Available Prostatic melanosis is a rare lesion that is characterized by melanin-containing spindle cells mainly located in the stroma of the prostate gland. This lesion is certainly benign and not a precursor of malignant melanoma. However, differential diagnosis of melanosis with primary and metastatic malignant melanoma is extremely important because of the different biological nature and clinical behavior of these two entities. Recognition of the spectrum of pigmented lesions in the prostate gland is essential to take into consideration of the diagnosis of melanocytic lesions.In this paper, a case of melanosis

  16. Induction of cell scattering by expression of beta1 integrins in beta1-deficient epithelial cells requires activation of members of the rho family of GTPases and downregulation of cadherin and catenin function

    Gimond, C; van Der Flier, A; van Delft, S;

    1999-01-01

    was required for a complete morphological transition towards the spindle-shaped fibroblast-like phenotype. The expression of an interleukin-2 receptor (IL2R)-beta1A chimera and its incorporation into focal adhesions also induced the disruption of cadherin-based adhesions and the reorganization of ECM......Adhesion receptors, which connect cells to each other and to the surrounding extracellular matrix (ECM), play a crucial role in the control of tissue structure and of morphogenesis. In this work, we have studied how intercellular adhesion molecules and beta1 integrins influence each other using two......-catenin protein levels accompanied by their redistribution from the cytoskeleton-associated fraction to the detergent-soluble fraction. Regulation of alpha-catenin protein levels by beta1 integrins is likely to play a role in the morphological transition, since overexpression of alpha-catenin in GE11 cells before...

  17. Ibuprofen reverts antifungal resistance on Candida albicans showing overexpression of CDR genes.

    Ricardo, Elisabete; Costa-de-Oliveira, Sofia; Dias, Ana Silva; Guerra, José; Rodrigues, Acácio Gonçalves; Pina-Vaz, Cidália

    2009-06-01

    Several mechanisms may be associated with Candida albicans resistance to azoles. Ibuprofen was described as being able to revert resistance related to efflux activity in Candida. The aim of this study was to uncover the molecular base of antifungal resistance in C. albicans clinical strains that could be reverted by ibuprofen. Sixty-two clinical isolates and five control strains of C. albicans were studied: the azole susceptibility phenotype was determined according to the Clinical Laboratory for Standards Institute, M27-A2 protocol and minimal inhibitory concentration values were recalculated with ibuprofen (100 microg mL(-1)); synergistic studies between fluconazole and FK506, a Cdr1p inhibitor, were performed using an agar disk diffusion assay and were compared with ibuprofen results. Gene expression was quantified by real-time PCR, with and without ibuprofen, regarding CDR1, CDR2, MDR1, encoding for efflux pumps, and ERG11, encoding for azole target protein. A correlation between susceptibility phenotype and resistance gene expression profiles was determined. Ibuprofen and FK506 showed a clear synergistic effect when combined with fluconazole. Resistant isolates reverting to susceptible after incubation with ibuprofen showed CDR1 and CDR2 overexpression especially of the latter. Conversely, strains that did not revert displayed a remarkable increase in ERG11 expression along with CDR genes. Ibuprofen did not alter resistance gene expression significantly (P>0.05), probably acting as a Cdrp blocker. PMID:19416368

  18. Prostatitis - acute

    ... bladder, such as alcohol, caffeinated foods and drinks, citrus juices, and hot or spicy foods. Drink more ... A.D.A.M. Editorial team. Related MedlinePlus Health Topics Prostate Diseases Browse the Encyclopedia A.D. ...

  19. Prostate cancer

    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....

  20. Prostate cancer

    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....

  1. Adenovirus E1A gene autorepression: revertants of an E1A promoter mutation encode altered E1A proteins

    Larsen, P.L.; Tibbetts, C.

    1987-12-01

    Revertants have been isolated from Ad3hr15, a mutant of human adenovirus type 3 that carries a defective E1A promoter. Transcription of these revertant E1A genes is restored - from nil for Ad3hr15 mutant to levels exceeding that of the wild-type virus. The mutant Ad3hr15 virus and the revertants all have an aberrant E1A promoter that contains two short tandem duplications of viral DNA sequence. The E1A gene-coding region of the mutant is the same as that for wild-type adenovirus type 3, whereas the revertants are characterized by short in-frame deletions within the 5' exon region of their E1A genes. Location of these reverting, second-site deletions is discussed in relation to E1A gene autoregulation and the evolved diversity of E1A-related oncogenic potential among different human adenoviruses.

  2. Fibronectin matrix-mediated cohesion suppresses invasion of prostate cancer cells

    Invasion is an important early step in the metastatic cascade and is the primary cause of death of prostate cancer patients. In order to invade, cells must detach from the primary tumor. Cell-cell and cell-ECM interactions are important regulators of cohesion - a property previously demonstrated to mediate cell detachment and invasion. The studies reported here propose a novel role for α5β1 integrin - the principle mediator of fibronectin matrix assembly (FNMA) - as an invasion suppressor of prostate cancer cells. Using a combination of biophysical and cell biological methods, and well-characterized prostate cancer cell lines of varying invasiveness, we explore the relationship between cohesion, invasiveness, and FNMA. We show that cohesion is inversely proportional to invasive capacity. We also show that more invasive cells express lower levels of α5β1 integrin and lack the capacity for FNMA. Cells were generated to over-express either wild-type α5 integrin or an integrin in which the cytoplasmic domain of α5 was replaced with that of α2. The α2 construct does not promote FNMA. We show that only wild-type α5 integrin promotes aggregate compaction, increases cohesion, and reduces invasion of the more aggressive cells, and that these effects can be blocked by the 70-kDa fibronectin fragment. We propose that restoring capacity for FNMA in deficient cells can increase tumor intercellular cohesion to a point that significantly reduces cell detachment and subsequent invasion. In prostate cancer, this could be of therapeutic benefit by blocking an early key step in the metastatic cascade

  3. Evaluation of the Revertant Phenomenon in Patients with DMD by Immunostaining and Molecular Biology

    Yu Wen; Wu Hua-Chen; Xie Jun; Fan Ji-Shi; Song Yong-Jian; Chen Sheng-Di

    2000-01-01

    Objective To evaluate the significance of revertant phenomenon in patients with Duchunnes muscular dystrophy(DMD). Methods In the present study, the muscles from the patients with DMD were detected by immunofluoresce staining and anti dystrophin antibody, and the 25 pairs of exons in the serum of patients were measured by repetitive PCR test. Results Fifty-one patients had progressive general weakness, especially in proximal and trunk, and hypertrophy calves. Four of them had absent reaction for sarcolemma, which was called as rcvertant phenomenon. The finding was unique and quite rare. The measurement of molecular biology showed no dystrophin deletion in these 4 cases. Conclusions The revertant phenomenon may involve the different mechanism from the conventional medical wisdom. The symptoms and signs of these patients might be improved by a newly therapeutic approach.

  4. ON THE SINGULARITY OF LEAST SQUARES ESTIMATOR FOR MEAN-REVERTING Α-STABLE MOTIONS

    Hu Yaozhong; Long Hongwei

    2009-01-01

    We study the problem of parameter estimation for mean-reverting α-stable motion, dXt= (a0- θ0Xt)dt + dZt, observed at discrete time instants.A least squares estimator is obtained and its asymptotics is discussed in the singular case (a0, θ0)=(0,0).If a0=0, then the mean-reverting α-stable motion becomes Ornstein-Uhlenbeck process and is studied in [7] in the ergodie case θ0 > 0.For the Ornstein-Uhlenbeck process, asymptoties of the least squares estimators for the singular case (θ0 = 0) and for ergodic case (θ0 > 0) are completely different.

  5. Mutation types and aging differently affect revertant fiber expansion in dystrophic mdx and mdx52 mice.

    Yusuke Echigoya

    Full Text Available Duchenne muscular dystrophy (DMD, one of the most common and lethal genetic disorders, and the mdx mouse myopathies are caused by a lack of dystrophin protein. These dystrophic muscles contain sporadic clusters of dystrophin-expressing revertant fibers (RFs, as detected by immunohistochemistry. RFs are known to arise from muscle precursor cells with spontaneous exon skipping (alternative splicing and clonally expand in size with increasing age through the process of muscle degeneration/regeneration. The expansion of revertant clusters is thought to represent the cumulative history of muscle regeneration and proliferation of such precursor cells. However, the precise mechanisms by which RFs arise and expand are poorly understood. Here, to test the effects of mutation types and aging on RF expansion and muscle regeneration, we examined the number of RFs in mdx mice (containing a nonsense mutation in exon 23 and mdx52 mice (containing deletion mutation of exon 52 with the same C57BL/6 background at 2, 6, 12, and 18months of age. Mdx mice displayed a significantly higher number of RFs compared to mdx52 mice in all age groups, suggesting that revertant fiber expansion largely depends on the type of mutation and/or location in the gene. A significant increase in the expression and clustering levels of RFs was found beginning at 6months of age in mdx mice compared with mdx52 mice. In contrast to the significant expansion of RFs with increasing age, the number of centrally nucleated fibers and embryonic myosin heavy chain-positive fibers (indicative of cumulative and current muscle regeneration, respectively decreased with age in both mouse strains. These results suggest that mutation types and aging differently affect revertant fiber expansion in mdx and mdx52 mice.

  6. Non-invasive Brain Stimulation, a Tool to Revert Maladaptive Plasticity in Neuropathic Pain.

    Naro, Antonino; Milardi, Demetrio; Russo, Margherita; Terranova, Carmen; Rizzo, Vincenzo; Cacciola, Alberto; Marino, Silvia; Calabro, Rocco S; Quartarone, Angelo

    2016-01-01

    Neuromodulatory effects of non-invasive brain stimulation (NIBS) have been extensively studied in chronic pain. A hypothetic mechanism of action would be to prevent or revert the ongoing maladaptive plasticity within the pain matrix. In this review, the authors discuss the mechanisms underlying the development of maladaptive plasticity in patients with chronic pain and the putative mechanisms of NIBS in modulating synaptic plasticity in neuropathic pain conditions. PMID:27512368

  7. Has organic farming modernized itself out of business? - Reverting to conventional methods in Denmark

    Kaltoft, Pernille; Risgaard, Marie-Louise

    2005-01-01

    This case study illustrates that reversion to conventional farming does not take place due to technical problems related to production but that farmers in general decided to stop farming organically due to economic problems – primarily marketing problems – and because of changes in regulations. Almost none of the reverters wished to start using pesticides again and most of them also considered organic farming to be a professional challenge. In general, however, organic and conventional produc...

  8. Has organic farming modernised itself out of business? An analysis of reverting organic farmers

    Kaltoft, Pernille; Risgaard, Marie-Louise

    2004-01-01

    In Denmark organic farming presently experiences a recession with 500 organic farmers leaving the organic sector this year (out of a total of 3500 farmers) and a lot more are considering to revert. A range of earlier studies has reported on the process of modernisation of organic farming. Not at least in Denmark where a lot of conventional farmers have converted to the organic mode of production and where conventional/traditional production and distribution channels have adopted a line of org...

  9. Exophytic benign prostatic hyperplasia.

    Blaschko, Sarah D; Eisenberg, Michael L

    2011-08-01

    A 60-year-old man had incidental finding of a multilobular 8 × 7 × 7-cm mass identified posterior to the urinary bladder in continuity with the prostate. The man's prostate-specific antigen was 1.87, and he denied any lower urinary tract symptoms. A transrectal ultrasound-guided biopsy demonstrated benign prostatic tissue. A computed tomography-guided needle aspiration demonstrated a benign epithelium-lined cyst, likely prostatic in origin. Benign prostatic hyperplasia is a proliferation of prostatic epithelial and stromal cells. Although prostatic hyperplasia is usually restricted to the prostate gland, hyperplastic nodules occasionally protrude outside the prostate and rarely form exophytic pelvic masses. PMID:20869104

  10. Simultaneous changes in the function and expression of beta 1 integrins during the growth arrest of poorly differentiated colorectal cells (LISP-1

    R.A. Roela

    2003-08-01

    Full Text Available Cells usually lose adhesion and increase proliferation and migration during malignant transformation. Here, we studied how proliferation can affect the other two characteristics, which ultimately lead to invasion and metastasis. We determined the expression of ß1 integrins, as well as adhesion and migration towards laminin-1, fibronectin, collagens type I and type IV presented by LISP-1 colorectal cancer cells exposed to 2.5% dimethyl sulfoxide (DMSO, an agent capable of decreasing proliferation in this poorly differentiated colorectal cell line. Untreated cells (control, as shown by flow cytometry and monoclonal antibodies, expressed alpha2 (63.8 ± 11.3% positive cells, alpha3 (93.3 ± 7.0%, alpha5 (50.4 ± 12.0% and alpha6 (34.1 ± 4.9% integrins but not alpha1, alpha4, alphav or ß4. Cells adhered well to laminin-1 (73.4 ± 6.0% and fibronectin (40.0 ± 2.0% substrates but very little to collagens. By using blocking monoclonal antibodies, we showed that alpha2, alpha3 and alpha6 mediated laminin-1 adhesion, but neither alpha3 nor alpha5 contributed to fibronectin adherence. DMSO arrested cells at G0/G1 (control: 55.0 ± 2.4% vs DMSO: 70.7 ± 2.5% while simultaneously reducing alpha5 (24.2 ± 19% and alpha6 (14.3 ± 10.8% expression as well as c-myc mRNA (7-fold, the latter shown by Northern blotting. Although the adhesion rate did not change after exposure to DMSO, alpha3 and alpha5 played a major role in laminin-1 and fibronectin adhesion, respectively. Migration towards laminin-1, which was clearly increased upon exposure to DMSO (control: 6 ± 2 cells vs DMSO: 64 ± 6 cells, was blocked by an antibody against alpha6. We conclude that the effects of DMSO on LISP-1 proliferation were accompanied by concurrent changes in the expression and function of integrins, consequently modulating adhesion/migration, and revealing a complex interplay between function/expression and the proliferative state of cells.

  11. Prostate cancer - treatment

    ... 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 ...

  12. Cancer of the Prostate

    ... will die of this disease. Who Gets This Cancer? Prostate cancer occurs only in men, and it is ... Percent of New Cases by Age Group: Prostate Cancer Prostate cancer is most frequently diagnosed among men aged ...

  13. What Is Prostate Cancer?

    Full Text Available ... no such thing as one type of prostate cancer. Prostate cancer is really a spectrum of diseases where on ... very benevolent in its behavior. Men will develop prostate cancer and live the rest of their lives -- 20, ...

  14. Localized Prostate Cancer

    ... a decision aid for men with clinically localized prostate cancer (available at http://effectivehealthcare.ahrq.gov/prostate_da) ... A Decision Aid for Men With Clinically Localized Prostate Cancer Page 1 of 24 Introduction Men with clinically ...

  15. What Is Prostate Cancer?

    Full Text Available ... in their lifetime. Age is the most important risk factor in prostate cancer -- the longer a man ... M.D.: There's no such thing as one type of prostate cancer. Prostate cancer is really a ...

  16. Irradiation and various cytotoxic drugs enhance tyrosine phosphorylation and {beta}{sub 1}-integrin clustering in human A549 lung cancer cells in a substratum-dependent manner in vitro

    Cordes, N.; Beinke, C.; Beuningen, D. van [Inst. of Radiobiology, German Armed Forces, Munich (Germany); Plasswilm, L. [Dept. of Radiation Oncology, Univ. Hospital Basel (Swaziland)

    2004-03-01

    Background and purpose: interactions of cells with a substratum, especially extracellular matrix proteins, initiate clustering of integrin receptors in the cell membrane. This process represents the initial step for the activation of signaling pathways regulating survival, proliferation, differentiation, adhesion, and migration, and could, furthermore, be important for cellular resistance-mediating mechanisms against radiation or cytotoxic drugs. The lack of data elucidating the impact of irradiation or cytotoxic drugs on this important phenomenon led to this study on human A549 lung cancer cells in vitro. Material and methods: the human lung carcinoma cell line A549 grown on polystyrene or fibronectin (FN) was irradiated with 0-8 Gy or treated with cisplatin (0.1-50 {mu}M), paclitaxel (0.1-50 nM), or mitomycin (0.1-50 {mu}M). Colony formation assays, immunofluorescence staining in combination with activation of integrin clustering using anti-{beta}{sub 1}-integrin antibodies (K20), and Western blotting for tyrosine phosphorylation under treatment of cells with the IC{sub 50} for irradiation (2 Gy; IC{sub 50} = 2.2 Gy), cisplatin (2 {mu}M), paclitaxel (5 nM), or mitomycin (7 {mu}M) were performed. Results: attachment of cells to FN resulted in a significantly reduced radio- and chemosensitivity compared to polystyrene. The clustering of {beta}{sub 1}-integrins examined by immunofluorescence staining was only stimulated by irradiation, cisplatin, paclitaxel, or mitomycin in case of cell attachment to FN. By contrast, tyrosine phosphorylation, as one of the major events following {beta}{sub 1}-integrin clustering, showed a 3.7-fold, FN-related enhancement, and treatment of cells with the IC{sub 50} of radiation, cisplatin, paclitaxel, or mitomycin showed a substratum-dependent induction. Conclusion: for the first time, a strong influence of irradiation and a variety of cytotoxic drugs on the clustering of {beta}{sub 1}-integrins could be shown. This event is a

  17. User's guide to REVERT. A CDC 7600 program for converting Spent Fuel Test - Climax data to engineering units, with corrections

    A CDC 7600 computer program, REVERT, can revise Spent Fuel Test - Climax data files using one of several algorithms, depending on the type of data. The algorithms use coefficients from a separate file organized by data type identifiers. REVERT can also make that file of coefficients, using data from tapes made by Hewlett-Packard equipment employed for data acquisition on the spent Fuel Test - Climax at NTS. 12 references

  18. Isolation and characterization of revertants from four different classes of aryl hydrocarbon hydroxylase-deficient hepa-1 mutants.

    Van Gurp, J R; Hankinson, O

    1984-01-01

    Revertants were selected from aryl hydrocarbon hydroxylase (AHH)-deficient recessive mutants belonging to three complementation groups and from a dominant mutant of the Hepa-1 cell line. The recessive mutants had low spontaneous reversion frequencies (less than 4 X 10(-7] that were increased by mutagenesis. The majority of these revertants also had reacquired only partial AHH activity. Revertants of group A mutants were identical to the wild type with respect to both in vivo and in vitro enzyme stability and the Km for the substrate, benzo [alpha]pyrene, and therefore failed to provide evidence that gene A is the AHH structural gene. Group B and group C mutants are defective in the functioning of the Ah receptor required for AHH induction. Revertants of these groups were normal with respect to in vivo temperature sensitivity for AHH induction and for the 50% effective dose for the inducer, 2,3,7,8-tetrachlorodibenzo-p-dioxin, and thus provided no evidence that the B and C genes code for components of the receptor. Two rare group C revertants possessed AHH activity in the absence of induction. The phenotype of one of these was shown to be recessive to the wild type. Spontaneous revertants of the dominant mutant occurred at a frequency 300-fold greater than those of the recessive mutants, and this frequency was not increased by mutagenesis. These revertants all displayed complete restoration of AHH activity to wild type levels. These observations and the results from cell hybridization studies suggest that the dominant revertants arose by a high frequency event leading to functional elimination of the dominant mutation. PMID:6493230

  19. Is financial leverage mean-reverting? Unit root tests and corporate financing models

    M. E. Bontempi; R. Golinelli

    2001-01-01

    In this paper we use the unit root test at both individual company (Dickey-Fuller) and panel (Im-Pesaran-Shin) level, in order to provide some quantitative evidence of the univariate behaviour of Italian companies’ debt-ratio. If it is mean-reverting, then at least a share of companies are going to behave according to the trade-off model, whereas if it is non-stationary, then companies may behave according to pecking order theory. Individual company test results support the pecking order theo...

  20. Revertant seedlings from crown gall tumors retain a portion of the bacterial Ti plasmid DNA sequences*

    Yang, Funmei; Simpson, Robert B.

    1981-01-01

    BT37 is a crown gall teratoma incited on tobacco by Agrobacterium tumefaciens containing pTi-T37, a nopaline-type Ti plasmid. Treatment of this cloned tumor tissue with kinetin at 1 mg/liter results in the formation of relatively normal-appearing shoots. These shoots can be induced to root and set viable seed. In contrast to BT37 tissue, the derived tissues are not phytohormone independent and do not produce nopaline. The reverted plants, like normal tobacco plants, are susceptible to infecti...

  1. Significance of prostatic weight in prostatism

    Jensen, K M; Bruskewitz, R C; Iversen, P; Madsen, P O

    1983-01-01

    In addition to routine evaluation, 68 patients with prostatism underwent blinded urodynamic testing prior to transurethral prostatectomy and were reexamined symptomatologically and urodynamically at 3 and 12 months after surgery to determine if prostatic weight could predict postoperative outcome...

  2. IL-10+ Innate-like B Cells Are Part of the Skin Immune System and Require α4β1 Integrin To Migrate between the Peritoneum and Inflamed Skin.

    Geherin, Skye A; Gómez, Daniela; Glabman, Raisa A; Ruthel, Gordon; Hamann, Alf; Debes, Gudrun F

    2016-03-15

    The skin is an important barrier organ and frequent target of autoimmunity and allergy. In this study, we found innate-like B cells that expressed the anti-inflammatory cytokine IL-10 in the skin of humans and mice. Unexpectedly, innate-like B1 and conventional B2 cells showed differential homing capacities with peritoneal B1 cells preferentially migrating into the inflamed skin of mice. Importantly, the skin-homing B1 cells included IL-10-secreting cells. B1 cell homing into the skin was independent of typical skin-homing trafficking receptors and instead required α4β1-integrin. Moreover, B1 cells constitutively expressed activated β1 integrin and relocated from the peritoneum to the inflamed skin and intestine upon innate stimulation, indicating an inherent propensity to extravasate into inflamed and barrier sites. We conclude that innate-like B cells migrate from central reservoirs into skin, adding an important cell type with regulatory and protective functions to the skin immune system. PMID:26851219

  3. Patient-specific naturally gene-reverted induced pluripotent stem cells in recessive dystrophic epidermolysis bullosa.

    Tolar, Jakub; McGrath, John A; Xia, Lily; Riddle, Megan J; Lees, Chris J; Eide, Cindy; Keene, Douglas R; Liu, Lu; Osborn, Mark J; Lund, Troy C; Blazar, Bruce R; Wagner, John E

    2014-05-01

    Spontaneous reversion of disease-causing mutations has been observed in some genetic disorders. In our clinical observations of severe generalized recessive dystrophic epidermolysis bullosa (RDEB), a currently incurable blistering genodermatosis caused by loss-of-function mutations in COL7A1 that results in a deficit of type VII collagen (C7), we have observed patches of healthy-appearing skin on some individuals. When biopsied, this skin revealed somatic mosaicism resulting in the self-correction of C7 deficiency. We believe this source of cells could represent an opportunity for translational 'natural' gene therapy. We show that revertant RDEB keratinocytes expressing functional C7 can be reprogrammed into induced pluripotent stem cells (iPSCs) and that self-corrected RDEB iPSCs can be induced to differentiate into either epidermal or hematopoietic cell populations. Our results give proof-of-principle that an inexhaustible supply of functional patient-specific revertant cells can be obtained--potentially relevant to local wound therapy and systemic hematopoietic cell transplantation. This technology may also avoid some of the major limitations of other cell therapy strategies, e.g., immune rejection and insertional mutagenesis, which are associated with viral- and nonviral-mediated gene therapy. We believe this approach should be the starting point for autologous cellular therapies using 'natural' gene therapy in RDEB and other diseases. PMID:24317394

  4. Sleep reverts changes in human gray and white matter caused by wake-dependent training.

    Bernardi, Giulio; Cecchetti, Luca; Siclari, Francesca; Buchmann, Andreas; Yu, Xiaoqian; Handjaras, Giacomo; Bellesi, Michele; Ricciardi, Emiliano; Kecskemeti, Steven R; Riedner, Brady A; Alexander, Andrew L; Benca, Ruth M; Ghilardi, M Felice; Pietrini, Pietro; Cirelli, Chiara; Tononi, Giulio

    2016-04-01

    Learning leads to rapid microstructural changes in gray (GM) and white (WM) matter. Do these changes continue to accumulate if task training continues, and can they be reverted by sleep? We addressed these questions by combining structural and diffusion weighted MRI and high-density EEG in 16 subjects studied during the physiological sleep/wake cycle, after 12h and 24h of intense practice in two different tasks, and after post-training sleep. Compared to baseline wake, 12h of training led to a decline in cortical mean diffusivity. The decrease became even more significant after 24h of task practice combined with sleep deprivation. Prolonged practice also resulted in decreased ventricular volume and increased GM and WM subcortical volumes. All changes reverted after recovery sleep. Moreover, these structural alterations predicted cognitive performance at the individual level, suggesting that sleep's ability to counteract performance deficits is linked to its effects on the brain microstructure. The cellular mechanisms that account for the structural effects of sleep are unknown, but they may be linked to its role in promoting the production of cerebrospinal fluid and the decrease in synapse size and strength, as well as to its recently discovered ability to enhance the extracellular space and the clearance of brain metabolites. PMID:26812659

  5. Prostate cancer stem cells

    Tu, Shi-Ming; Lin, Sue-Hwa

    2011-01-01

    Stem cells have long been implicated in prostate glandular 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 AR− status of prostate stem cells renders them inherently insensitive to androgen blockade ther...

  6. Can Prostate Cancer Be Found Early?

    ... Research Get Involved Find Local ACS Learn About Cancer » Prostate Cancer » Detailed Guide » Can prostate cancer be found ... and symptoms of prostate cancer Tests for prostate cancer Prostate cancer stages Survival rates for prostate cancer Previous ...

  7. Interferon-induced revertants of ras-transformed cells: resistance to transformation by specific oncogenes and retransformation by 5-azacytidine.

    Samid, D; Flessate, D M; Friedman, R M

    1987-01-01

    Prolonged alpha/beta interferon (IFN-alpha/beta) treatment of NIH 3T3 cells transformed by a long terminal repeat-activated Ha-ras proto-oncogene resulted in revertants that maintained a nontransformed phenotype long after IFN treatment had been discontinued. Cloned persistent revertants (PRs) produced large amounts of the ras-encoded p21 and were refractile to transformation by EJras DNA and by transforming retroviruses which carried the v-Ha-ras, v-Ki-ras, v-abl, or v-fes oncogene. Transient treatment either in vitro or in vivo with cytidine analogs that alter gene expression by inhibiting DNA methylation resulted in transformation of PR, but not of NIH 3T3, cells. The PR retransformants reverted again with IFN, suggesting that DNA methylation is involved in IFN-induced persistent reversion. Images PMID:2439904

  8. Investigation on the crystallography of the transformation products of reverted austenite in intercritically reheated coarse grained heat affected zone

    Highlights: ► Area of reverted austenite is traced out by crystallographic information. ► Bainite and martensite regions were confirmed within it. ► The martensite region is considered as the blocky MA particles. ► Martensite region has high deformation to initiate fracture. ► More uniform transformation of the reverted austenite is good for toughness. -- Abstract: In present study the intercritically reheated coarse grained heat affected zone (ICCGHAZ) showing the worst impact toughness in the heat affected zone of multi-pass welding was simulated by Gleeble-1500, and its microstructure was investigated in detail by means of scanning electron microscope (SEM) and electron backscattering diffraction (EBSD). With the crystallographic information from EBSD scanning the area of a single reverted austenite grain which formed during the thermal cycles of second pass simulation was traced out. Within it two regions with different characteristic both in morphology and crystallography were found out, showing an un-uniform transformation of the reverted austenite. The region I is a bainitic region containing larger bainitic ferrite grains, while the region II is made up of several clusters containing tiny grains. Based on the crystallographic information each cluster was determined as martensite island thereby should be considered as blocky Martensite/Austenite constituent (M/A), which is hard phase and harmful for toughness. Analysis on the level of deformation shows that the region II is much higher deformed than the region I, indicating there is high stress concentration within the region II. The possible influence of the region I and the region II on fracture is discussed under the early proposed M/A’s fracture-initiating mechanisms. It suggests that the main cause of the toughness reduction is the un-uniform transformation of the reverted austenite, and the toughness performance of the ICCGHAZ could be improved if the transformation of the reverted

  9. Nonlinear Filters for Hidden Markov Models of Regime Change with Fast Mean-Reverting States

    Papanicolaou, Andrew

    2012-01-01

    We consider filtering for a hidden Markov model that evolves with multiple time scales in the hidden states. In particular, we consider the case where one of the states is a scaled Ornstein-Uhlenbeck process with fast reversion to a shifting-mean that is controlled by a continuous time Markov chain modeling regime change. We show that the nonlinear filter for such a process can be approximated by an averaged filter that asymptotically coincides with the true nonlinear filter of the regime-changing Markov chain as the rate of mean reversion approaches infinity. The asymptotics exploit weak converge of the state variables to an invariant distribution, which is significantly different from the strong convergence used to obtain asymptotic results in "Filtering for Fast Mean-Reverting Processes" (19).

  10. [Prostate cancer].

    Morote, Joan; Maldonado, Xavier; Morales-Bárrera, Rafael

    2016-02-01

    The Vall d'Hebron multidisciplinary prostate cancer (PC) team reviews recent advances in the management of this neoplasm. Screening studies with long follow-up show a reduction in mortality, whereas active surveillance is emerging as a therapeutic approach of non-aggressive cancers. New markers increase the specificity of PSA and also allow targeting suspected aggressive cancers. Multiparametric magnetic resonance (mMRI) has emerged as the most effective method in the selection of patients for biopsy and also for local tumor staging. The paradigm of random prostatic biopsy is changing through the fusion techniques that allow guiding ultrasonography-driven biopsy of suspicious areas detected in mMRI. Radical prostatectomy (RP) and radiotherapy (RT) are curative treatments of localized PC and both have experienced significant technological improvements. RP is highly effective and the incorporation of robotic surgery is reducing morbidity. Modern RT allows the possibility of high tumor dose with minimal adjacent dose reducing its toxicity. Androgen deprivation therapy with LHRH analogues remains the treatment of choice for advanced PC, but should be limited to this indication. The loss of bone mass and adverse metabolic effects increases the frequency of fractures and cardiovascular morbimortality. After castration resistance in metastatic disease, new hormone-based drugs have demonstrated efficacy even after chemotherapy resistance. PMID:25727526

  11. Revertant mosaicism in junctional epidermolysis bullosa due to multiple correcting second-site mutations in LAMB3

    Pasmooij, Anna M. G.; Pas, Hendri H.; Bolling, Maria C.; Jonkman, Marcel F

    2007-01-01

    Revertant mosaicism due to in vivo reversion of an inherited mutation has been described in the genetic skin disease epidermolysis bullosa (EB) for the genes KRT14 and COL17A1. Here we demonstrate the presence of multiple second-site mutations, all correcting the germline mutation LAMB3:c.628G→A;p.E210K, in 2 unrelated non-Herlitz junctional EB patients with revertant mosaicism. Both probands had a severe reduction in laminin-332 expression in their affected skin. Remarkably, the skin on the ...

  12. Different Phenotypes in Human Prostate Cancer: α6 or α3 Integrin in Cell-extracellular Adhesion Sites

    Monika Schmelz

    2002-01-01

    Full Text Available The distribution of α6/α3 integrin in adhesion complexes at the basal membrane in human normal and cancer prostate glands was analyzed in 135 biopsies from 61 patients. The levels of the polarized α6/α3 integrin expression at the basal membrane of prostate tumor glands were determined by quantitative immunohistochemistry. The α6/α3 integrin expression was compared with Gleason sum score, pathological stage, and preoperative serum prostate-specific antigen (PSA. The associations were assessed by statistical methods. Eighty percent of the tumors expressed the α6 or α3 integrin and 20% was integrin-negative. Gleason sum score, but not serum PSA, was associated with the integrin expression. Low Gleason sum score correlated with increased integrin expression, high Gleason sum score with low and negative integrin expression. Three prostate tumor phenotypes were distinguished based on differential integrin expression. Type I coexpressed both α6 and α3 subunits, type II exclusively expressed a6 integrin, and type III expressed α3 integrin only. Fifteen cases were further examined for the codistribution of vinculin, paxillin, and CD 151 on frozen serial sections using confocal laser scanning microscopy. The α6/α3 integrins, CD151, paxillin, and vinculin were present within normal glands. In prostate carcinoma, α6 integrin was colocalized with CD 151, but not with vinculin or paxillin. In tumor phenotype I, the α6 subunit did not colocalize with the α3 subunit indicating the existence of two different adhesion complexes. Human prostate tumors display on their cell surface the α6β1 and/or α3β1 integrins. Three tumor phenotypes associated with two different adhesion complexes were identified, suggesting a reorganization of cell adhesion structures in prostate cancer.

  13. Prostate carcinoma

    Prostate cancer is the most common malignancy in men in Europe, North America, and in some African states. Early diagnosis in an asymptomatic stage is possible through the combination of digitorectal examination, PSA serum testing, and systematic biopsy. However, general screening is so far not recommended by the Urologic Societies, because the efficiency is not yet proved. Imaging is also not recommended for first-line screening. Novel functional methods of transrectal ultrasound (TRUS) and endorectal MRI can improve accuracy of tumor detection to more than 90% and can be used for TRUS- and now also MRI-guided biopsy leading to two- to threefold higher tumor detection rates. There is general agreement that all men over 50 years of age should be informed about the possibilities, benefits, and risks of the available methods for early tumor detection. (orig.)

  14. Prostate cancer staging

    ... 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. Prostate cancer screenings

    ... this page: //medlineplus.gov/ency/patientinstructions/000846.htm Prostate cancer screenings To use the sharing features on this ... Intern Med . 2011;155(11):762-71. National Cancer Institute. Prostate Cancer Screening -- for health professionals. Revised April 2, ...

  16. Cryotherapy for prostate cancer

    Cryotherapy uses very cold temperatures to freeze and kill prostate cancer cells. The goal of cryosurgery is ... Possible short-term side effects of cryotherapy for prostate ... of the penis or scrotum Problems controlling your bladder (more ...

  17. What Is Prostate Cancer?

    Full Text Available ... In the United States, one in ten men will develop prostate cancer in their lifetime. Age is ... disease that's very benevolent in its behavior. Men will develop prostate cancer and live the rest of ...

  18. Prostate resection - minimally invasive

    ... microwave thermotherapy; TUMT; BPH - resection; Benign prostatic hyperplasia (hypertrophy) - resection; Prostate - enlarged - resection ... passing an instrument through the opening in your penis (meatus). You will be given general anesthesia (asleep ...

  19. Detecting Prostate Cancer

    Full Text Available ... like to do is just do a rectal examination and feel that prostate. Narrator: The other necessary ... they do have an abnormality in their rectal examination does not mean that they have prostate cancer. ...

  20. What Is Prostate Cancer?

    Full Text Available ... United States, one in ten men will develop prostate cancer in their lifetime. Age is the most important risk factor in prostate cancer -- the longer a man lives the more likely ...

  1. Screening for Prostate Cancer

    ... of Internal Medicine Summaries for Patients Screening for Prostate Cancer: A Guidance Statement From the Clinical Guidelines Committee ... Physicians The full report is titled “Screening for Prostate Cancer: A Guidance Statement From the Clinical Guidelines Committee ...

  2. Detecting Prostate Cancer

    Full Text Available ... such as a trans-rectal ultrasound and a biopsy. Physician: Now, just relax -- the best thing to ... prostate gland. Usually these are accompanied by a biopsy -- a sampling of the prostate tissue with a ...

  3. Prostate Cancer Screening

    ... 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 ...

  4. Prostate Cancer Prevention

    ... prostate cancer increases as men get older. Family history of prostate cancer A man whose father, brother, ... some foods, such as green vegetables, beans and orange juice. Folic acid is a man-made form ...

  5. Enlarged prostate - after care

    BPH - self-care; Benign prostatic hypertrophy - self-care; Benign prostatic hyperplasia - self-care ... exercises ( Kegel exercises ) that strengthen the pelvic floor muscles. Doing these exercise may help with leaking or ...

  6. About the Prostate

    ... DRE) is a useful screening test. Benign prostatic hypertrophy ( BPH ), a non-cancerous prostate condition, typically develops ... Under normal circumstances, the urinary sphincters (bands of muscle at the base of the bladder and at ...

  7. What Is Prostate Cancer?

    Full Text Available ... important risk factor in prostate cancer -- the longer a man lives the more likely he is to ... men confront the reality of prostate cancer on a visit to their urologist. John Bertini, M.D.: ...

  8. Prostate cancer in 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....

  9. Prostate Cancer Foundation

    ... News Faces of Prostate Cancer [4] Survivors Everyday Heroes PCF Researchers Share your story About PCF [1] ... in advanced prostate cancer patients regardless of family history, and are associated with poorer responses to hormonal ...

  10. Can the state of cancer chemotherapy resistance be reverted by epigenetic therapy?

    Duenas-Gonzalez Alfonso

    2006-07-01

    Full Text Available Abstract Background Transcriptome analysis shows that the chemotherapy innate resistance state of tumors is characterized by: poorly dividing tumor cells; an increased DNA repair; an increased drug efflux potential by ABC-transporters; and a dysfunctional ECM. Because chemotherapy resistance involves multiple genes, epigenetic-mediated changes could be the main force responsible of this phenotype. Our hypothesis deals with the potential role of epigenetic therapy for affecting the chemotherapy resistant phenotype of malignant tumors. Presentation of the hypothesis Recent studies reveal the involvement of DNA methylation and histone modifications in the reprogramming of the genome of mammalian cells in cancer. In this sense, it can be hypothesized that epigenetic reprogramming can participate in the establishment of an epigenetic mark associated with the chemotherapy resistant phenotype. If this were correct, then it could be expected that agents targeting DNA methylation and histone deacetylation would by reverting the epigenetic mark induce a global expression profile that mirror the observed in untreated resistant cells. Testing the hypothesis It is proposed to perform a detailed analysis using all the available databases where the gene expression of primary tumors was analyzed and data correlated with the therapeutic outcome to determine whether a transcriptome profiling of "resistance" is observed. Assuming an epigenetic programming determines at some level the intrinsic resistant phenotype, then a similar pattern of gene expression dictated by an epigenetic mark should also be found in cell acquiring drug resistance. If these expectations are meet, then it should be further investigated at the genomic level whether these phenotypes are associated to certain patterns of DNA methylation and chromatin modification. Once confirmed the existence of an epigenetic mark associated to either the intrinsic or acquired chemotherapy resistant phenotype

  11. Energy-Saving Melting and Revert Reduction Technology (E-SMARRT): Final Summary Report

    White, Thornton C [SCRA Appiled R& D

    2014-03-31

    Energy-Saving Melting and Revert Reduction Technology (E-SMARRT) is a balanced portfolio of R&D tasks that address energy-saving opportunities in the metalcasting industry. E-SMARRT was created to: • Improve important capabilities of castings • Reduce carbon footprint of the foundry industry • Develop new job opportunities in manufacturing • Significantly reduce metalcasting process energy consumption and includes R&D in the areas of: • Improvements in Melting Efficiency • Innovative Casting Processes for Yield Improvement/Revert Reduction • Instrumentation and Control Improvement • Material properties for Casting or Tooling Design Improvement The energy savings and process improvements developed under E-SMARRT have been made possible through the unique collaborative structure of the E-SMARRT partnership. The E-SMARRT team consisted of DOE’s Office of Industrial Technology, the three leading metalcasting technical associations in the U.S: the American Foundry Society; the North American Die Casting Association; and the Steel Founders’ Society of America; and SCRA Applied R&D, doing business as the Advanced Technology Institute (ATI), a recognized leader in distributed technology management. This team provided collaborative leadership to a complex industry composed of approximately 2,000 companies, 80% of which employ less than 100 people, and only 4% of which employ more than 250 people. Without collaboration, these new processes and technologies that enable energy efficiencies and environment-friendly improvements would have been slow to develop and had trouble obtaining a broad application. The E-SMARRT R&D tasks featured low-threshold energy efficiency improvements that are attractive to the domestic industry because they do not require major capital investment. The results of this portfolio of projects are significantly reducing metalcasting process energy consumption while improving the important capabilities of metalcastings. Through June

  12. Activation of vanadium nitrogenase expression in Azotobacter vinelandii DJ54 revertant in the presence of molybdenum.

    Lei, S; Pulakat, L; Gavini, N

    2000-09-29

    Azotobacter vinelandii carries three different and genetically distinct nitrogenase systems on its chromosome. Expression of all three nitrogenases is repressed by high concentrations of fixed nitrogen. Expression of individual nitrogenase systems is under the control of specific metal availability. We have isolated a novel type of A. vinelandii DJ54 revertant, designated A. vinelandii BG54, which carries a defined deletion in the nifH gene and is capable of diazotrophic growth in the presence of molybdenum. Inactivation of nifDK has no effect on growth of this mutant strain in nitrogen-free medium suggesting that products of the nif system are not involved in supporting diazotrophic growth of A. vinelandii BG54. Similar to the wild type, A. vinelandii BG54 is also sensitive to 1 mM tungsten. Tn5-B21 mutagenesis to inactivate the genes specific to individual systems revealed that the structural genes for vnf nitrogenase are required for diazotrophic growth of A. vinelandii BG54. Analysis of promoter activity of different nif systems revealed that the vnf promoter is activated in A. vinelandii BG54 in the presence of molybdenum. Based on these data we conclude that A. vinelandii BG54 strain utilizes vnf nitrogenase proteins to support its diazotrophic growth. PMID:11018539

  13. Prostate Cancer: Symptoms, Diagnosis and Treatment

    ... this page please turn Javascript on. Feature: Prostate Cancer Prostate Cancer: Symptoms, Diagnosis and Treatment Past Issues / Winter ... Read More "Prostate Cancer" Articles Progress Against Prostate Cancer / Prostate Cancer Research Trial Helps John Spencer Treat His ...

  14. Co-expression of α9β1 integrin and VEGF-D confers lymphatic metastatic ability to a human breast cancer cell line MDA-MB-468LN.

    Mousumi Majumder

    Full Text Available INTRODUCTION AND OBJECTIVES: Lymphatic metastasis is a common occurrence in human breast cancer, mechanisms remaining poorly understood. MDA-MB-468LN (468LN, a variant of the MDA-MB-468GFP (468GFP human breast cancer cell line, produces extensive lymphatic metastasis in nude mice. 468LN cells differentially express α9β1 integrin, a receptor for lymphangiogenic factors VEGF-C/-D. We explored whether (1 differential production of VEGF-C/-D by 468LN cells provides an autocrine stimulus for cellular motility by interacting with α9β1 and a paracrine stimulus for lymphangiogenesis in vitro as measured with capillary-like tube formation by human lymphatic endothelial cells (HMVEC-dLy; (2 differential expression of α9 also promotes cellular motility/invasiveness by interacting with macrophage derived factors; (3 stable knock-down of VEGF-D or α9 in 468LN cells abrogates lymphangiogenesis and lymphatic metastasis in vivo in nude mice. RESULTS: A comparison of expression of cyclo-oxygenase (COX-2 (a VEGF-C/-D inducer, VEGF-C/-D and their receptors revealed little COX-2 expression by either cells. However, 468LN cells showed differential VEGF-D and α9β1 expression, VEGF-D secretion, proliferative, migratory/invasive capacities, latter functions being stimulated further with VEGF-D. The requirement of α9β1 for native and VEGF-D-stimulated proliferation, migration and Erk activation was demonstrated by treating with α9β1 blocking antibody or knock-down of α9. An autocrine role of VEGF-D in migration was shown by its impairment by silencing VEGF-D and restoration with VEGF-D. 468LN cells and their soluble products stimulated tube formation, migration/invasiveness of HMVEC-dLy cell in a VEGF-D dependent manner as indicated by the loss of stimulation by silencing VEGF-D in 468LN cells. Furthermore, 468LN cells showed α9-dependent stimulation of migration/invasiveness by macrophage products. Finally, capacity for intra-tumoral lymphangiogenesis and

  15. Hormone therapy for prostate cancer

    ... this page: //medlineplus.gov/ency/patientinstructions/000908.htm Hormone therapy for prostate cancer To use the sharing ... helps slow the growth of prostate cancer. Male Hormones and Prostate Cancer Androgens are male sex hormones. ...

  16. 6 Common Cancers - Prostate Cancer

    ... 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 ...

  17. Vaccine Treatment for Prostate Cancer

    ... Preventing and treating prostate cancer spread to bones Vaccine treatment for prostate cancer Sipuleucel-T (Provenge) is ... less advanced prostate cancer. Possible side effects of vaccine treatment Side effects from the vaccine tend to ...

  18. Clinical and demographic features of vertigo: findings from the REVERT registry

    Sam eAgus

    2013-05-01

    Full Text Available IntroductionDespite being a common disease, data on vertigo management in a real-world setting are scarce. AimsTo provide information on the vertigo and its management in a real-world setting.Materials and MethodsData were collected from 4,294 patients with vertigo in 13 countries over 28 months via a multi-national, non-interventional observational study (the so-called REVERT registry. Data included medical history and details of anti-vertigo therapy. ‘Clinical global impression’ (CGI of severity (CGI-S was assessed at baseline (V1 and then at 6 months follow-up (V2 along with CGI change (CGI-C. All variables were analysed descriptively. ResultsThe majority of patients were female, >40 years of age, and almost half had co-morbid cardiovascular disease. Diagnoses were split into 4 categories: 37.2% ‘other vertigo of peripheral vestibular origin’, 26.9% benign paroxysmal positional vertigo (BPPV, 20.5% ‘peripheral vestibular vertigo of unknown origin’ and 15.4% Menière’s disease (MD. Betahistine was the most commonly prescribed therapy prior to and after enrolment, and was followed by piracetam, ginkgo biloba and diuretics. MD had the highest proportion of betahistine treated patients. Almost half of patients were ‘moderately ill’ at V1 based on CGI-S. At V2, patient distribution moved towards ‘less severe illness’ (91.0% improved.The greatest improvements were in the more severely ill, and those with BPPV or ‘other vertigo of peripheral origin’. ConclusionsThere was a reduction in illness severity over the course of the study, some of which is likely to be due to pharmacological intervention. Further studies are needed to confirm these results.

  19. The burden and impact of vertigo: findings from the REVERT patient registry

    Heike eBenecke

    2013-10-01

    Full Text Available Objective: Despite the high prevalence of vertigo globally and an acknowledged, but underreported, effect on an individual’s wellbeing, few studies have evaluated the burden on healthcare systems and society. This study was aimed to quantitatively determine the impact of vertigo on healthcare resource use and work productivity. Methods: The economic burden of vertigo was assessed through a multi-country, non-interventional, observational registry of vertigo patients: the Registry to Evaluate the Burden of Disease in Vertigo (REVERT. Patients included were those with a new diagnosis of Meniere’s disease (MD, benign paroxysmal positional vertigo (BPPV, other vertigo of peripheral vestibular origin or peripheral vestibular vertigo of unknown origin. Results: A total of 4,294 patients at 618 centers in 13 countries were included during the registry. Of the 4,105 patients analyzed, only half were in employment. Among this working patient population, 69.8% had reduced their workload, 63.3% had lost working days and 4.6% had changed and 5.7% had quit their jobs, due to vertigo symptoms. Use of healthcare services among patients was high. In the 3 months preceding Visit 1, patients used emergency services 0.4 ± 0.9 times, primary care consultations 1.6 ± 1.8 times and specialist consultations 1.4 ± 2.0 times (all mean ± SD. A mean of 2.0 ± 5.4 days/patient was also spent in hospital due to vertigo.Conclusions: In addition to the negative impact on the patient from a humanistic perspective, vertigo has considerable impact on work productivity and healthcare resource use.

  20. Promising genomic transfectant into Xeroderma pigmentosum group A with highly amplified mouse DNA and intermediate UV resistance turns revertant

    Following transfection of genomic mouse DNA into an SV40 transformed fibroblast cell line from a patient with Xeroderma pigmentosum (complementation group A, XPA), a single UV resistant cell clone was isolated out of a total of 10(4) independent transfectants. The recipient XPA cell line has as yet not produced spontaneous revertants among 2.2 x 10(8) cells. The isolated cell clone contains 50-70 kb of mouse sequences which are heavily amplified (500-fold), and has acquired both intermediate resistance to UV killing and intermediate unscheduled DNA synthesis (UDS) capacity. By continued passage without selective pressure, cells were generated, which had lost both the dominant marker gene and repetitive mouse sequences. Single colonies of these cells were still intermediately resistant to UV suggesting that either undetected unique mouse DNA had segregated from the bulk of repetitive DNA, or, more likely, that the initially isolated transfectant was a spontaneous revertant. This documents that a persuasive clone isolated can still be a false positive (spontaneous revertant) and that an extremely laborious approach may lead into a dead end

  1. THE DIALECTICS OF HUMANISM AND A POSTMODERN PLAY IN THE WORKS BY A.PEREZ-REVERTE ( THE SIEGE

    Blinova M. P.

    2014-11-01

    Full Text Available The analysis of the philosophical and narrative structure’s features in the novels by modern Spanish writer A. Pérez-Reverte has been reviewed in this article. His works present an example of the postmodern double coding, that is the compound a mass and elite, playing and moral. It allows to avoid the text’s tendentiousness and to keep the content. In the novel “The Siege” A. Pérez-Reverte uses the detective story, but he deconstructs it: keeping the traditional plot’s scheme the writer changes the images’ interpretation, the meaning of the finale, adds the intertext and the conceptual metaphors (the chess, the net, the herbarium. They code some philosophical ideas about human life. At the same time A. Pérez-Reverte asks the traditional classic literature’s questions and shows how war influences the person, what is love and so on. He also makes a psychological analysis of actions’ reasons and reveal the feelings’ contradictory. As a result, the multilayer, nonlinear and metaphorical narrative has been viewed as a particular tool of the author’s opinion realization and the philosophical implication’s creation. And with it the postmodern polysemic text associates with a psychological analysis and humanism

  2. Marine bromophenol bis (2,3-dibromo-4,5-dihydroxy-phenyl)-methane inhibits the proliferation, migration, and invasion of hepatocellular carcinoma cells via modulating β1-integrin/FAK signaling.

    Wu, Ning; Luo, Jiao; Jiang, Bo; Wang, Lijun; Wang, Shuaiyu; Wang, Changhui; Fu, Changqing; Li, Jian; Shi, Dayong

    2015-02-01

    Bis (2,3-dibromo-4,5-dihydroxy-phenyl)-methane (BDDPM) is a natural bromophenol compound derived from marine algae. Previous reports have shown that BDDPM possesses antimicrobial activity. In the present study, we found that BDDPM has cytotoxic activity on a wide range of tumor cells, including BEL-7402 cells (IC50 = 8.7 μg/mL). Further studies have shown that prior to the onset of apoptosis, the BDDPM induces BEL-7402 cell detachment by decreasing the adherence of cells to the extracellular matrix (ECM). Detachment experiments have shown that the treatment of BEL-7402 cells with low concentrations of BDDPM (5.0 μg/mL) significantly inhibits cell adhesion to fibronectin and collagen IV as well as cell migration and invasion. High doses of BDDPM (10.0 μg/mL) completely inhibit the migration of BEL-7402 cells, and the expression level of MMPs (MMP-2 and MMP-9) is significantly decreased. Moreover, the expression of β1-integrin and focal adhesion kinase (FAK) is found to be down-regulated by BDDPM. This study suggests that BDDPM has a potential to be developed as a novel anticancer therapeutic agent due to its anti-metastatic activity and also indicates that BDDPM, which has a unique chemical structure, could serve as a lead compound for rational drug design and for future development of anticancer agents. PMID:25689564

  3. Marine Bromophenol Bis (2,3-Dibromo-4,5-dihydroxy-phenyl-methane Inhibits the Proliferation, Migration, and Invasion of Hepatocellular Carcinoma Cells via Modulating β1-Integrin/FAK Signaling

    Ning Wu

    2015-02-01

    Full Text Available Bis (2,3-dibromo-4,5-dihydroxy-phenyl-methane (BDDPM is a natural bromophenol compound derived from marine algae. Previous reports have shown that BDDPM possesses antimicrobial activity. In the present study, we found that BDDPM has cytotoxic activity on a wide range of tumor cells, including BEL-7402 cells (IC50 = 8.7 μg/mL. Further studies have shown that prior to the onset of apoptosis, the BDDPM induces BEL-7402 cell detachment by decreasing the adherence of cells to the extracellular matrix (ECM. Detachment experiments have shown that the treatment of BEL-7402 cells with low concentrations of BDDPM (5.0 μg/mL significantly inhibits cell adhesion to fibronectin and collagen IV as well as cell migration and invasion. High doses of BDDPM (10.0 μg/mL completely inhibit the migration of BEL-7402 cells, and the expression level of MMPs (MMP-2 and MMP-9 is significantly decreased. Moreover, the expression of β1-integrin and focal adhesion kinase (FAK is found to be down-regulated by BDDPM. This study suggests that BDDPM has a potential to be developed as a novel anticancer therapeutic agent due to its anti-metastatic activity and also indicates that BDDPM, which has a unique chemical structure, could serve as a lead compound for rational drug design and for future development of anticancer agents.

  4. Venom gland EST analysis of the saw-scaled viper, Echis ocellatus, reveals novel alpha9beta1 integrin-binding motifs in venom metalloproteinases and a new group of putative toxins, renin-like aspartic proteases.

    Wagstaff, Simon C; Harrison, Robert A

    2006-08-01

    Echis ocellatus is the most medically important snake in West Africa. However, the composition of its venom and the differential contribution of these venom components to the severe haemorrhagic and coagulopathic pathology of envenoming are poorly understood. To address this situation we assembled a toxin transcriptome based upon 1000 expressed sequence tags (EST) from a cDNA library constructed from pooled venom glands of 10 individual E. ocellatus. We used a variety of bioinformatic tools to construct a fully annotated venom-toxin transcriptome that was interrogated with a combination of BLAST annotation, gene ontology cataloguing and disintegrin-motif searching. The results of these analyses revealed an unusually abundant and diverse expression of snake venom metalloproteinases (SVMP) and a broad toxin-expression profile including several distinct isoforms of bradykinin-potentiating peptides, phospholipase A(2), C-type lectins, serine proteinases and l-amino oxidases. Most significantly, we identified for the first time a conserved alpha(9)beta(1) integrin-binding motif in several SVMPs, and a new group of putative venom toxins, renin-like aspartic proteases. PMID:16713134

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

    Bødker, A; Bruun, J; Balslev, E;

    1999-01-01

    Estrogen receptors (ERs) in the prostate and prostatic urethra were examined in 33 men with benign prostatic hyperplasia (BPH) and in 11 with prostate cancer (PC). The Abbot monoclonal ER-ICA assay was used for immunohistochemical investigation. In the BPH group, ERs were revealed in the prostatic...... stroma in eight cases and in the glandular epithelium in one. In four cases ERs were seen in the prostatic stroma and in the glandular epithelium. In the prostatic urethra, ERs were found in 19 cases located in the urothelium, lamina propria and/or periurethral glands. In the PC group, ERs were...... 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 and...

  6. The experience of using sonoelastography of prostate in prostatic diseases

    P. S. Zubeev

    2014-11-01

    Full Text Available Objective. To assess sonoelastography opportunities in differential diagnosis of prostatic diseases; to place sonoelastography in general algorithm of prostatic diseases diagnostics.Materials and methods. 91 patients under examination were divided into three groups. The first group included 21 patients (23.1 % with suspected prostate carcinoma, later they underwent puncture multifocal biopsy of prostate with morphological verification of prostate carcinoma. The second group consisted of 51 patients (56.0 % with benign prostatic hyperplasia, and in the third group there were 19 patients (20.9 % with acute and chronic prostatitis.Results. 91 patients with different prostatic diseases were examined. There were defined PSA (prostate specific antigen level, and performed TRUS (transrectal ultrasound, biopsy and sonoelastography of prostate. In 72 patients SEG (sonoelastography-picture of prostate was compared to morphological diagnosis. According to SEG findings, 43 (81.1 % patients were revealed to have the areas of reduced compliance due to what malignancy in prostate gland (PG was excluded. Morphological diagnosis of prostate carcinoma was confirmed in 21 patients. In 51 patients SEG-picture corresponded to benign process confirmed by histology.Conclusion. Sonoelastography is a modern diagnostic technique of prostatic diseases, seminal vesicles, paraprostatic space. The distinguished mapping types enable to make differential diagnosis of different prostatic pathological processes. Sonoelastography improves prostate carcinoma diagnostics and staging, and also has economic significance value when compared to MRP (magnetic resonance tomography with bolus contrast.

  7. Prostate-Specific Antigen (PSA) Test

    ... Understanding Laboratory Tests Prostate Cancer—Patient Version Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial Tumor Markers Understanding Prostate Changes: A Health Guide for Men ...

  8. Detecting Prostate Cancer

    Full Text Available ... rectal examination does not mean that they have prostate cancer. It means that we're concerned about it and they should go on to have other tests, such as a trans-rectal ultrasound ... made of the prostate gland. Usually these are accompanied by a biopsy -- ...

  9. Detecting Prostate Cancer

    ... rectal examination does not mean that they have prostate cancer. It means that we're concerned about it and they should go on to have other tests, such as a trans-rectal ultrasound ... made of the prostate gland. Usually these are accompanied by a biopsy -- ...

  10. Optimizing prostate biopsy for repeat transrectal prostate biopsies patients

    Xiaojun Deng; Jianwei Cao; Feng Liu; Weifeng Wang; Jidong Hao; Jiansheng Wan; Hui Liu

    2014-01-01

    Objective:Diagnosis of patients with negative prostate biopsy and persistent suspicion of prostate cancer re-mains a serious problem. In this study, we investigated the application of optimizing prostate biopsy for patients who need repeat prostate biopsy. Methods:In this prospective, non-randomized phase-I clinical trial, the prostate cancer detection rate of initial detection scheme was compared with optimizing prostate biopsy scheme. The number of punctures of initial detection scheme was the same as that of optimizing prostate biopsy scheme. The puncture direction of optimizing prostate biopsy was a 45° angle to the sagittal plane from front, middle, and back. The two cores from each lateral lobe were horizontal y inwardly inclined 45°. Results:A total of 45 patients with initial negative biopsy for cancer were received the optimizing prostate biopsy scheme. The cancer detection rate was 17.8%(8/45), and prostate intraepithelial neoplasm (PIN) was 6.7%(3/45). The pa-tients receiving repeat transrectal prostate biopsies were pathological y diagnosed as lower Gleason grade prostate cancers. Conclusion:The cancer detection rate of repeat biopsy prostate cancer is lower than that of initial biopsy. Our study showed that the optimizing prostate biopsy is important to improve the detection rate of repeat transrectal prostate biopsies patients.

  11. El Club Dumas de Arturo Pérez-Reverte como paradigma de la narrativa posmoderna española

    Isaac Gómez Laguna

    2015-06-01

    Full Text Available El presente artículo ofrece un análisis de los diferentes rasgos posmodernistas que aparecen de manera explícita en El Club Dumas, novela insignia de la narrativa posmoderna en España, en torno a tres ejes centrales: a género de la obra e intertextualidad, b indeterminación e irrealidad, y c individuo y sociedad. Mediante esta reflexión pretendemos evidenciar que su autor, Arturo Pérez-Reverte, no solo crea una novela puramente posmoderna, sino que su obra le sirve para teorizar acerca del posmodernismo.

  12. Prostate cancer; Cancer de la prostate

    Vieillot, S.; Fenoglietto, P.; Ailleres, N.; Hay, M.H.; Dubois, J.B.; Azria, D. [Departement de cancerologie radiotherapie, Universite Montpellier I, CRLC Val d' Aurelle, 34 - Montpellier (France)

    2010-07-01

    Radiation therapy is now widely accepted as an efficacious treatment of localized prostate cancer. The technical developments of recent years have enabled the evolution of a three-dimensional conformal radiotherapy, offering a better adaptation of the dose distribution, and leading therefore to preserve organs at risk. In addition, the required dose delivered to the target volume permit physician to increase the total dose if necessary. This requires a thorough knowledge of the radio-anatomy of the prostate, the natural history of the disease but also the ballistics and dosimetry. The objectives of this work were to detail epidemiology and radio-anatomy of the prostate cancer. In addition, conformal radiation modalities are illustrated by a case report. (authors)

  13. Prostate Cancer Screening (Beyond the Basics)

    ... best in your individual situation. WHAT IS PROSTATE CANCER? — Prostate cancer is a cancer of the prostate, a ... most of them do not die from their cancer. Prostate cancer often grows so slowly that many men ...

  14. What Tests Can Detect Prostate Cancer?

    ... saved articles window. My Saved Articles » My ACS » Prostate Cancer Prevention and Early Detection + - Text Size Download Printable Version [ ... coverage for prostate cancer screening Additional resources for prostate cancer prevention and early detection References: Prostate cancer prevention and ...

  15. Ultrasound- and MRI-Guided Prostate Biopsy

    ... Index A-Z Ultrasound- and MRI-Guided Prostate Biopsy Ultrasound- and MRI-guided prostate biopsy uses imaging ... Biopsy? What is Ultrasound- and MRI-guided Prostate Biopsy? Ultrasound- and MRI-guided prostate biopsies are performed ...

  16. The link between benign prostatic hyperplasia and prostate cancer.

    Ørsted, David D; 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 therapy. Furthermore, risk factors such as prostate inflammation and metabolic disruption have key roles in the development of both diseases. Despite these commonalities, BPH and prostate cancer exhibit important differences in terms of histology and localization. Although large-scale epidemiological studies have shown that men with BPH have an increased risk of prostate cancer and prostate-cancer-related mortality, it remains unclear whether this association reflects a causal link, shared risk factors or pathophysiological mechanisms, or detection bias upon statistical analysis. Establishing BPH as a causal factor for prostate cancer development could improve the accuracy of prognostication and expedite intervention, potentially reducing the number of men who die from prostate cancer. PMID:23165396

  17. The Lifestyle Carbon Dividend: Assessment of the Carbon Sequestration Potential of Grasslands and Pasturelands Reverted to Native Forests

    Rao, S.; Jain, A. K.; Shu, S.

    2015-12-01

    What is the potential of a global transition to a vegan lifestyle to sequester carbon and mitigate climate change? To answer this question, we use an Earth System Model (ESM), the Integrated Science Assessment Model (ISAM). ISAM is a fully coupled biogeochemistry (carbon and nitrogen cycles) and biogeophysics (hydrology and thermal energy) ESM, which calculates carbon sources and sinks due to land cover and land use change activities, such as reforestation and afforestation. We calculate the carbon sequestration potential of grasslands and pasturelands that can be reverted to native forests as 265 GtC on 1.96E+7 km2 of land area, just 41% of the total area of such lands on Earth. The grasslands and pasturelands are assumed to revert back to native forests which existed prior to any human intervention and these include tropical, temperate and boreal forests. The results are validated with above ground regrowth measurements. Since this carbon sequestration potential is greater than the 240 GtC of that has been added to the atmosphere since the industrial era began, it shows that such global lifestyle transitions have tremendous potential to mitigate and even reverse climate change.

  18. Methods for Prostate Biopsy

    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...

  19. Detecting Prostate Cancer

    Full Text Available ... have other tests, such as a trans-rectal ultrasound and a biopsy. Physician: Now, just relax -- the ... exam or PSA test indicates an abnormality, an ultrasound image is made of the prostate gland. Usually ...

  20. Prostate radiation - discharge

    ... day. Avoid orange juice, grapefruit juice, and other citrus juices if they make the bowel or bladder ... A.D.A.M. Editorial team. Related MedlinePlus Health Topics Prostate Cancer Browse the Encyclopedia A.D. ...

  1. What Is Prostate Cancer?

    Full Text Available ... the more likely he is to develop the disease. Physician: Come on back, first room. Narrator: Most ... cancer. Prostate cancer is really a spectrum of diseases where on one end of the spectrum there ...

  2. Detecting Prostate Cancer

    Full Text Available ... have by having their blood sampled and what we look for is a particular glyco-protein that's ... that they have prostate cancer. It means that we're concerned about it and they should go ...

  3. Detecting Prostate Cancer

    Full Text Available ... abnormal and raises the index of suspicion that cancer may be present. Narrator: While the use of ... examination does not mean that they have prostate cancer. It means that we're concerned about it ...

  4. Detecting Prostate Cancer

    Full Text Available ... stands for Prostate Specific Antigen. It is a test that men have by having their blood sampled ... be present. Narrator: While the use of the test remains controversial, a normal PSA level is considered ...

  5. Epigenetics in Prostate Cancer

    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.

  6. Prostate brachytherapy - discharge

    ... into your prostate. They were inserted through your perineum (the area between the scrotum and the anus). ... feel the urge to urinate more often. Your perineum may be tender and bruised. You can use ...

  7. Prostate Cancer Screening

    ... man's bladder that produces fluid for semen. Cancer screening is looking for cancer before you have any ... be easier to treat. There is no standard screening test for prostate cancer. Researchers are studying different ...

  8. Detecting Prostate Cancer

    Full Text Available ... PSA stands for Prostate Specific Antigen. It is a test that men have by having their blood sampled and what we look for is a particular glyco-protein that's found in the blood. ...

  9. Detecting Prostate Cancer

    Full Text Available ... M.D.: PSA stands for Prostate Specific Antigen. It is a test that men have by having ... detection is the digital rectal exam. Barry Trevithick: It doesn't make sense to be afraid of ...

  10. What Is Prostate Cancer?

    Full Text Available ... visit to their urologist. John Bertini, M.D.: It's a wide variety of reasons why they might ... have a prostate. Most men don't pronounce it correctly and wouldn't know where it's located ...

  11. Screening for Prostate Cancer

    ... absolute reduction in mortal- ity. Preliminary results from PIVOT (Prostate Cancer In- tervention Versus Observation Trial), in ... early PSA screening era, prelim- inary findings from PIVOT show that, after 12 years, in- tention to ...

  12. Prostate cancer staging

    ... effects of treatment The chance that treatment can cure your cancer or help you in other ways With stage ... III prostate cancer, the main goal is to cure the cancer by treating it and keeping it from coming ...

  13. Prostatitis - eine endlose Geschichte?

    Riedl CR

    2001-01-01

    Full Text Available Aktuelle epidemiologische Daten aus den USA zeigen, daß der urogenitale Symptomenkomplex, der langläufig als "Prostatitis" bezeichnet wird, ein nicht unbeträchtliches volksgesundheitliches und volkswirtschaftliches Problem darstellt: dieses Krankheitsbild ist jährlich für 2 Millionen Arztbesuche und für 8% aller urologischen Konsulationen in den USA verantwortlich. Umgekehrt sieht jeder Urologe im Jahr zwischen 150 und 250 Patienten mit "Prostatitis".

  14. New Prostate Cancer Treatment Target

    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.

  15. Drugs Approved for Prostate Cancer

    ... Ask about Your Treatment Research Drugs Approved for Prostate Cancer This page lists cancer drugs approved by the ... that are not listed here. Drugs Approved for Prostate Cancer Abiraterone Acetate Bicalutamide Cabazitaxel Casodex (Bicalutamide) Degarelix Docetaxel ...

  16. Understanding Prostate Cancer: Newly Diagnosed

    ... Wellness PCF Spotlight Glossary African American Men Understanding Prostate Cancer Newly Diagnosed Newly Diagnosed Staging the Disease Issues ... you care about has recently been diagnosed with prostate cancer, this section will help guide you through the ...

  17. Multidrug reverting activity toward leukemia cells in a group of new verapamil analogues with low cardiovascular activity

    Biscardi, Monica; Teodori, Elisabetta; Caporale, Roberto;

    2005-01-01

    designed and synthesized to improve their MDR-reverting activity and reduce cardiovascular effects. Cytotoxicity (WST-1 methods) and functional (calcein-acetoxymethyl (Calcein-AM)) assays were performed on a resistant cell line K-562/doxR and on the mononuclear cells (MNCs) of patients with AML...... strongest activity. Results obtained from the MNCs were superimposible to K-562/doxR. Further studies on pump functional analysis confirmed the cytotoxic test results: MM 36, CTS 27 and CTS 41 showed a striking inhibition of P-glycoprotein (Pgp) efflux in K-562/doxR and MNCs. Cardiovascular activity of MM...... 36, CTS 27 and CTS 41, that are the most interesting compounds as MDR inhibitors, followed this course: MM 36>CTS 27>CTS 41, the last one presenting no cardiovascular activity. Chemosensivity to IDA in K-562/doxR cells and AML blasts could be enhanced in vitro by the adjuvant use of the six new VRP...

  18. Methods for Prostate Biopsy

    M. Ghafoori

    2008-01-01

    Full Text Available 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-specific antigen (PSA test is among the best screening tools available in medicine today and is recognized as the best marker for its early detection. Prostate cancers detected by DRE method alone are clinically localized only 50% to 60% of the time, whereas PSA-detected tumors are clinically localized 90% of the time and pathologi-cally confined to the prostate as determined at prostatectomy about two thirds of the time. Recently, the detection of localized prostate cancers has improved, owing to the development of various new biopsy methods. However, a standard biopsy method, including number of cores, has not yet been established at present. When screening results indi-cate the possibility of prostate cancer, a pathologic diagnosis may be pursued by ultrasound guided trans-rectal needle biopsy. Prostate biopsy is usually ad-vised if serum PSA is >4 ng/mL, and this procedure remains the gold standard for prostate cancer diagno-sis. Fine needle biopsy is less painful than core bi-opsy, but also less diagnostically accurate. Systematic biopsy protocols: In 1989, Hodge et al. coined the sextant biopsy method that is still the standard of reference in prostate cancer detection. The prostate is bilaterally divided into three regions (apex, midgland, and base, all of which are system-atically biopsied once. Although Hodge et al. first proposed sextant biopsy under transrectal ultrasound guidance, some recent reports have indicated that systematic sextant biopsy

  19. Genetic epidemiology of prostate cancer

    Wiklund, Fredrik

    2004-01-01

    Prostate cancer is a major health burden throughout the world, yet the etiology of prostate cancer is poorly understood. Evidence has accumulated supporting the existence of a hereditary form of this disease. Improved understanding of the genetic mechanisms underlying the development and progression of prostate cancer would be a major advance for improved prevention, detection and treatment strategies. This thesis evaluates different aspects of the genetic epidemiology of prostate cancer. In ...

  20. Prostate cancer: emerging pharmacotherapeutic modalities

    Pratap Shankar; Anoop Kumar Verma; Rakesh Kumar Dixit; Amod Kumar Sachan

    2013-01-01

    Prostate cancer is the most common cancer in the world due to factors like old age, family history, ethnicity, diet and some elements exposure, with lot of controversies regarding prevention of prostate cancer. Though the exact pathogenesis is not clear, epidemiological evidence supports a relationship between prostate cancer and hormone levels. In this review article we are focusing on the advances in different pharmacotherapeutic modalities i.e. Chemoprevention, Prostate-Specific Antigen, H...

  1. Focal therapy in prostate cancer

    Bos, van den, G.A.M.

    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 prostate cancer may be focally treated followed by careful post-treatment evaluation, and if necessary by focal re-treatment. During the past decades, the age of men at prostate cancer detection has decr...

  2. BPH and prostate cancer risk

    Miah, Saiful; Catto, James

    2014-01-01

    Introduction: With the exclusion of non-melanomatous skin malignancy, prostate cancer (PCa) is the second most prevalent cancer in men globally. It has been reported that the majority of men will develop benign prostatic hyperplasia (BPH) by the time they reach their 60s. Together, these prostatic diseases have a significant morbidity and mortality affecting over a billion men throughout the world. The risk of developing prostate cancer of men suffering BPH is one that has resulted in a healt...

  3. Metastaze raka prostate u penis

    Krpina, Kristian; Markić, Dean; Španjol, Josip; Valenčić, Maksim; Fučkar, Željko

    2011-01-01

    Metastaziranje adenokarcinoma prostate u penis je rijetko. Prikazuje se slučaj adenokarcinoma prostate s metastazama u glans penis. U ovom slučaju metastaze u penis razvile su se devet godina nakon dijagnosticiranja raka prostate s metastazama u regionalne limfne čvorove.

  4. Cholesterol and benign prostate disease.

    Freeman, Michael R; Solomon, Keith R

    2011-01-01

    The origins of benign prostatic diseases, such as benign prostatic hyperplasia (BPH) and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), are poorly understood. Patients suffering from benign prostatic symptoms report a substantially reduced quality of life, and the relationship between benign prostate conditions and prostate cancer is uncertain. Epidemiologic data for BPH and CP/CPPS are limited, however an apparent association between BPH symptoms and cardiovascular disease (CVD) has been consistently reported. The prostate synthesizes and stores large amounts of cholesterol and prostate tissues may be particularly sensitive to perturbations in cholesterol metabolism. Hypercholesterolemia, a major risk factor for CVD, is also a risk factor for BPH. Animal model and clinical trial findings suggest that agents that inhibit cholesterol absorption from the intestine, such as the class of compounds known as polyene macrolides, can reduce prostate gland size and improve lower urinary tract symptoms (LUTS). Observational studies indicate that cholesterol-lowering drugs reduce the risk of aggressive prostate cancer, while prostate cancer cell growth and survival pathways depend in part on cholesterol-sensitive biochemical mechanisms. Here we review the evidence that cholesterol metabolism plays a role in the incidence of benign prostate disease and we highlight possible therapeutic approaches based on this concept. PMID:21862201

  5. Biomarkers for the diagnosis of prostatic inflammation in benign prostatic hyperplasia

    Robert, G.Y.M.; Smit, F.; Hessels, D.; Jannink, S.A.; Karthaus, H.F.M.; Aalders, T.; Jansen, K.; Taille, A. De La; Mulders, P.F.A.; Schalken, J.A.

    2011-01-01

    BACKGROUND: Chronic prostatic inflammation could be a central mechanism in benign prostatic hyperplasia (BPH) progression. Currently, the histological examination of prostate biopsies remains the only way to diagnose prostatic inflammation. Our objective was to find new noninvasive biomarkers for th

  6. Steroid hormone receptors in prostatic hyperplasia and prostatic carcinoma.

    Khalid, B A; Nurshireen, A; Rashidah, M; Zainal, B Y; Roslan, B A; Mahamooth, Z

    1990-06-01

    One hundred and six prostatic tissue samples obtained from transurethral resection were analysed for androgen and estrogen receptors. In 62 of these, progesterone and glucocorticoid receptors were also assayed. Steroid receptors were assayed using single saturation dose 3H-labelled ligand assays. Ninety percent of the 97 prostatic hyperplasia tissues and six of the nine prostatic carcinoma tissues were positive for androgen receptors. Estrogen receptors were only present in 19% and 33% respectively. Progesterone receptors were present in 70% of the tissues, but glucocorticoid receptors were present in only 16% of prostatic hyperplasia and none in prostatic carcinoma. PMID:1725553

  7. Glycogen synthase kinase-3β inhibition depletes the population of prostate cancer stem/progenitor-like cells and attenuates metastatic growth

    Kroon, Jan; in 't Veld, Lars S.; Buijs, Jeroen T.; Cheung, Henry; van der Horst, Geertje; van der Pluijm, Gabri

    2014-01-01

    Cancer cells with stem or progenitor properties play a pivotal role in the initiation, recurrence and metastatic potential of solid tumors, including those of the human prostate. Cancer stem cells are generally more resistant to conventional therapies thus requiring the characterization of key pathways involved in the formation and/or maintenance of this malignant cellular subpopulation. To this end, we identified Glycogen Synthase Kinase-3β (GSK-3β) as a crucial kinase for the maintenance of prostate cancer stem/progenitor-like cells and pharmacologic inhibition of GSK-3β dramatically decreased the size of this cellular subpopulation. This was paralleled by impaired clonogenicity, decreased migratory potential and dramatic morphological changes. In line with our in vitro observations, treatment with a GSK-3β inhibitor leads to a complete loss of tumorigenicity and a decrease in metastatic potential in preclinical in vivo models. These observed anti-tumor effects appear to be largely Wnt-independent as simultaneous Wnt inhibition does not reverse the observed antitumor effects of GSK-3β blockage. We found that GSK-3β activity is linked to cytoskeletal protein F-actin and inhibition of GSK-3β leads to disturbance of F-actin polymerization. This may underlie the dramatic effects of GSK-3β inhibition on prostate cancer migration. Furthermore, GSK-3β inhibition led to strongly decreased expression of several integrin types including the cancer stem cell-associated α2β1 integrin. Taken together, our mechanistic observations highlight the importance of GSK-3β activity in prostate cancer stemness and may facilitate the development of novel therapy for advanced prostate cancer. PMID:25344861

  8. The link between benign prostatic hyperplasia and prostate cancer

    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...... therapy. Furthermore, risk factors such as prostate inflammation and metabolic disruption have key roles in the development of both diseases. Despite these commonalities, BPH and prostate cancer exhibit important differences in terms of histology and localization. Although large-scale epidemiological...... studies have shown that men with BPH have an increased risk of prostate cancer and prostate-cancer-related mortality, it remains unclear whether this association reflects a causal link, shared risk factors or pathophysiological mechanisms, or detection bias upon statistical analysis. Establishing BPH as a...

  9. Osteoporosis and prostate cancer

    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......-specific antigen 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...

  10. Clinical Perspective of Prostate Cancer.

    Patil, Nilesh; Gaitonde, Krishnanath

    2016-06-01

    Prostate cancer is the most common noncutaneous cancer affecting men today. It largely affects men in the fifth and sixth decade of life. Screening for prostate cancer, though controversial, is still the only way to detect early prostate cancer. Multiple newer options such as blood tests and genetic markers are being used in the clinical domain today to improve cancer detection and avoid unnecessary biopsies. To date, biopsy of the prostate remains the only modality to stratify the grade of cancer. Significant improvements in the imaging technology have improved localizing and detecting the disease. Treatment of prostate cancer is stratified on the basis of the grade and volume of the disease. There are multiple treatment options involved in the management of prostate cancer. Treatment of localized prostate cancer still continues to have very high cure rates and long-term cancer-specific survival rates. PMID:27187167

  11. Chemotherapy in Prostate Cancer.

    Hurwitz, Michael

    2015-10-01

    For approximately a decade, chemotherapy has been shown to prolong life in patients with metastatic castration-resistant prostate cancer (mCRPC). Since that time, however, only two agents have proven to prolong life (docetaxel and cabazitaxel). However, in the last year, the addition of chemotherapy to primary hormonal therapy became a standard of care for high-volume castration-sensitive metastatic disease. Here I will review current prostate cancer chemotherapies, mechanisms of resistance to those therapies, and ongoing clinical studies of chemotherapy combinations and novel chemotherapeutics. PMID:26216506

  12. Prostate Cancer Research Trial Helps John Spencer Treat His Cancer

    ... this page please turn Javascript on. Feature: Prostate Cancer Prostate Cancer Research Trial Helps John Spencer Treat His ... Read More "Prostate Cancer" Articles Progress Against Prostate Cancer / Prostate Cancer Research Trial Helps John Spencer Treat His ...

  13. Benign Prostatic Hyperstatic Hyperplasia (BPH) (Beyond the Basics)

    ... names for benign prostatic hyperplasia include benign prostatic hypertrophy, an enlarged prostate, and BPH. BPH occurs only ... prostatic hyperplasia" .) Alpha blockers — These medications relax the muscle of the prostate and bladder neck, which allows ...

  14. Survival in prostate cancer prevention trial detailed

    In the NCI-sponsored Prostate Cancer Prevention Trial, initial findings from a decade ago showed that the drug finasteride significantly reduced the risk of prostate cancer, but among those who did develop prostate cancer, paradoxically, the drug was asso

  15. Prostate Cancer Rates by Race and Ethnicity

    ... HPV-Associated Lung Ovarian Skin Uterine Cancer Home Prostate Cancer Rates by Race and Ethnicity Language: English Español ( ... Tweet Share Compartir The rate of men getting prostate cancer or dying from prostate cancer varies by race ...

  16. Prostate Cancer: Take Time to Decide

    ... PDF for professional printing [PDF-983KB] Cancer Home Prostate Cancer: Take Time to Decide Infographic Language: English Español (Spanish) Recommend on Facebook Tweet Share Compartir Prostate Cancer: Take Time to Decide Most prostate cancers grow ...

  17. Comparability of prostate trials

    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...

  18. Detecting Prostate Cancer

    Full Text Available Roger Babaian, M.D.: PSA stands for Prostate Specific Antigen. It is a test that men have by having their blood sampled and ... testing may be required. Physician: OK, what I'd like to do is just do a rectal ...

  19. Detecting Prostate Cancer

    Full Text Available ... an abnormality in their rectal examination does not mean that they have prostate cancer. It means that we're concerned about it and they ... tissue with a needle. Physician: Now there's a little pressure -- you can probably feel that. Then you' ...

  20. Comparability of prostate trials

    Suciu, S; Sylvester, R; Iversen, P; Christensen, I; Denis, L

    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...

  1. Common Questions About Chronic Prostatitis.

    Holt, James D; Garrett, W Allan; McCurry, Tyler K; Teichman, Joel M H

    2016-02-15

    Chronic prostatitis is relatively common, with a lifetime prevalence of 1.8% to 8.2%. Risk factors include conditions that facilitate introduction of bacteria into the urethra and prostate (which also predispose the patient to urinary tract infections) and conditions that can lead to chronic neuropathic pain. Chronic prostatitis must be differentiated from other causes of chronic pelvic pain, such as interstitial cystitis/bladder pain syndrome and pelvic floor dysfunction; prostate and bladder cancers; benign prostatic hyperplasia; urolithiasis; and other causes of dysuria, urinary frequency, and nocturia. The National Institutes of Health divides prostatitis into four syndromes: acute bacterial prostatitis, chronic bacterial prostatitis (CBP), chronic nonbacterial prostatitis (CNP)/chronic pelvic pain syndrome (CPPS), and asymptomatic inflammatory prostatitis. CBP and CNP/CPPS both lead to pelvic pain and lower urinary tract symptoms. CBP presents as recurrent urinary tract infections with the same organism identified on repeated cultures; it responds to a prolonged course of an antibiotic that adequately penetrates the prostate, if the urine culture suggests sensitivity. If four to six weeks of antibiotic therapy is effective but symptoms recur, another course may be prescribed, perhaps in combination with alpha blockers or nonopioid analgesics. CNP/CPPS, accounting for more than 90% of chronic prostatitis cases, presents as prostatic pain lasting at least three months without consistent culture results. Weak evidence supports the use of alpha blockers, pain medications, and a four- to six-week course of antibiotics for the treatment of CNP/CPPS. Patients may also be referred to a psychologist experienced in managing chronic pain. Experts on this condition recommend a combination of treatments tailored to the patient's phenotypic presentation. Urology referral should be considered when appropriate treatment is ineffective. Additional treatments include pelvic

  2. Prostate brachytherapy in patients with prior evidence of prostatitis

    Purpose: To refute a misconception that a prior history of prostatitis is a contraindication to prostate brachytherapy. Methods and Materials: Five patients with clinical or pathologic evidence of prior prostatitis were treated with transperineal brachytherapy. Four of the patients received a single i.v. dose of ciprofloxacin (500 mg) intraoperatively. Postimplant antibiotics were not given. The pretreatment biopsy slides were reviewed. Results: Two of the five patients developed postimplant urinary retention requiring short-term catheterization, and both resolved spontaneously. One patient developed what appeared to be an exacerbation of his chronic prostatitis. Conclusion: We continue to recommend prostate brachytherapy for the treatment of clinically organ-confined cancer, with no concern about prior clinical or pathologic evidence of prostatitis

  3. Smaller is less stable: Size effects on twinning vs. transformation of reverted austenite in TRIP-maraging steels

    Steels containing reverted nanoscale austenite (γRN) islands or films dispersed in a martensitic matrix show excellent strength, ductility and toughness. The underlying microstructural mechanisms responsible for these improvements are not yet understood, but are observed to be strongly connected to the γRN island or film size. Two main micromechanical effects are conceivable in this context, namely: (i) interaction of γRN with microcracks from the matrix (crack blunting or arresting); and (ii) deformation-induced phase transformation of γRN to martensite (TRIP effect). The focus here is on the latter phenomenon. To investigate size effects on γRN transformation independent of other factors that can influence austenite stability (composition, crystallographic orientation, defect density, surrounding phase, etc.), a model (TRIP-maraging steel) microstructure is designed with support from diffusion simulations (using DICTRA software) to have the same, homogeneous chemical composition in all γRN grains. Characterization is conducted by in-situ tension and bending experiments in conjunction with high-resolution electron backscatter diffraction mapping and scanning electron microscopy imaging, as well as post-mortem transmission electron microscopy and synchrotron X-ray diffraction analysis. Results reveal an unexpected “smaller is less stable” effect due to the size-dependent competition between mechanical twinning and deformation-induced phase transformation

  4. Caloric restriction of db/db mice reverts hepatic steatosis and body weight with divergent hepatic metabolism.

    Kim, Kyung Eun; Jung, Youngae; Min, Soonki; Nam, Miso; Heo, Rok Won; Jeon, Byeong Tak; Song, Dae Hyun; Yi, Chin-Ok; Jeong, Eun Ae; Kim, Hwajin; Kim, Jeonghyun; Jeong, Seon-Yong; Kwak, Woori; Ryu, Do Hyun; Horvath, Tamas L; Roh, Gu Seob; Hwang, Geum-Sook

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is one of the most frequent causes of liver disease and its prevalence is a serious and growing clinical problem. Caloric restriction (CR) is commonly recommended for improvement of obesity-related diseases such as NAFLD. However, the effects of CR on hepatic metabolism remain unknown. We investigated the effects of CR on metabolic dysfunction in the liver of obese diabetic db/db mice. We found that CR of db/db mice reverted insulin resistance, hepatic steatosis, body weight and adiposity to those of db/m mice. (1)H-NMR- and UPLC-QTOF-MS-based metabolite profiling data showed significant metabolic alterations related to lipogenesis, ketogenesis, and inflammation in db/db mice. Moreover, western blot analysis showed that lipogenesis pathway enzymes in the liver of db/db mice were reduced by CR. In addition, CR reversed ketogenesis pathway enzymes and the enhanced autophagy, mitochondrial biogenesis, collagen deposition and endoplasmic reticulum stress in db/db mice. In particular, hepatic inflammation-related proteins including lipocalin-2 in db/db mice were attenuated by CR. Hepatic metabolomic studies yielded multiple pathological mechanisms of NAFLD. Also, these findings showed that CR has a therapeutic effect by attenuating the deleterious effects of obesity and diabetes-induced multiple complications. PMID:27439777

  5. Energy Saving Melting and Revert Reduction Technology (Energy SMARRT): Manufacturing Advanced Engineered Components Using Lost Foam Casting Technology

    Littleton, Harry; Griffin, John

    2011-07-31

    This project was a subtask of Energy Saving Melting and Revert Reduction Technology (Energy SMARRT) Program. Through this project, technologies, such as computer modeling, pattern quality control, casting quality control and marketing tools, were developed to advance the Lost Foam Casting process application and provide greater energy savings. These technologies have improved (1) production efficiency, (2) mechanical properties, and (3) marketability of lost foam castings. All three reduce energy consumption in the metals casting industry. This report summarizes the work done on all tasks in the period of January 1, 2004 through June 30, 2011. Current (2011) annual energy saving estimates based on commercial introduction in 2011 and a market penetration of 97% by 2020 is 5.02 trillion BTU's/year and 6.46 trillion BTU's/year with 100% market penetration by 2023. Along with these energy savings, reduction of scrap and improvement in casting yield will result in a reduction of the environmental emissions associated with the melting and pouring of the metal which will be saved as a result of this technology. The average annual estimate of CO2 reduction per year through 2020 is 0.03 Million Metric Tons of Carbon Equivalent (MM TCE).

  6. MRI diagnosis for prostate cancer

    Recently, in Japan, both the Westernization of life styles and the advent of an aged-society have led to an increase in the incidence of prostate cancer. In making a localizing diagnosis of prostate cancer, magnetic resonance imaging (MRI), which has excellent contrast resolution, and transrectal ultrasonography, are used clinically, and their usefulness is being established. MRI is employed in the diagnosis of prostate cancer to detect tumors, and to determine the stage of such tumors. For the visualization of prostate cancer by MRI, T2-weighted axial images are used exclusively. After becoming familiar with normal prostate images, it is important to evaluate the localization of a tumor, and the invasion of the capsule and seminal vesicles. Future applications of new techniques for MRI will undoubtedly be found. In this paper, the present state of MRI diagnosis of prostate cancer at Kawasaki Medical School Hospital will be reviewed. (author)

  7. MRI diagnosis for prostate cancer

    Tamada, Tsutomu; Nagai, Kiyohisa; Imai, Shigeki; Kajihara, Yasumasa; Jo, Yoshimasa; Tanaka, Hiroyoshi; Fukunaga, Masao (Kawasaki Medical School, Kurashiki, Okayama (Japan)); Matsuki, Takakazu

    1998-01-01

    Recently, in Japan, both the Westernization of life styles and the advent of an aged-society have led to an increase in the incidence of prostate cancer. In making a localizing diagnosis of prostate cancer, magnetic resonance imaging (MRI), which has excellent contrast resolution, and transrectal ultrasonography, are used clinically, and their usefulness is being established. MRI is employed in the diagnosis of prostate cancer to detect tumors, and to determine the stage of such tumors. For the visualization of prostate cancer by MRI, T2-weighted axial images are used exclusively. After becoming familiar with normal prostate images, it is important to evaluate the localization of a tumor, and the invasion of the capsule and seminal vesicles. Future applications of new techniques for MRI will undoubtedly be found. In this paper, the present state of MRI diagnosis of prostate cancer at Kawasaki Medical School Hospital will be reviewed. (author)

  8. MRI diagnosis for prostate cancer

    Tamada, Tsutomu; Nagai, Kiyohisa; Imai, Shigeki; Kajihara, Yasumasa; Jo, Yoshimasa; Tanaka, Hiroyoshi; Fukunaga, Masao [Kawasaki Medical School, Kurashiki, Okayama (Japan); Matsuki, Takakazu

    1998-12-31

    Recently, in Japan, both the Westernization of life styles and the advent of an aged-society have led to an increase in the incidence of prostate cancer. In making a localizing diagnosis of prostate cancer, magnetic resonance imaging (MRI), which has excellent contrast resolution, and transrectal ultrasonography, are used clinically, and their usefulness is being established. MRI is employed in the diagnosis of prostate cancer to detect tumors, and to determine the stage of such tumors. For the visualization of prostate cancer by MRI, T2-weighted axial images are used exclusively. After becoming familiar with normal prostate images, it is important to evaluate the localization of a tumor, and the invasion of the capsule and seminal vesicles. Future applications of new techniques for MRI will undoubtedly be found. In this paper, the present state of MRI diagnosis of prostate cancer at Kawasaki Medical School Hospital will be reviewed. (author)

  9. BENIGN PROSTATIC HYPERPLASIA: UPDATED REVIEW

    Praveen.R

    2013-01-01

    Benign Prostatic Hyperplasia (BPH) is one of the commonest medical conditions affecting the geriatric male population. The enlargement of prostate can lead to various clinical symptoms like difficulty in voiding, urinary retention etc. The symptoms are varied depending on the size of enlargement. The International Prostatic Symptom Score (IPSS) is the gold standard and first step in understanding and diagnosing the disease clinically, but in the recent past there are various other newer tools...

  10. Culture of mouse prostate organoids

    sprotocols

    2014-01-01

    Authors: Chee Wai Chua, Maho Shibata, Ming Lei, Roxanne Toivanen, LaMont Barlow & Michael Shen ### Abstract This protocol describes a novel three-dimensional “organoid” culture for prostate epithelial cells. We describe the digestion and dissociation of prostate tissue into single-cell suspensions containing both prostatic epithelial and stromal cells, the isolation of epithelial cells from the parental population via fluorescence activated cell sorting, and the plating condition...

  11. Prevention strategies in prostate cancer

    Trottier, Greg; Lawrentschuk, N.; Fleshner, N.E.

    2010-01-01

    Prostate cancer (pca) prevention has been an exciting and controversial topic since the results of the Prostate Cancer Prevention Trial (pcpt) were published. With the recently published results of the reduce (Reduction by Dutasteride of Prostate Cancer Events) trial, interest in this topic is at a peak. Primary pca prevention will be unlikely to affect mortality significantly, but the reduction in overtreatment and the effect on quality of life from the avoidance of a cancer diagnosis are im...

  12. Prostatic Stromal Hyperplasia with Atypia

    Hutchinson, Ryan C.; Wu, Kevin J.; Cheville, John C.; Thiel, David D

    2013-01-01

    Prostatic stromal hyperplasia with atypia (PSHA) is a rare histologic finding diagnosed incidentally on prostate biopsies, transurethral resection specimens, and radical prostatectomy specimens. PSHA has a bizarre histologic appearance and these lesions often raise concern for sarcoma; however, their clinical course is indolent and does not include extraprostatic progression. We discuss a case of PHSA discovered on prostate biopsy performed for an abnormal digital rectal examination and revie...

  13. Prostatic Stromal Hyperplasia with Atypia

    Ryan C. Hutchinson

    2013-01-01

    Full Text Available Prostatic stromal hyperplasia with atypia (PSHA is a rare histologic finding diagnosed incidentally on prostate biopsies, transurethral resection specimens, and radical prostatectomy specimens. PSHA has a bizarre histologic appearance and these lesions often raise concern for sarcoma; however, their clinical course is indolent and does not include extraprostatic progression. We discuss a case of PHSA discovered on prostate biopsy performed for an abnormal digital rectal examination and review the literature on this rare pathologic finding.

  14. Neuroendocrine aspects of prostate oncogenesis

    P.V. Glybochko

    2010-03-01

    Full Text Available The prostate cancer is a widespread disease in Russia with high growth rate and high death rate. Active work in discovery of methods of early diagnostics of prostate cancer is carrying out. it will allow to increase considerably the efficiency of treatment. the data on topography, structural and functional organization, physiology and regulatory effect of neuroendocrine cells and neuroendocrine hormones and peptides of prostate produced by neuroendocrine cells are presented in the review. Neuroendocrine mechanisms of development, prospects of early diagnostics and prognosis of prostate cancer are analyzed

  15. Estudio de viabilidad de centro de estética con formación y distribución: Alejandra Revert-Pronails

    Coterillo Ruisánchez, Rodolfo

    2016-01-01

    RESUMEN: En este trabajo se va a realizar un plan de viabilidad, en relación con la empresa “Alejandra Revert – Pronails” para la ampliación de su actividad tras la apertura de un nuevo centro en el municipio de Santa María de Cayón, más concretamente al pueblo de Sarón. La empresa “Alejandra Revert – Pronails” se dedica a la realización de trabajos de estética tales como manicura o maquillaje y a venta de productos cosméticos, para lo que trabaja con una de las mejores marcas actualmente ...

  16. An agent-based approach with collaboration among agents. Estimation of wholesale electricity price on PJM and artificial data generated by a mean reverting model

    This study examines the performance of MAIS (Multi-Agent Intelligent Simulator) equipped with various learning capabilities. In addition to the learning capabilities, the proposed MAIS incorporates collaboration among agents. The proposed MAIS is applied to estimate a dynamic change of wholesale electricity price in PJM (Pennsylvania-New Jersey-Mainland) and an artificial data set generated by a mean reverting model. Using such different types of data sets, the methodological validity of MAIS is confirmed by comparing it with other well-known alternatives in computer science. This study finds that the MAIS needs to incorporate both the mean reverting model and the collaboration behavior among agents in order to enhance its estimation capability. The MAIS discussed in this study will provide research on energy economics with a new numerical capability that can investigate a dynamic change of not only wholesale electricity price but also speculation and learning process of traders. (author)

  17. Acupuncture Treatment of Prostatitis

    HU Jin-sheng

    2010-01-01

    @@ MEDICAL HISTORY A male patient, aged 78, a Hong Kong resident, paid his first visit on October 15, 2007. He complained of frequent urination, 5-6 times at night and once every hour during the daytime, and often with urgent urination and urinary incontinence in the previous 10 months. The patient had been diagnosed by a local hospital as having prostatitis and hyperplasia of the prostate, and he had coronary heart disease treated with Aspirin and other western medicines. As he was getting older, he felt deficient stamina, lassitude, lumbago, feeble lower limbs, pain in the left thigh with restricted motion, preference of local warmness, normal appetite, and powerless defecation once every other day. However, the patient was open-minded with good mental state.

  18. Omega-3 fatty acids partially revert the metabolic gene expression profile induced by long-term calorie restriction.

    López-Domínguez, José Alberto; Cánovas, Ángela; Medrano, Juan F; Islas-Trejo, Alma; Kim, Kyoungmi; Taylor, Sandra L; Villalba, José Manuel; López-Lluch, Guillermo; Navas, Plácido; Ramsey, Jon J

    2016-05-01

    Calorie restriction (CR) consistently extends longevity and delays age-related diseases across several animal models. We have previously shown that different dietary fat sources can modulate life span and mitochondrial ultrastructure, function and membrane fatty acid composition in mice maintained on a 40% CR. In particular, animals consuming lard as the main fat source (CR-Lard) lived longer than CR mice consuming diets with soybean oil (CR-Soy) or fish oil (CR-Fish) as the predominant lipid source. In the present work, a transcriptomic analysis in the liver and skeletal muscle was performed in order to elucidate possible mechanisms underlying the changes in energy metabolism and longevity induced by dietary fat in CR mice. After 8months of CR, transcription downstream of several mediators of inflammation was inhibited in liver. In contrast, proinflammatory signaling was increased in the CR-Fish versus other CR groups. Dietary fish oil induced a gene expression pattern consistent with increased transcriptional regulation by several cytokines (TNF, GM-CSF, TGF-β) and sex hormones when compared to the other CR groups. The CR-Fish also had lower expression of genes involved in fatty acid biosynthesis and increased expression of mitochondrial and peroxisomal fatty acid β-oxidation genes than the other CR diet groups. Our data suggest that a diet high in n-3 PUFA, partially reverts CR-related changes in gene expression of key processes, such as inflammation and steroid hormone signaling, and this may mitigate life span extension with CR in mice consuming diets high in fish oil. PMID:26875793

  19. Association of Symptomatic Benign Prostatic Hyperplasia and Prostate Cancer: Results from the Prostate Cancer Prevention Trial

    Schenk, Jeannette M.; Kristal, Alan R.; Arnold, Kathryn B.; Tangen, Catherine M.; Neuhouser, Marian L; Lin, Daniel W; White, Emily; Thompson, Ian M

    2011-01-01

    This study examined the association between symptomatic benign prostatic hyperplasia (BPH) and prostate cancer risk in 5,068 placebo-arm participants enrolled in the Prostate Cancer Prevention Trial (1993–2003). These data include 1,225 men whose cancer was detected during the 7-year trial—556 detected for cause (following abnormal prostate-specific antigen or digital rectal examination) and 669 detected not for cause (without indication), as well as 3,843 men who had biopsy-proven absence of...

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

    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...

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

    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 with...

  2. Prostate Cancer: All Aspects

    Ahmet Tefekli; Murat Tunc; Volkan Tugcu; Tarık Esen

    2013-01-01

    Hindawi Publishing Corporation The ScientificWorld Journal Volume 2013, Article ID 265234, 2 pages http://dx.doi.org/10.1155/2013/265234 Editorial Prostate Cancer: All Aspects Ahmet Tefekli,1 Murat Tunc,2 Volkan Tugcu,3 and TarJk Esen4 1 Bahcesehir School of Medicine, 34353 Istanbul, Turkey 2 Istanbul School of Medicine, Istanbul University, 34340 Istanbul, Turkey 3Department of Urology, Bakırkoy Training and Research Hospital, 34360 Istanbul, Turkey 4 Koc Univer...

  3. Prostate Focused Ultrasound Therapy.

    Chapelon, Jean-Yves; Rouvière, Olivier; Crouzet, Sébastien; Gelet, Albert

    2016-01-01

    The tremendous progress in engineering and computing power coupled with ultrasound transducer technology and imaging modalities over the past 20 years have encouraged a revival of clinical interest in ultrasound therapy, mainly in High-Intensity Focused Ultrasound (HIFU). So far, the most extensive results from HIFU obtained in urology involve transrectal prostate ablation, which appears to be an effective therapeutic alternative for patients with malignant prostate tumors. Prostate cancer (PCa) is one of the most frequently diagnosed cancers in men. Several treatment options with different therapeutic approaches exist, including HIFU for localized PCa that has been in use for over 15 years. Since the early 2000s, two systems have been marketed for this application, and other devices are currently in clinical trials. HIFU treatment can be used either alone or in combination with (before- or after-) external beam radiotherapy (EBRT) (before or after HIFU) and can be repeated multiple times. HIFU treatment is performed under real-time monitoring with ultrasound or guided by MRI. Two indications are validated today: Primary care treatment and EBRT failure. The results of HIFU for primary care treatment are similar to standard conformal EBRT, even though no randomized comparative studies have been performed and no 10-year follow up data is yet available for HIFU. Salvage HIFU after EBRT failure is increasing with oncological outcomes, similar to those achieved with surgery but with the advantage of fewer adverse effects. HIFU is an evolving technology perfectly adapted for focal treatment. Thus, HIFU focal therapy is another pathway that must be explored when considering the accuracy and reliability for PCa mapping techniques. HIFU would be particularly suited for such a therapy since it is clear that HIFU outcomes and toxicity are relative to the volume of prostate treated. PMID:26486330

  4. Prostate cancer brachytherapy

    The transperineal brachytherapy with 125I/Pd103 seed implantation guided by transurethral ultrasound must be presented as therapeutical option of low urinary morbidity in patients with localized prostate cancer. The combined clinical staging - including Gleason and initial PSA - must be encouraged, for definition of a group of low risk and indication of exclusive brachytherapy. Random prospective studies are necessary in order to define the best role of brachytherapy, surgery and external beam radiation therapy

  5. Chemotherapeutic prevention studies of prostate cancer

    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....

  6. Prevention and early detection of prostate cancer

    Cuzick, J.; Thorat, M.A.; Andriole, G.; Brawley, O.W.; Brown, P.H.; Culig, Z.; Eeles, R.A.; Ford, L.G.; Hamdy, F.C.; Holmberg, L.; Ilic, D.; Key, T.J.; Vecchia, C. La; Lilja, H.; Marberger, M.; Meyskens, F.L.; Minasian, L.M.; Parker, C.; Parnes, H.L.; Perner, S.; Rittenhouse, H.; Schalken, J.A.; Schmid, H.P.; Schmitz-Drager, B.J.; Schroder, F.H.; Stenzl, A.; Tombal, B.; Wilt, T.J.; Wolk, A.

    2014-01-01

    Prostate cancer is a common malignancy in men and the worldwide burden of this disease is rising. Lifestyle modifications such as smoking cessation, exercise, and weight control offer opportunities to reduce the risk of developing prostate cancer. Early detection of prostate cancer by prostate-speci

  7. Chemotherapeutic prevention studies of prostate cancer

    Djavan, Bob; Zlotta, Alexandre; Schulman, Claude; Teillac, Pierre; Iversen, Peter; Boccon Gibod, Laurent; Bartsch, Georg; Marberger, Michael

    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....

  8. HUMAN PROSTATE CANCER RISK FACTORS

    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...

  9. Biomarkers in Prostate Cancer Epidemiology

    Mudit Verma

    2011-09-01

    Full Text Available Understanding the etiology of a disease such as prostate cancer may help in identifying populations at high risk, timely intervention of the disease, and proper treatment. Biomarkers, along with exposure history and clinical data, are useful tools to achieve these goals. Individual risk and population incidence of prostate cancer result from the intervention of genetic susceptibility and exposure. Biochemical, epigenetic, genetic, and imaging biomarkers are used to identify people at high risk for developing prostate cancer. In cancer epidemiology, epigenetic biomarkers offer advantages over other types of biomarkers because they are expressed against a person’s genetic background and environmental exposure, and because abnormal events occur early in cancer development, which includes several epigenetic alterations in cancer cells. This article describes different biomarkers that have potential use in studying the epidemiology of prostate cancer. We also discuss the characteristics of an ideal biomarker for prostate cancer, and technologies utilized for biomarker assays. Among epigenetic biomarkers, most reports indicate GSTP1 hypermethylation as the diagnostic marker for prostate cancer; however, NKX2-5, CLSTN1, SPOCK2, SLC16A12, DPYS, and NSE1 also have been reported to be regulated by methylation mechanisms in prostate cancer. Current challenges in utilization of biomarkers in prostate cancer diagnosis and epidemiologic studies and potential solutions also are discussed.

  10. Human Prostate Cancer Hallmarks Map.

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

    2016-01-01

    Human prostate cancer is a complex heterogeneous disease that mainly affects elder male population of the western world with a high rate of mortality. Acquisitions of diverse sets of hallmark capabilities along with an aberrant functioning of androgen receptor signaling are the central driving forces behind prostatic tumorigenesis and its transition into metastatic castration resistant disease. These hallmark capabilities arise due to an intense orchestration of several crucial factors, including deregulation of vital cell physiological processes, inactivation of tumor suppressive activity and disruption of prostate gland specific cellular homeostasis. The molecular complexity and redundancy of oncoproteins signaling in prostate cancer demands for concurrent inhibition of multiple hallmark associated pathways. By an extensive manual curation of the published biomedical literature, we have developed Human Prostate Cancer Hallmarks Map (HPCHM), an onco-functional atlas of human prostate cancer associated signaling and events. It explores molecular architecture of prostate cancer signaling at various levels, namely key protein components, molecular connectivity map, oncogenic signaling pathway map, pathway based functional connectivity map etc. Here, we briefly represent the systems level understanding of the molecular mechanisms associated with prostate tumorigenesis by considering each and individual molecular and cell biological events of this disease process. PMID:27476486

  11. ESUR prostate MR guidelines 2012

    Barentsz, Jelle O; Richenberg, Jonathan; Clements, Richard; Choyke, Peter; Verma, Sadhna; Villeirs, Geert; Rouviere, Olivier; Logager, Vibeke; Fütterer, Jurgen J

    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...

  12. Vitamin E and Prostate Cancer

    Vitamin E, its metabolites or its analogs, might help prevent prostate cancer initiation or progression. Prostate cancer is the most common non-skin malignancy and the second leading cause of cancer deaths among men in the United States, exceeded only by lung cancer. About 218,890 new cases of prost...

  13. Androgen Control in Prostate Cancer.

    Pelekanou, Vasiliki; Castanas, Elias

    2016-10-01

    Research on prostate cancer has extensively advanced in the past decade, through an improved understanding for its genetic basis and risk-stratification. Molecular classification of prostate cancer into distinct subtypes and the recognition of new histologic entities promise the development of tailored-made management strategies of patients. Nowadays, various alternatives are available for clinical management of localized disease ranging from observation alone through radical prostatectomy. In patients with castration-resistant prostate cancer, the approval of new drugs for the management of metastatic disease has offered promising results improving the survival of these patients. In this context, androgen receptors (AR) remain at the epicenter of prostate cancer research holding a prominent role in the biology and therapeutic regimens of prostate cancer. As many of castration-resistant tumors retain hormone-responsiveness, AR is a clinical relevant, druggable target. However, AR paradoxically remains neglected as a prostate cancer biomarker. The great advancements in prostate cancer preclinical and clinical research, imply further improvement in clinical and translational data, for patient selection and treatment optimization. For a precision medicine-guided clinical management of prostate cancer, AR evaluation has to be implemented in companion and complementary diagnostics, as discussed here. J. Cell. Biochem. 117: 2224-2234, 2016. © 2016 Wiley Periodicals, Inc. PMID:27104784

  14. Effect of Obesity on Prostate-Specific Antigen, Prostate Volume, and International Prostate Symptom Score in Patients with Benign Prostatic Hyperplasia

    Kim, Jong Min; Song, Phil Hyun; Kim, Hyun Tae; Moon, Ki Hak

    2011-01-01

    Purpose We examined the correlation between body mass index (BMI) as a marker of obesity and prostate-specific antigen (PSA), prostate volume (PV), and International Prostate Symptom Score (IPSS) in patients with benign prostatic hyperplasia (BPH). Materials and Methods From January 2008 to December 2008, we examined 258 patients diagnosed with BPH. Patients taking 5α-reductase inhibitors or those diagnosed with prostate cancer were excluded from this study. BPH was defined as PV≥25 ml and IP...

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

    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.

  16. Role of transurethral resection of the prostate in the management of prostate cancer

    Szollosi Attila; Martha Orsolya; Denes Lorand; Vida Arpad Oliver; Maier Adrian; Pavai Zoltan

    2016-01-01

    Introduction: Prostate cancer is the second most diagnosed cancer in men, after lung cancer. The gold standard procedure in prostate cancer (PCa) diagnosis is the ultrasound guided prostate biopsy. Transurethral resection of the prostate (TURP) used in solving the bladder outlet obstruction, can have a role in detection of PCa. The aim of this retrospective study is to examine the role of transurethral resection of the prostate in the diagnosis and therapy of prostate cancer.

  17. Role of transurethral resection of the prostate in the management of prostate cancer

    Szollosi Attila

    2016-06-01

    Full Text Available Introduction: Prostate cancer is the second most diagnosed cancer in men, after lung cancer. The gold standard procedure in prostate cancer (PCa diagnosis is the ultrasound guided prostate biopsy. Transurethral resection of the prostate (TURP used in solving the bladder outlet obstruction, can have a role in detection of PCa. The aim of this retrospective study is to examine the role of transurethral resection of the prostate in the diagnosis and therapy of prostate cancer.

  18. Chromosome 17p13.2 transfer reverts transformation phenotypes and Fas-mediated apoptosis in breast epithelial cells.

    Lareef, Mohamed H; Tahin, Quivo; Song, Joon; Russo, Irma H; Mihaila, Dana; Slater, Carolyn M; Balsara, Binaifer; Testa, Joseph R; Broccoli, Dominique; Grobelny, Jennifer V; Mor, Gil; Cuthbert, Andrew; Russo, Jose

    2004-04-01

    Transformation of the human breast epithelial cells (HBEC) MCF-10F with the carcinogen benz(a)pyrene (BP) into BP1-E cells resulted in the loss of the chromosome 17 p13.2 locus (D17S796 marker) and formation of colonies in agar-methocel (colony efficiency (CE)), loss of ductulogenic capacity in collagen matrix, and resistance to anti-Fas monoclonal antibody (Mab)-induced apoptosis. For testing the role of that specific region of chromosome 17 in the expression of transformation phenotypes, we transferred chromosome 17 from mouse fibroblast donors to BP1-E cells. Chromosome 11 was used as negative control. After G418 selection, nine clones each were randomly selected from BP1-E-11neo and BP1-E-17neo hybrids, respectively, and tested for the presence of the donor chromosomes by fluorescent in situ hybridization and polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) analyses. Sensitivity to Fas Mab-induced apoptosis and evaluation of transformation phenotype expression were tested in MCF-10F, BP1-E, and nine BP1-E-11neo and BP1-E-17neo clones each. Six BP1-E-17neo clones exhibited a reversion of transformation phenotypes and a dose dependent sensitivity to Fas Mab-induced apoptosis, behaving similarly to MCF-10F cells. All BP1-E-11neo, and three BP1-E-17neo cell clones, like BP1-E cells, retained a high CE, loss of ductulogenic capacity, and were resistant to all Fas Mab doses tested. Genomic analysis revealed that those six BP1-E-17neo clones that were Fas-sensitive and reverted their transformed phenotypes had retained the 17p13.2 (D17S796 marker) region, whereas it was absent in all resistant clones, indicating that the expression of transformation phenotypes and the sensitivity of the cells to Fas-mediated apoptosis were under the control of genes located in this region. PMID:15057875

  19. American Cancer Society Recommendations for Prostate Cancer Early Detection

    ... saved articles window. My Saved Articles » My ACS » Prostate Cancer Prevention and Early Detection + - Text Size Download Printable Version [ ... coverage for prostate cancer screening Additional resources for prostate cancer prevention and early detection References: Prostate cancer prevention and ...

  20. A Prospective Randomized Trial of Two Different Prostate Biopsy Schemes

    2016-07-03

    Prostate Cancer; Local Anesthesia; Prostate-Specific Antigen/Blood; Biopsy/Methods; Image-guided Biopsy/Methods; Prostatic Neoplasms/Diagnosis; Prostate/Pathology; Prospective Studies; Humans; Male; Ultrasonography, Interventional/Methods

  1. Radium-223 Improves Survival in Patients with Advanced Prostate Cancer

    ... and data sets for researchers Research by Cancer Type Find research about a specific cancer type Progress Annual Report ... Laws Careers Visitor Information Search Search Home Cancer Types Prostate Cancer Research Prostate Cancer Patient Prostate Cancer Treatment Prostate Cancer ...

  2. A histological study of prostate

    Ashfaq U. Hassan

    2013-08-01

    Full Text Available The work of anatomists and pathologists in the role of study of prostate has been significant. Starting from earlier times till modern time, the study of prostate has been a dynamic one and the basic anatomical knowledge of the prostate has undergone much change apart from the new techniques, micro invasive procedures and the chemotherapeutic approach for various disorders of the gland. The present study was based on the microscopic examination of Prostatic tissue of individuals with individual tissues of different age groups. The present study involved 40 cases which were further subdivided into various age groups and characteristic histological changes were noted. The study presents an assessment of age changes in prostate in elderly in Kashmiri population with pathological significance. Besides the histological study is of great importance in staging of diseases of prostate and especially in modern era where the incidence and prevalence of prostatic diseases is on rise. [Int J Res Med Sci 2013; 1(4.000: 557-562

  3. Diagnostic imaging of the prostate

    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

  4. Decreased expression of the amplified mdr1 gene in revertants of multidrug-resistant human myelogenous leukemia K562 occurs without loss of amplified DNA.

    Sugimoto, Y.; Roninson, I B; Tsuruo, T.

    1987-01-01

    Amplification and increased expression of the mdr1 gene associated with multidrug resistance in human tumors were found in multidrug-resistant sublines of human myelogenous leukemia K562 selected with vincristine (K562/VCR) or adriamycin (K562/ADM). In two revertant cell lines of K562/ADM, amplification of the mdr1 gene was maintained at the same level as in K562/ADM, but expression of the 4.5-kilobase mdr1 mRNA was greatly decreased, indicating that amplified genes may be inactivated at the ...

  5. Oxidative stress in prostate hyperplasia and carcinogenesis.

    Udensi, Udensi K; Tchounwou, Paul B

    2016-01-01

    Prostatic hyperplasia (PH) is a common urologic disease that affects mostly elderly men. PH can be classified as benign prostatic hyperplasia (BPH), or prostate cancer (PCa) based on its severity. Oxidative stress (OS) is known to influence the activities of inflammatory mediators and other cellular processes involved in the initiation, promotion and progression of human neoplasms including prostate cancer. Scientific evidence also suggests that micronutrient supplementation may restore the antioxidant status and hence improve the clinical outcomes for patients with BPH and PCa. This review highlights the recent studies on prostate hyperplasia and carcinogenesis, and examines the role of OS on the molecular pathology of prostate cancer progression and treatment. PMID:27609145

  6. Potassium channels in prostate and colonic cancer

    Ousingsawat, Jiraporn

    2007-01-01

    Large conductance Ca2+-activated K+ channels in human prostate cancer The KCNMA1 gene encoding the alpha-subunit of BK channels is amplified and BK channel expression is enhanced in late-stage, metastatic and hormone-refractory human prostate cancer tissues, whereas benign prostate tissues show only a weak expression of BK channels. PC-3 hormone-insensitive prostate cancer cells, but not hormone-sensitive prostate cancer cells (LNCaP) and benign prostate hyperplasia cells (BPH-1), show an ...

  7. An unusually large leiomyoma of the prostate.

    Kapp, Brian; Abarzua-Cabezas, Fernando; Cusano, Antonio; Meraney, Anoop

    2014-02-01

    Prostate leiomyomas are benign mesenchymal smooth muscle tumors devoid of glandular elements within the prostate or juxta-prostatic position. Leiomyomas develop in organs containing smooth muscle, including the kidney, bladder and seminal vesicle. Prostate leiomyomas are either a pure form or associated with benign prostate hyperplasia, and diagnosis is challenging, with definitive identification relying on pathology. However, imaging techniques, such as MRI, have proven to be useful diagnostic tools. We report on a 57-year-old male with lower urinary tract symptomatology who was diagnosed with a large prostate leiomyoma and underwent an open radical cystoprostatectomy and ileal conduit urinary diversion. PMID:24529022

  8. Prostate resonance imaging: morphology and metabolism

    The cancer of prostate is the most frequent neoplasms and the third cause of death in men, although the average of survival of patients it improved, the cancer of prostate is an important problem in health. The majority of these tumors are of slow growth and the early detection allows high probabilities of definitive treatment. The neoplasms of prostate detected at present are smaller than the detected ones 20 years ago behind, nevertheless exist big differences in the aggressiveness of these tumors. The images are very important in the management of prostate cancer, and the magnetic resonance imaging of the prostate is a new tool in the evaluation of prostate cancer

  9. 6 Common Cancers - Prostate Cancer

    ... PSA tests. Read More "6 Common Cancers" Articles Lung Cancer / Breast Cancer / Prostate Cancer / Colorectal Cancer / Skin Cancer / Gynecologic Cancers Spring 2007 Issue: Volume 2 Number 2 Page 10 MedlinePlus | Subscribe | Magazine Information | Contact Us | Viewers & ...

  10. Neuroendocrine differentiation in prostate cancer

    Jiaoti Huang

    2008-01-01

    @@ The treatment of choice for advanced/metastatic prostate cancer(PC) is hormonal therapy. Although patients respond initially to this therapy, the tumor will recur and enter the androgen-independent state, which is the major obstacle in therapy.

  11. Prostate resection - minimally invasive - discharge

    ... a burning sensation when you urinate, fever, or chills). Your urine stream is not as strong, or ... pubmed/23234640 . Roehrborn CG. Benign prostatic hyperplasia: Etiology, pathophysiology, epidemiology, and natural history. In: Wein AJ, Kavoussi ...

  12. Contemporary Management of Prostate Cancer.

    Cotter, Katherine; Konety, Badrinath; Ordonez, Maria A

    2016-01-01

    Prostate cancer represents a spectrum ranging from low-grade, localized tumors to devastating metastatic disease. We discuss the general options for treatment and recent developments in the field. PMID:26949522

  13. Multidrug Resistance in Prostate Cancer

    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

  14. Treatment Option Overview (Prostate Cancer)

    ... This procedure is done to treat benign prostatic hypertrophy and it is sometimes done to relieve symptoms ... or part of the small intestine through weak muscles into the groin ). Inguinal hernia may occur more ...

  15. Rectal function following prostate brachytherapy

    Purpose: Quality of life following therapeutic intervention for carcinoma of the prostate gland has not been well documented. In particular, a paucity of data has been published regarding bowel function following prostate brachytherapy. This study evaluated late bowel function in 209 consecutive prostate brachytherapy patients via a one-time questionnaire administered 16-55 months postimplant. Materials and Methods: Two hundred nineteen consecutive patients underwent permanent prostate brachytherapy from April 1995 through February 1998 using either 125I or 103Pd for clinical T1c-T3a carcinoma of the prostate gland. Of the 219 patients, 7 had expired. Of the remaining 212 patients (median follow-up, 28 months), each patient was mailed a self-administered questionnaire (10 questions) with a prestamped return envelope; 209 (98.6%) surveys were returned. Clinical parameters evaluated for bowel dysfunction included patient age, diabetes, hypertension, history of tobacco consumption, clinical T-stage, elapsed time since implant, and prostate ultrasound volume. Treatment parameters included utilization of neoadjuvant hormonal manipulation, utilization of moderate dose external beam radiation therapy prior to implantation, choice of isotope (125I vs. 103Pd), rectal dose (average, median and maximum doses), total implanted seed strength, values of the minimum dose received by 90% of the prostate gland (D90), and the percent prostate volume receiving 100%, 150%, and 200% of the prescribed minimum peripheral dose (V100, V150 and V200, respectively). Because detailed baseline bowel function was not available for these patients, a cross-sectional survey was performed in which 30 newly diagnosed prostate cancer patients of comparable demographics served as controls. Results: The total rectal function scores for the brachytherapy and control patients were 4.3 and 1.6, respectively, out of a total 27 points (p 103Pd resulted in lower radiation doses to the rectum, the choice of

  16. Prostate cancer stem cell biology

    Yu, Chunyan; Yao, Zhi; Jiang, Yuan; Keller, Evan T.

    2012-01-01

    The cancer stem cell (CSC) model provides insights into pathophysiology of cancers and their therapeutic response. The CSC model has been both controversial, yet provides a foundation to explore cancer biology. In this review, we provide an overview of CSC concepts, biology and potential therapeutic avenues. We then focus on prostate CSC including (1) their purported origin as either basal-derived or luminal-derived cells; (2) markers used for prostate CSC identification; (3) alterations of s...

  17. Perceived causes of prostate cancer among prostate cancer survivors in the 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,

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

    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.

  19. Percutaneous prostatic arterial embolization for the treatment of benign prostatic hyperplasia

    Percutaneous prostatic artery embolization (PAE) is a kind of technology that can treat benign prostatic hyperplasia through embolizing bilateral prostatic arteries to obstruct most blood supply to the prostate thus to cause prostatic tissue necrosis and the volume reduction of the prostate, resulting in the improvement of the clinical symptoms. This technique is technically simple, clinically convenient and well repeatable. This article aims to make a special comment about the history of PAE, the blood supply of the prostate, the indications and contraindications of the technique, the operative procedure, the complications and limitations, etc. (authors)

  20. Road to Recovery from Prostate Cancer

    Full Text Available ... about robotic prostatectomies for the treatment of prostate cancer. During the program, we would like to go ... potency post- surgery. So in 2008, while prostate cancer remains a very controversial subject, it is obviously ...

  1. African American Men and Prostate Cancer

    Full Text Available ... Americans have one of the highest incidences of prostate cancer in the world, and in this country the ... is -- an epidemic. Winston Dyer: My introduction to prostate cancer started with the death of my 46-year- ...

  2. African American Men and Prostate Cancer

    Full Text Available ... have one of the highest incidences of prostate cancer in the world, and in this country the ... an epidemic. Winston Dyer: My introduction to prostate cancer started with the death of my 46-year- ...

  3. African American Men and Prostate Cancer

    Full Text Available ... Americans have one of the highest incidences of prostate cancer in the world, and in this country ... is -- an epidemic. Winston Dyer: My introduction to prostate cancer started with the death of my 46- ...

  4. Road to Recovery from Prostate Cancer

    Full Text Available ... of Urology and the Director of the Deane Prostate Health and Research Center at the Mount Sinai ... more about robotic prostatectomies for the treatment of prostate cancer. During the program, we would like to ...

  5. Road to Recovery from Prostate Cancer

    Full Text Available ... the Director of the Deane Prostate Health and Research Center at the Mount Sinai School of Medicine ... about robotic prostatectomies for the treatment of prostate cancer. During the program, we would like to go ...

  6. Road to Recovery from Prostate Cancer

    Full Text Available ... more about robotic prostatectomies for the treatment of prostate cancer. During the program, we would like to go ... and potency post- surgery. So in 2008, while prostate cancer remains a very controversial subject, it is obviously ...

  7. Road to Recovery from Prostate Cancer

    Full Text Available ... is no more incision and this is the access to the prostate, which is a little different. ... for many years. We’re just changing the access to the prostate and we’ve seen that ...

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

    Lee, JK; Phillips, JW; Smith, BA; Park, JW; Stoyanova, T; McCaffrey, EF; Baertsch, R.; Sokolov, A.; Meyerowitz, JG; Mathis, C.; Cheng, D; Stuart, JM; Shokat, KM; Gustafson, WC; Huang, J.

    2016-01-01

    MYCN amplification and overexpression are common in neuroendocrine prostate cancer (NEPC). However, the impact of aberrant N-Myc expression in prostate tumorigenesis and the cellular origin of NEPC have not been established. We define N-Myc and activated AKT1 as oncogenic components sufficient to transform human prostate epithelial cells to prostate adenocarcinoma and NEPC with phenotypic and molecular features of aggressive, late-stage human disease. We directly show that prostate adenocarci...

  9. The role of inflammatory mediators in the development of prostatic hyperplasia and prostate cancer

    Elkahwaji JE

    2012-01-01

    Johny E Elkahwaji1–31Section of Urologic Surgery, 2Section of Medical Oncology and Hematology, 3Genitourinary Oncology Research Laboratory, University of Nebraska Medical Center, Omaha, NE, USAAbstract: Benign prostatic hyperplasia and prostate cancer remain the most prevalent urologic health concerns affecting elderly men in their lifetime. Only 20% of benign prostatic hyperplasia and prostate cancer cases coexist in the same zone of the prostate and require a long time for initiat...

  10. Serum Oxidized Protein and Prostate Cancer Risk within the Prostate Cancer Prevention Trial

    Hoque, Ashraful; Ambrosone, Christine B; Till, Cathee; Goodman, Phyllis J.; Tangen, Cathy; Kristal, Alan; Lucia, Scott; Wang, Qiao; Kappil, Maya; Thompson, Ian; Hsing, Ann W.; Parnes, Howard; Lippman, Scott M.; Santella, Regina M.

    2010-01-01

    To evaluate the role of oxidative stress in prostate cancer risk, we analyzed serum levels of protein carbonyl groups in 1808 prostate cancer cases and 1805 controls, nested in the Prostate Cancer Prevention Trial, a randomized, placebo-control trial that found finasteride decreased prostate cancer risk. There were no significant differences in protein carbonyl levels in baseline samples between those later diagnosed with prostate cancer and those without at the end of study biopsy. Adjusted ...

  11. Finasteride Concentrations and Prostate Cancer Risk: Results from the Prostate Cancer Prevention Trial

    Chau, Cindy H.; Price, Douglas K.; Cathee Till; Goodman, Phyllis J.; Xiaohong Chen; Leach, Robin J; Johnson-Pais, Teresa L.; Hsing, Ann W.; Ashraful Hoque; Tangen, Catherine M.; Lisa Chu; Parnes, Howard L.; Schenk, Jeannette M.; Reichardt, Juergen K. V.; Thompson, Ian M

    2015-01-01

    Objective In the Prostate Cancer Prevention Trial (PCPT), finasteride reduced the risk of prostate cancer by 25%, even though high-grade prostate cancer was more common in the finasteride group. However, it remains to be determined whether finasteride concentrations may affect prostate cancer risk. In this study, we examined the association between serum finasteride concentrations and the risk of prostate cancer in the treatment arm of the PCPT and determined factors involved in modifying dru...

  12. Extraction of Prostatic Lumina and Automated Recognition for Prostatic Calculus Image Using PCA-SVM

    D. Joshua Liao; Yusheng Huang; Xiaofen Xing; Hua Wang; Jian Liu; Hui Xiao; Zhuocai Wang; Xiaojun Ding; Xiangmin Xu

    2011-01-01

    Identification of prostatic calculi is an important basis for determining the tissue origin. Computation-assistant diagnosis of prostatic calculi may have promising potential but is currently still less studied. We studied the extraction of prostatic lumina and automated recognition for calculus images. Extraction of lumina from prostate histology images was based on local entropy and Otsu threshold recognition using PCA-SVM and based on the texture features of prostatic calculus. The SVM cla...

  13. Genetic Determinants of Metabolism and Benign Prostate Enlargement: Associations with Prostate Volume

    Giri, Ayush; Edwards, Todd L.; Motley, Saundra S.; Byerly, Susan H.; Fowke, Jay H.

    2015-01-01

    Prostate enlargement leading to clinical benign prostatic hyperplasia (BPH) is associated with metabolic dysregulation and obesity. The genetic basis of this association is unclear. Our objective was to evaluate whether single nucleotide polymorphisms (SNPs) previously associated with metabolic disorders are also associated with prostate volume (PV). Participants included 876 men referred for prostate biopsy and found to be prostate cancer free. PV was measured by transrectal ultrasound. Samp...

  14. Impact of Benign Prostatic Hyperplasia Pharmacological Treatment on Transrectal Prostate Biopsy Adverse Effects

    Marina Zamuner; Ciro Eduardo Falcone; Arnaldo Amstalden Neto; Tomás Bernardo Costa Moretti; Luis Alberto Magna; Fernandes Denardi; Leonardo Oliveira Reis

    2014-01-01

    Background. Benign prostatic hyperplasia (BPH) pharmacological treatment may promote a decrease in prostate vascularization and bladder neck relaxation with theoretical improvement in prostate biopsy morbidity, though never explored in the literature. Methods. Among 242 consecutive unselected patients who underwent prostate biopsy, after excluding those with history of prostate biopsy/surgery or using medications not for BPH, we studied 190 patients. On the 15th day after procedure patients w...

  15. Midline Prostatic Cyst Marsupialization Using Holmium Laser

    Mehmet Kilinc; Yunus Emre Goger; Mesut Piskin; Mehmet Balasar; Abdulkadir Kandemir

    2015-01-01

    Many of the prostatic cysts are asymptomatic and only 5% are symptomatic (Hamper et al., 1990; Higashi et al., 1990). These symptoms include pelvic pain, hematospermia, infertility, voiding dysfunction, prostatitis-like syndrome, and painful ejaculation. Treatment of prostatic cysts includes TRUSG guided drainage, endoscopic transurethral resection, and in some cases even open surgery. In the literature, endoscopic interventions use marsupialization of the midline prostatic cyst with transure...

  16. Diagnosis and treatment for prostate cancer

    Zuoxing Niu; Guohua Ren; Shuping Song

    2008-01-01

    The morbility of prostate cancer has risen in China in recent years, it is important to diagnose and treat prostate cancer standardly and systemically.This review analyzed the status and advances of PSA examination, digital rectal examination, prostate biopsy in prostate cancer, and it gave a detailed description of radical prostatectomy, radiotherapy, chemotherapy, hormonal therapy, etc.The advances of targeted therapy and tumor vaccine is also discussed.

  17. AB012. Brachytherapy for localized prostate cancer

    Xu, Yong; Yang, Yong

    2016-01-01

    Background To evaluate the security and effect of brachytherapy for localized prostate cancer. Methods Forty five patients with Tl–T2 prostate cancer were treated with real-time transperineal ultrasound-guide 125I seeds prostate implantation. Results The median operation time was 90 min, the median number of I seeds used was 56. The follow up time was 12–48 months, the cases of PSA Brachytherapy for localized prostate cancer is safe and effective.

  18. Dystrophic Calcification of the Prostate after Cryotherapy

    Christopher Dru; Leon Bender

    2014-01-01

    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 cryoth...

  19. Dietary Antioxidants and Prostate Cancer: A Review

    Vance, Terrence M.; Su, Joseph; Fontham, Elizabeth T. H.; Koo, Sung I; Chun, Ock K.

    2013-01-01

    Prostate cancer is the most common non-cutaneous cancer in men in the United States. Several studies have examined the relationship between prostate cancer and antioxidants; however, the results of these studies are inconsistent. This article provides a systematic review of studies on prostate cancer and antioxidant intake from diet and supplements. Tea and coffee appear to offer protection against advanced prostate cancer. Different forms of vitamin E appear to exert different effects on pro...

  20. Solitary pulmonary metastasis from prostate sarcomatoid cancer

    Oyamada Yoshitaka; Maeshima Arafumi; Goto Taichiro; Kato Ryoichi

    2010-01-01

    Abstract Background Pulmonary metastasis from prostate cancer is considered to be a late event, and patients can be treated with chemotherapy or hormonal manipulation. However, there has been only a few reports on surgical resection for pulmonary metastasis from prostate cancer. Case Presentation We present a surgical case of solitary pulmonary metastasis from prostate cancer. A 73-year-old man underwent pelvic evisceration for prostate cancer. Histopathological examination revealed a poorly ...

  1. Epidermal growth factor in the rat prostate

    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....

  2. Prostate cancer may trigger paraneoplastic limbic encephalitis

    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, a...

  3. Improving Screening Strategies for Prostate Cancer

    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 more deta

  4. BCG induced granulomatous prostatitis ; a case report

    Granulomatous prostatitis was relatively uncommon until the introduction of intravesical BCG for the treament of bladder cancer. Since that time, there has been an increase in the number of cases of granulomatous prostatitis, but the domestic literature contains no report. We recently encountered a classic case of BCG induced granulomatous prostatitis and describe this case, including its radiologic findings. (author)=20

  5. Magnetic resonance imaging of the prostate

    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....

  6. Magnetic resonance imaging of the prostate

    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....

  7. Prevention and early detection of prostate cancer

    J. Cuzick (Jack); M.A. Thorat (Mangesh A); G. Andriole (Gerald); O.W. Brawley (Otis W); P.H. Brown (Powel H); Z. Culig (Zoran); R. Eeles (Rosalind); L.G. Ford (Leslie G); F. Hamdy (Freddie); L. Holmberg (Lars); D. Ilic (Dragan); T.J. Key (Timothy J); C.L. Vecchia (Carlo La); H. Lilja (Hans); M. Marberger (Michael); F.L. Meyskens (Frank L); L.M. Minasian (Lori M); C. Parker (C.); H.L. Parnes (Howard L); S. Perner (Sven); H. Rittenhouse (Harry); J.A. Schalken (J.); H.-P. Schmid (Hans-Peter); B.J. Schmitz-Dräger (Bernd J); F.H. Schröder (Fritz); A. Stenzl (Arnulf); B. Tombal (Bertrand); T.J. Wilt (Timothy J.); K. Wolk (Kerstin)

    2014-01-01

    textabstractProstate cancer is a common malignancy in men and the worldwide burden of this disease is rising. Lifestyle modifications such as smoking cessation, exercise, and weight control offer opportunities to reduce the risk of developing prostate cancer. Early detection of prostate cancer by pr

  8. Active surveillance for prostate cancer.

    Romero-Otero, Javier; García-Gómez, Borja; Duarte-Ojeda, José M; Rodríguez-Antolín, Alfredo; Vilaseca, Antoni; Carlsson, Sigrid V; Touijer, Karim A

    2016-03-01

    It is worth distinguishing between the two strategies of expectant management for prostate cancer. Watchful waiting entails administering non-curative androgen deprivation therapy to patients on development of symptomatic progression, whereas active surveillance entails delivering curative treatment on signs of disease progression. The objectives of the two management strategies and the patients enrolled in either are different: (i) to review the role of active surveillance as a management strategy for patients with low-risk prostate cancer; and (ii) review the benefits and pitfalls of active surveillance. We carried out a systematic review of active surveillance for prostate cancer in the literature using the National Center for Biotechnology Information's electronic database, PubMed. We carried out a search in English using the terms: active surveillance, prostate cancer, watchful waiting and conservative management. Selected studies were required to have a comprehensive description of the demographic and disease characteristics of the patients at the time of diagnosis, inclusion criteria for surveillance, and a protocol for the patients' follow up. Review articles were included, but not multiple papers from the same datasets. Active surveillance appears to reduce overtreatment in patients with low-risk prostate cancer without compromising cancer-specific survival at 10 years. Therefore, active surveillance is an option for select patients who want to avoid the side-effects inherent to the different types of immediate treatment. However, inclusion criteria for active surveillance and the most appropriate method of monitoring patients on active surveillance have not yet been standardized. PMID:26621054

  9. Prevention strategies for prostate cancer.

    Schmitz-Dräger, B J; Lümmen, G; Bismarck, E; Fischer, C

    2012-12-01

    Through the last decade consideration of the role of vitamins and minerals in primary prevention of genitourinary tumors has dramatically changed. Despite all efforts efficacy of a specific compound has not been proven, so far. In consequence, recommendations for a use of vitamins or other supplements with the intention of prostate cancer prevention should be avoided today. In contrast, there is some evidence that life style modification might be helpful: recent investigations suggest that smoking may be involved in prostate cancer carcinogenesis. In addition, there is evidence that moderate food consumption, reduction of dairy products and an Asian or Mediterranean diet might not only prevent prostate cancer but also harbors additional beneficial effects on general health. This move from single compounds to more complex diets can be considered as a change of paradigm in prostate cancer prevention and could be the starting point of future epidemiological research. Disappointing findings with regards to nutritional cancer prevention contrast with a solid evidence concerning the efficacy of chemoprevention using 5a-reductase inhibitors: Long-term use of Finasteride and Dutasteride significantly reduces prostate cancer detection. Further candidate drugs are under investigation. However, translation of these findings into urological practice remains a matter of controversial discussion. PMID:23288209

  10. Prostate cancer in the elderly.

    Konstantinos, Hatzimouratidis

    2005-01-01

    Prostate cancer is the second leading cause of cancer deaths among men. Despite earlier diagnosis due to prostate specific antigen (PSA) screening, it is still a disease of the elderly. Diagnosis is based on digital rectal examination (DRE) and PSA assessment. Refinements in PSA testing (age-specific reference ranges, free PSA, PSA density and velocity) increased specificity and limited unnecessary prostate biopsies. Diagnosis in earlier stages (T1 and T2) commonly leads to cure with current treatment modalities. These include radical prostatectomy, external beam radiotherapy and brachytherapy. Other treatment options under development include cryotherapy and high-intensity focused ultrasound. Metastatic prostate cancer is incurable and treatment is based on hormonal therapy. Cytotoxic chemotherapy has only limited role in hormone-independent prostate cancer. Radioisotopes and biphosphonates may alleviate bone pain and prevent osteoporosis and pathological fractures. Follow-up is based on PSA. Prognostic factors for recurrence include stage, Gleason score, pre- and posttreatment PSA. Quality of life issues play an important role in selecting treatment, especially in the elderly due to comorbidities that may negatively affect the overall quality of life. A holistic approach is recommended addressing all quality of life issues without focus only in cancer control. PMID:16362603

  11. Prostate cancer immunotherapy: beyond immunity to curability.

    Simons, Jonathan W

    2014-11-01

    Metastatic prostate cancer is the second leading cause of death from cancer in the United States. It is the first prevalent cancer in which overall survival in advanced disease is modestly, but objectively, improved with outpatient delivered dendritic cell-based immunotherapy. More prostate cancer patients have enrolled through Facebook and trusted-site Internet searches in clinical trials for prostate cancer vaccine-based immunotherapy than in immunotherapy trials for lung, breast, colon, pancreas, ovarian, and bladder cancer combined in the past 7 years. Exceptional responses to anti-CTLA-4 treatment have been documented in clinics, and prostate cancer neoantigen characterization and T-cell clonotyping are in their research ascendancy. The prostate is an accessory organ; it is not required for fertility, erectile function, or urinary continence. The true evolutionary advantage of having a prostate for male mammalian physiology is a topic of speculation in seminar rooms and on bar stools, but it remains unknown. Hundreds of prostate lineage-unique proteins (PLUP) exist among the >37,000 normal human prostate lineage-unique open reading frames that can be targeted for immunologic ablation of PLUP(+) prostate cancer cells by prostate-specific autoimmunity. This bioengineered graft-versus-prostate disease is a powerful strategy that can eliminate deaths from prostate cancer. Immunologic tolerance to prostate cancer can be overcome at every clinical stage of presentation. This Cancer Immunology at the Crossroads article aims to present advances in the past two decades of basic, translational, and clinical research in prostate cancer, including bioengineering B-cell and T-cell responses, and ongoing prostate cancer immunotherapy trials. PMID:25367978

  12. Intrafraction prostate motion during IMRT for prostate cancer

    Purpose: Although the interfraction motion of the prostate has been previously studied through the use of fiducial markers, CT scans, and ultrasound-based systems, intrafraction motion is not well documented. In this report, the B-mode, Acquisition, and Targeting (BAT) ultrasound system was used to measure intrafraction prostate motion during 200 intensity-modulated radiotherapy (IMRT) sessions for prostate cancer. Methods and Materials: Twenty men receiving treatment with IMRT for clinically localized prostate cancer were selected for the study. Pre- and posttreatment BAT ultrasound alignment images were collected immediately before and after IMRT on 10 treatment days for a total of 400 BAT alignment procedures. Any ultrasound shifts of the prostate borders in relation to the planning CT scan were recorded in 3 dimensions: right-left (RL), anteroposterior (AP), and superior-inferior (SI). Every ultrasound procedure was evaluated for image quality and alignment according to a 3-point grading scale. Results: All the BAT images were judged to be of acceptable quality and alignment. The dominant directions of intrafraction prostate motion were anteriorly and superiorly. The mean magnitude of shifts (±SD) was 0.01±0.4 mm, 0.2±1.3 mm, and 0.1±1.0 mm in the left, anterior, and superior directions, respectively. The maximal range of motion occurred in the AP dimension, from 6.8 mm anteriorly to 4.6 mm posteriorly. The percentage of treatments during which prostate motion was judged to be ≤5 mm was 100%, 99%, and 99.5% in the RL, AP, and SI directions, respectively. Three of the measurements were >5 mm. The extent of intrafraction motion was much smaller than that of interfraction motion. Linear regression analysis showed very little correlation between the two types of motion (r=0.014, 0.029, and 0.191, respectively) in the RL, AP, and SI directions. Conclusion: Using an ultrasound-based system, intrafraction prostate motion occurred predominantly in the anterior

  13. Prostate cancer and metastasis initiating stem cells

    Kathleen Kelly; Juan Juan Yin

    2008-01-01

    Androgen refractory prostate cancer metastasis is a major clinical challenge.Mechanism-based approaches to treating prostate cancer metastasis require an understanding of the developmental origin of the metastasis-initiating cell.Properties of prostate cancer metastases such as plasticity with respect to differentiated phenotype and androgen independence are consistent with the transformation of a prostate epithelial progenitor or stem cell leading to metastasis.This review focuses upon current evidence and concepts addressing the identification and properties of normal prostate stem or progenitor cells and their transformed counterparts.

  14. Screening spectroscopy of prostate cancer

    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.

  15. ESUR prostate MR guidelines 2012

    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 for the optimal technique and three protocols for ''detection'', ''staging'' and ''node and bone'' are presented. The use of endorectal coil vs. pelvic phased array coil and 1.5 vs. 3 T is discussed. Clinical indications and a PI-RADS classification for structured reporting are presented. (orig.)

  16. [Prostate cancer and chemotherapy].

    Gravis, Gwenaelle; Salem, Naji; Bladou, Franck; Viens, Patrice

    2007-07-01

    Androgen deprivation in patients with metastatic prostate cancer produces palliation of symptoms, PSA decrease and tumoral regression in most patients. After a brief period of disease regression lasting 18 to 24 months nearly all pts will progress to androgen independence disease (HRPC) with progressive clinical deterioration and ultimately death. Chemotherapy with mitoxantrone has been shown to palliate symptoms but did not extend survival. Two large randomized trials showed a survival benefit for pts with HRPC treated with docetaxel with a reduction risk of death by 21-24%, and significant improvement in palliation of symptoms and quality of life. New agents targeting angiogenesis, apoptosis, signal transduction pathway, used alone or in combination with docetaxel currently are under trial in an attempt to provide much needed improvements in outcome. Questions remains in suspend when and who need to be treated, earlier, in high risk as in adjuvant setting? Current data have demonstrated that neoadjuvant or adjuvant chemotherapy is relatively safe and feasible. Further investigation through prospective randomize trials is critical to define the precise role of this modality in high risk populations. PMID:17845990

  17. Giant Benign Prostatic Hyperplasia in a Pakistani Patient *

    Zafaruddin Khan; Muzamil Tahir; H. Shahzad Ashraf; FazaluRehman Khan Niazi; Munazza Khan; Sadaf Mustafa; Naseruddin Höti

    2014-01-01

    “Giant hyperplasia” of the prostate is a rare pathology of the prostate gland. We report one such case, in which a successful retropubic prostatectomy was performed on an elderly male patient in Pakistan. The weight of the resected prostate was 700 g, which is the eighth largest prostate with benign prostatic hyperplasia reported.

  18. Histopathologic characteristics of the prostatic intraepithelial neoplasia

    The prostate disease is a health problem nowadays due to its high morbidity and mortality in adults older than 50 years. Based on this, a descriptive and cross sectional study was carried out on the histopathologic findings of the prostatic intraepithelial neoplasia in the useful prostate biopsies examined in the Pathology Department of 'Dr. Ambrosio Grillo Portuondo' Clinical Surgical Teaching Hospital in Santiago de Cuba during the biennium 2008-2009. Among the main results there were: the confirmation of prostate fibroadenomatous hyperplasia, prostatic lesions, carcinomas and other alterations in that male gland, all through biopsy. The obtained data confirmed that the diagnosis through samples from the prostatic intraepithelial neoplasia tissue, constitutes one of the ways by which pathologists can contribute to the opportune detection of the prostatic carcinoma. (author)

  19. Detection of DNA viruses in prostate cancer

    Smelov, Vitaly; Bzhalava, Davit; Arroyo Mühr, Laila Sara; Eklund, Carina; Komyakov, Boris; Gorelov, Andrey; Dillner, Joakim; Hultin, Emilie

    2016-01-01

    We tested prostatic secretions from men with and without prostate cancer (13 cases and 13 matched controls) or prostatitis (18 cases and 18 matched controls) with metagenomic sequencing. A large number (>200) of viral reads was only detected among four prostate cancer cases (1 patient each positive for Merkel cell polyomavirus, JC polyomavirus and Human Papillomavirus types 89 or 40, respectively). Lower numbers of reads from a large variety of viruses were detected in all patient groups. Our knowledge of the biology of the prostate may be furthered by the fact that DNA viruses are commonly shed from the prostate and can be readily detected by metagenomic sequencing of expressed prostate secretions. PMID:27121729

  20. Inflammatory Genetic Markers of Prostate Cancer Risk

    Prostate cancer is the most common cancer in Western society males, with incidence rates predicted to rise with global aging. Etiology of prostate cancer is however poorly understood, while current diagnostic tools can be invasive (digital rectal exam or biopsy) and/or lack specificity for the disease (prostate-specific antigen (PSA) testing). Substantial histological, epidemiological and molecular genetic evidence indicates that inflammation is important in prostate cancer pathogenesis. In this review, we summarize the current status of inflammatory genetic markers influencing susceptibility to prostate cancer. The focus will be on inflammatory cytokines regulating T-helper cell and chemokine homeostasis, together with the Toll-like receptors as key players in the host innate immune system. Although association studies indicating a genetic basis for prostate cancer are presently limited mainly due to lack of replication, larger and more ethnically and clinically defined study populations may help elucidate the true contribution of inflammatory gene variants to prostate cancer risk

  1. INaP selective inhibition reverts precocious inter- and motorneurons hyperexcitability in the Sod1-G93R zebrafish ALS model

    Benedetti, Lorena; Ghilardi, Anna; Rottoli, Elsa; De Maglie, Marcella; Prosperi, Laura; Perego, Carla; Baruscotti, Mirko; Bucchi, Annalisa; Del Giacco, Luca; Francolini, Maura

    2016-01-01

    The pathogenic role of SOD1 mutations in amyotrophic lateral sclerosis (ALS) was investigated using a zebrafish disease model stably expressing the ALS-linked G93R mutation. In addition to the main pathological features of ALS shown by adult fish, we found remarkably precocious alterations in the development of motor nerve circuitry and embryo behavior, and suggest that these alterations are prompted by interneuron and motor neuron hyperexcitability triggered by anomalies in the persistent pacemaker sodium current INaP. The riluzole-induced modulation of INaP reduced spinal neuron excitability, reverted the behavioral phenotypes and improved the deficits in motor nerve circuitry development, thus shedding new light on the use of riluzole in the management of ALS. Our findings provide a valid phenotype-based tool for unbiased in vivo drug screening that can be used to develop new therapies. PMID:27079797

  2. An unusual case of retrovesical ectopic prostate tissue accompanied by primary prostate cancer.

    Tan, Fu-Qing; Xu, Xin; Shen, Bo-Hua; Qin, Jie; Sun, Ke; You, Qihan; Shang, De-Sheng; Zheng, Xiang-Yi

    2012-01-01

    We report an unusual case of retrovesical ectopic prostate tissue in a 73-year-old man with primary prostate cancer. The man's prostate-specific antigen was 24.66 ng/ml.Transabdominal ultrasonography, pelvic computed tomography,and pelvic magnetic resonance imaging demonstrated a heterogeneous 8.5 × 8.0 × 7.0 cm mass in contact with the posterior wall of the urinary bladder. The patient underwent a retropubic radical prostatectomy and resection of tumor. Pathological examination of prostate revealed a prostatic adenocarcinoma, Gleason score of 4 + 5 = 9, and the retrovesical tumor was confirmed to be a benign prostate tissue. PMID:22966979

  3. Proton MR spectroscopy of the prostate

    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.

  4. Proton MR spectroscopy of the prostate

    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

  5. What I Need to Know about Prostate Problems

    ... Cancer Information Service Alternate Language URL Españ​ol What I need to know about Prostate Problems Page ... Diet, and Nutrition Points to Remember Clinical Trials What are common prostate problems? Common prostate problems include ...

  6. Acute Bacterial Prostatitis: Diagnosis and Management.

    Coker, Timothy J; Dierfeldt, Daniel M

    2016-01-15

    Acute bacterial prostatitis is an acute infection of the prostate gland that causes pelvic pain and urinary tract symptoms, such as dysuria, urinary frequency, and urinary retention, and may lead to systemic symptoms, such as fevers, chills, nausea, emesis, and malaise. Although the true incidence is unknown, acute bacterial prostatitis is estimated to comprise approximately 10% of all cases of prostatitis. Most acute bacterial prostatitis infections are community acquired, but some occur after transurethral manipulation procedures, such as urethral catheterization and cystoscopy, or after transrectal prostate biopsy. The physical examination should include abdominal, genital, and digital rectal examination to assess for a tender, enlarged, or boggy prostate. Diagnosis is predominantly made based on history and physical examination, but may be aided by urinalysis. Urine cultures should be obtained in all patients who are suspected of having acute bacterial prostatitis to determine the responsible bacteria and its antibiotic sensitivity pattern. Additional laboratory studies can be obtained based on risk factors and severity of illness. Radiography is typically unnecessary. Most patients can be treated as outpatients with oral antibiotics and supportive measures. Hospitalization and broad-spectrum intravenous antibiotics should be considered in patients who are systemically ill, unable to voluntarily urinate, unable to tolerate oral intake, or have risk factors for antibiotic resistance. Typical antibiotic regimens include ceftriaxone and doxycycline, ciprofloxacin, and piperacillin/tazobactam. The risk of nosocomial bacterial prostatitis can be reduced by using antibiotics, such as ciprofloxacin, before transrectal prostate biopsy. PMID:26926407

  7. Prostate Cancer Risk Prediction Models

    Developing statistical models that estimate the probability of developing prostate cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  8. [Chronic prostatitis and Bechterew's disease].

    Kohlicek, J; Svec, V

    1977-11-01

    A group of patients between 35 and 65 years old with chronic prostatitis were examined for the presence of Becherew's disease. In this connection the New York and Roman criterions for morbus Bechterew were applied. There were found one ankyosing spondylarthritis, one ankylosis of the sacroiliac joint, and 11 times a tentative sacroileitis were stated. Altogether the proved and tentative findings were only 3.68 per cent of all examinations. In our countries the morbus Bechterew is found in 0,21 per cent of the normal population. So the protion of the Bechterew's disease in patients with chronic prostatitis is indeed a little higher than average, but not so frequent as often pretended in recent times. After a second series 58 patients being treated because of Bechterew's disease of different stages and different terms were examined for the possibility of a simultaneously elapsing chronic prostatitis. A chronic prostatitis was found in 38 per cent of these patients which correspondents to the incidence published in literature for the medium-age manhood. Nobody of the test persons had complaints on the part of the urologenital tract. PMID:602457

  9. Erectile function after prostate brachytherapy

    Purpose: To evaluate erectile function after permanent prostate brachytherapy using a validated patient-administered questionnaire and to determine the effect of multiple clinical, treatment, and dosimetric parameters on penile erectile function. Methods and materials: A total of 226 patients with preimplant erectile function determined by the International Index of Erectile Function (IIEF) questionnaire underwent permanent prostate brachytherapy in two prospective randomized trials between February 2001 and January 2003 for clinical Stage T1c-T2c (2002 American Joint Committee on Cancer) prostate cancer. Of the 226 patients, 132 were potent before treatment and, of those, 128 (97%) completed and returned the IIEF questionnaire after brachytherapy. The median follow-up was 29.1 months. Potency was defined as an IIEF score of ≥13. The clinical, treatment, and dosimetric parameters evaluated included patient age; preimplant IIEF score; clinical T stage; pretreatment prostate-specific antigen level; Gleason score; elapsed time after implantation; preimplant nocturnal erections; body mass index; presence of hypertension or diabetes mellitus; tobacco consumption; the volume of the prostate gland receiving 100%, 150%, and 200% of the prescribed dose (V100/150/200); the dose delivered to 90% of the prostate gland (D90); androgen deprivation therapy; supplemental external beam radiotherapy (EBRT); isotope; prostate volume; planning volume; and radiation dose to the proximal penis. Results: The 3-year actuarial rate of potency preservation was 50.5%. For patients who maintained adequate posttreatment erectile function, the preimplant IIEF score was 29, and in patients with brachytherapy-related ED, the preimplant IIEF score was 25. The median time to the onset of ED was 5.4 months. After brachytherapy, the median IIEF score was 20 in potent patients and 3 in impotent patients. On univariate analysis, the preimplant IIEF score, patient age, presence of nocturnal erections

  10. Undiagnosed prostatic malignancy at the time of radical cystoprostatectomy after prior prostatic radiation therapy

    Pranav Sharma

    2016-01-01

    Conclusions: Despite prior XRT for PCa, less than one-third of patients had no prostatic disease at the time of RC. Routine prostatic sampling should be considered in these patients especially if considering the orthotopic diversion.

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

    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.

  12. Gene therapy for prostate cancer.

    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

  13. Clinical survey of prostate cancer

    Treatment trends and outcomes for prostate cancer in our hospital were reported. A total of 482 patients with prostate cancer treated in our hospital between January, 1990 and December, 2004. The age distribution was from 51 to 99 years-old, with the mean age of 72.9 years-old at onset. The number of prostate cancer patients, especially asymptomatic patients with prostatic specific antigen (PSA) elevation, have increased recently. As for the clinical stage, 92 cases (19.1%), 238 cases (49.4%), 48 cases (10.0%) and 104 cases (21.6%) were stage A, B, C and D, respectively. 425 cases (88.2%) received some form of endocrine therapy. Retropubic prostatectomy or external beam radiation therapy was performed in 77 and 57 cases, respectively all cases. The cause-specific 5-year survival rate of the 482 cases was 79.7%, comprising 100% for stage A1, 96.8% for stage A2, 89.4% for stage B, 79.9% for stage C and 42.9% for stage D. The cause-specific 5-year survival was significantly better in the latter patients (1997-2004) than the former patients (1990-1996) in stage C (p=0.0226), D (p=0.0448). In stage C patients, the retropubic prostatectomy (with endocrine therapy) group, increased in the latter period and showed longer cause-specific 5-year survival than the endocrine therapy group (p=0.0027). In stage D2 patients, chemo-endocrine therapy with etoposide (VP-16), adriamycin (ADM) and cisplatin (CDDP) refractory and cause-specific 5-year survival was longer than endocrine therapy alone (p=0.0467, P=0.0381). Our results suggest that retropubic prostatectomy with endocrine therapy and chemo-endocrine therapy are useful for stage C and D prostate cancer patients, respectively. (author)

  14. Gene therapy for prostate cancer.

    Tangney, Mark; Ahmad, Sarfraz; Collins, Sara A; O'Sullivan, Gerald C

    2010-05-01

    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

  15. EVALUATION OF FREE-TO-TOTAL PROSTATE SPECIFIC ANTIGEN RATIO IN THE DIAGNOSIS OF PROSTATE CANCER

    2000-01-01

    @@ It's reported that free to total prostate specific antigen ration (f/tPSA) can provide more benefit than the single use of prostate specific antigen (PSA) in the diagnosis of prostate cancer (PCa). We measured serum PSA and fPSA levels in 62 cases of benign prostatic hyperplasia (BPH) and 40 cases of PCa using radioimmunoassay, with patients' age range 59y~ 89y.

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

    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....

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

    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 ...

  18. Multiparametric magnetic resonance imaging predicts the presence of prostate cancer in patients with negative prostate biopsy

    Lista, F; Castillo, Ernesto; Gimbernat, H.; Rodríguez-Barbero, José M.; Panizo, J.; Angulo Cuesta, Javier

    2015-01-01

    The objective of this study is to assess the ability of multiparametric prostate magnetic resonance imaging (mpMRI) to detect prostate cancer in patients with prior negative transrectal prostate biopsy (TPB). mpMRI (TSE-T2-w, DWI and DCE sequences) was performed on 1.5 T (Magnetom Avanto; Siemens Healthcare Solutions) in 150 patients suspicious of prostate cancer and with negative TPB. European Society of Urogenital Radiology (ESUR) criteria were used. PSA measurement (total and free), digita...

  19. TRICHOMONOSIS AND SUBSEQUENT RISK OF PROSTATE CANCER IN THE PROSTATE CANCER PREVENTION TRIAL

    Sutcliffe, Siobhan; Alderete, John F.; Till, Cathee; Goodman, Phyllis J.; Hsing, Ann W.; Zenilman, Jonathan M; De Marzo, Angelo M.; Platz, Elizabeth A.

    2009-01-01

    We previously observed a positive association between a history of trichomonosis, a sexually transmitted infection caused by the protozoan, Trichomonas vaginalis, and prostate cancer risk in the Health Professionals Follow-up Study. To determine the reproducibility of this finding, we conducted a second, prospective investigation of trichomonosis and prostate cancer in the Prostate Cancer Prevention Trial. Participants were men ≥55 years of age with no evidence of prostate cancer at enrollmen...

  20. Prostate-specific antigen in the early detection of prostate cancer

    Thompson, Ian M; Ankerst, Donna P.

    2007-01-01

    Throughout Canada, the United States and much of Europe, prostate-specific antigen (PSA) screening for prostate cancer has proliferated over the past 2 decades, leading to dramatic increases in detection rates of prostate cancer. Although it has unquestionably led to increased detection of cancer and a migration to lower-stage and -volume tumours, it is still unknown whether PSA screening significantly reduces mortality from prostate cancer. Often thought to be dichotomous (i.e., either norma...

  1. Diet, Supplement Use, and Prostate Cancer Risk: Results From the Prostate Cancer Prevention Trial

    Kristal, Alan R.; Arnold, Kathryn B.; Neuhouser, Marian L; Goodman, Phyllis; Platz, Elizabeth A.; Albanes, Demetrius; Thompson, Ian M

    2010-01-01

    The authors examined nutritional risk factors for prostate cancer among 9,559 participants in the Prostate Cancer Prevention Trial (United States and Canada, 1994–2003). The presence or absence of cancer was determined by prostate biopsy, which was recommended during the trial because of an elevated prostate-specific antigen level or an abnormal digital rectal examination and was offered to all men at the trial's end. Nutrient intake was assessed using a food frequency questionnaire and a str...

  2. Serum Phospholipid Fatty Acids and Prostate Cancer Risk: Results From the Prostate Cancer Prevention Trial

    Brasky, Theodore M.; Till, Cathee; White, Emily; Neuhouser, Marian L; Song, Xiaoling; Goodman, Phyllis; Thompson, Ian M; King, Irena B.; Albanes, Demetrius; Kristal, Alan R.

    2011-01-01

    Inflammation may be involved in prostate cancer development and progression. This study examined the associations between inflammation-related phospholipid fatty acids and the 7-year-period prevalence of prostate cancer in a nested case-control analysis of participants, aged 55–84 years, in the Prostate Cancer Prevention Trial during 1994–2003. Cases (n = 1,658) were frequency matched to controls (n = 1,803) on age, treatment, and prostate cancer family history. Phospholipid fatty acids were ...

  3. Risk Factors for Acute Prostatitis after Transrectal Biopsy of the Prostate

    Kim, Sang Jin; Kim, Sun Il; Ahn, Hyun Soo; Choi, Jong Bo; Kim, Young Soo; Kim, Se Joong

    2010-01-01

    Purpose To investigate the incidence, clinical features, pathogenic bacteria, and risk factors associated with acute prostatitis after transrectal prostate biopsy. Materials and Methods We retrospectively reviewed the medical records of 923 transrectal ultrasound-guided needle biopsies of the prostate in 878 patients performed at our institution from June 2004 to May 2009. The indications for biopsy were generally serum prostate-specific antigen (PSA) elevation, abnormal findings on a digital...

  4. Investigation of the algT operon sequence in mucoid and non-mucoid Pseudomonas aeruginosa isolates from 115 Scandinavian patients with cystic fibrosis and in 88 in vitro non-mucoid revertants

    Ciofu, Oana; Lee, Baoleri; Johannesson, Marie;

    2008-01-01

    are revertants. None of the non-mucoid isolates from intermittently colonized CF patients harboured mucA mutations. Although algT has been considered an important gene for secondary-site mutations responsible for reversion to non-mucoidy, only 30 % of the mucA-mutated non-mucoid CF isolates had mutations in alg...

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

    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 result

  6. Elevated Prostate Health Index (phi) and Biopsy Reclassification During Active Surveillance of Prostate Cancer

    Darian Andreas; Tosoian, Jeffrey J.; Patricia Landis; Sacha Wolf; Stephanie Glavaris; Lotan, Tamara L.; Schaeffer, Edward M.; Sokoll, Lori J.; Ross, Ashley E.

    2016-01-01

    The Prostate Health Index (phi) has been FDA approved for decision-making regarding prostate biopsy. Phi has additionally been shown to positively correlate with tumor volume, extraprostatic disease and higher Gleason grade tumors. Here we describe a case in which an elevated phi encouraged biopsy of a gentleman undergoing active surveillance leading to reclassification of his disease as high risk prostate cancer.

  7. Dystrophic Calcification of the Prostate after Cryotherapy

    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.

  8. The impact of obesity towards prostate diseases.

    Parikesit, Dyandra; Mochtar, Chaidir Arief; Umbas, Rainy; Hamid, Agus Rizal Ardy Hariandy

    2016-03-01

    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. PMID:27014656

  9. [Novel treatment for prostate cancer targeting prostaglandins].

    Terada, Naoki; Inoue, Takahiro; Kamba, Tomomi; Ogawa, Osamu

    2014-12-01

    PGE2 is highly expressed in the prostate, associating with prostate cancer progression. Targeting downstream signaling pathways of PGE2 may represent an attractive new strategy for the treatment of prostate cancer. We have established a novel prostate cancer xenograft model, KUCaP-2. The expression of EP4, one of PGE2 receptors, was significantly up-regulated during the development of castration resistance. A specific EP4 antagonist, ONO-AE3-208, decelerated castration-resistant growth of KUCaP-2 tumors in vivo. Moreover, ONO-AE3-208 could in vitro inhibit the cell invasion and in vivo suppress the bone metastasis of prostate cancer cells. These results indicated that EP4 is a novel target for the treatment of metastatic castration resistant prostate cancer. PMID:25518348

  10. Development of New Treatments for Prostate Cancer

    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

  11. The genomic landscape of prostate cancer

    Sylvan eBaca

    2012-05-01

    Full Text Available Prostate cancer is a common malignancy in men, with a markedly variable clinical course. Somatic alterations in DNA drive the growth of prostate cancers and may underlie the behavior of aggressive versus indolent tumors. The accelerating application of genomic technologies over the last two decades has identified mutations that drive prostate cancer formation, progression, and therapeutic resistance. Here, we discuss exemplary somatic mutations in prostate cancer, and highlight mutated cellular pathways with biological and possible therapeutic importance. Examples include mutated genes involved in androgen signaling, cell cycle regulation, signal transduction and development. Some genetic alterations may also predict the clinical course of disease or response to therapy, although the molecular heterogeneity of prostate tumors poses challenges to genomic biomarker identification. The widespread application of massively parallel sequencing technology to the analysis of prostate cancer genomes should continue to advance both discovery-oriented and diagnostic avenues.

  12. Cancer of the prostate - role of PSA

    Since 1979 when prostate specific antigen (PSA), found in the cytoplasm of benign and malignant prostatic cells, was first purified, it has attained world wide popularity in prostate cancer detection. It is also a sensitive test for skeletal meta states from carcinoma of the prostate. Prostate cancer has become the number one cancer in men and constitutes 11% of all cancers. Approximately 50% of men over 50 years have symptoms referable to the lower urinary tract. 50% or more of patients at Ibadan present an advanced stage of the disease and are therefore not curable. Thus, lacking the skill to manage advanced manifestations, early detection and screening programs are the best means to reduce mortality due to prostate cancer

  13. Aztreonam concentrations in human prostatic tissue.

    Madsen, P O; Dhruv, R; Friedhoff, L T

    1984-01-01

    The concentrations of aztreonam in human prostatic tissue specimens obtained by transurethral resection were measured in nine patients after the intramuscular administration of a single 1-g dose. The average concentration of aztreonam was 7.8 microgram/g of prostate between 50 and 180 min after dosage. The average ratio of the drug concentration in prostate to that in serum was 0.25. The concentrations of aztreonam achieved were significantly higher than the MICs for most members of the famil...

  14. Prostate Cancer and Bone: The Elective Affinities

    Nadia Rucci; Adriano Angelucci

    2014-01-01

    The onset of metastases dramatically changes the prognosis of prostate cancer patients, determining increased morbidity and a drastic fall in survival expectancy. Bone is a common site of metastases in few types of cancer, and it represents the most frequent metastatic site in prostate cancer. Of note, the prevalence of tumor relapse to the bone appears to be increasing over the years, likely due to a longer overall survival of prostate cancer patients. Bone tropism represents an intriguing c...

  15. CRITICAL REVIEW OF PROSTATE CANCER PREDICTIVE TOOLS

    Shahrokh F. Shariat; Michael W Kattan; Vickers, Andrew J; Karakiewicz, Pierre I; Scardino, Peter T.

    2009-01-01

    Prostate cancer is a very complex disease, and the decision-making process requires the clinician to balance clinical benefits, life expectancy, comorbidities, and potential treatment related side effects. Accurate prediction of clinical outcomes may help in the difficult process of making decisions related to prostate cancer. In this review, we discuss attributes of predictive tools and systematically review those available for prostate cancer. Types of tools include probability formulas, lo...

  16. New serum biomarkers for prostate cancer diagnosis

    Chadha, Kailash C.; Austin Miller; Nair, Bindukumar B.; Schwartz, Stanley A.; Trump, Donald L.; Willie Underwood

    2014-01-01

    Background: Prostate-specific antigen (PSA) is currently used as a biomarker for diagnosis and management of prostate cancer (CaP). However, PSA typically lacks the sensitivity and specificity desired of a diagnostic marker. Objective: The goal of this study was to identify an additional biomarker or a panel of biomarkers that is more sensitive and specific than PSA in differentiating benign versus malignant prostate disease and/or localized CaP versus metastatic CaP. Methods: Concurrent meas...

  17. Immunotherapy and Immune Evasion in Prostate Cancer

    Archana Thakur; Ulka Vaishampayan; Lum, Lawrence G.

    2013-01-01

    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 o...

  18. Molecular Profiling of Prostate Cancer Patients

    Nna, Emmanuel Okechukwu

    2009-01-01

    In the UK, more than 30 000 men are diagnosed annually with prostate cancer (PCa) and about 10 000 men die from it each year. Although several molecular markers have been associated with prostate cancer development and/ or progression, only few of them are used in diagnostic pathology. The current standard tests include serum PSA test, digital rectal examination and histology of prostate biopsy. Recently the PCA-3 molecular test was approved in the European Union, and it is now...

  19. Bipolar Saline TURP for Large Prostate Glands

    Finley, David S.; Shawn Beck; Szabo, Richard J.

    2007-01-01

    The objective of this study was to evaluate the feasibility of bipolar transurethral resection of the prostate ( TURP) in patients with very large prostate glands and significant comorbidities. Four patients with prostate glands > 160 cc on preoperative volume measurement and ASA class three or higher underwent bipolar TURP with the Gyrus PlasmaKinetic system. Preoperative, operative, and postoperative parameters were studied. The results showed an average ASA class 3.25 (range: 3-4). The ave...

  20. Vitamin D, Sunlight and Prostate Cancer Risk

    Krishna Vanaja Donkena; Young, Charles Y. F.

    2011-01-01

    Prostate cancer is the second common cancer in men worldwide. The prevention of prostate cancer remains a challenge to researchers and clinicians. Here, we review the relationship of vitamin D and sunlight to prostate cancer risk. Ultraviolet radiation of the sunlight is the main stimulator for vitamin D production in humans. Vitamin D's antiprostate cancer activities may be involved in the actions through the pathways mediated by vitamin D metabolites, vitamin D metabolizing enzymes, vitamin...

  1. Progress in Gene Therapy for Prostate Cancer

    KamranAliAhmed; BrianJamesDavis; TorrenceMWilson; GregoryAWiseman; MarkJFederspiel; JohnCMorris

    2012-01-01

    Gene therapy has held promise to correct various disease processes. Prostate cancer represents the second leading cause of cancer death in American men. A number of clinical trials involving gene therapy for the treatment of prostate cancer have been reported. The ability to efficiently transduce tumors with effective levels of therapeutic genes has been identified as a fundamental barrier to effective cancer gene therapy. The approach utilizing gene therapy in prostate cancer patients at our...

  2. Obesity, body composition, and prostate cancer

    Fowke Jay H; Motley Saundra S; Concepcion Raoul S; Penson David F; Barocas Daniel A

    2012-01-01

    Abstract Background Established risk factors for prostate cancer have not translated to effective prevention or adjuvant care strategies. Several epidemiologic studies suggest greater body adiposity may be a modifiable risk factor for high-grade (Gleason 7, Gleason 8-10) prostate cancer and prostate cancer mortality. However, BMI only approximates body adiposity, and may be confounded by centralized fat deposition or lean body mass in older men. Our objective was to use bioelectric impedance ...

  3. Overexpression of vimentin in canine prostatic carcinoma

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

    2011-01-01

    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....

  4. Multidisciplinary Functional MR Imaging for Prostate Cancer

    Kim, Jeong Kon; Jang, Yun-Jin; Cho, Gyunggoo

    2009-01-01

    Various functional magnetic resonance (MR) imaging techniques are used for evaluating prostate cancer including diffusion-weighted imaging, dynamic contrast-enhanced MR imaging, and MR spectroscopy. These techniques provide unique information that is helpful to differentiate prostate cancer from non-cancerous tissue and have been proven to improve the diagnostic performance of MRI not only for cancer detection, but also for staging, post-treatment monitoring, and guiding prostate biopsies. Ho...

  5. [Optimization of prostate biopsy strategy in diagnosis of prostate cancer].

    Kimura, Go

    2016-01-01

    The prostate gland is the sole organ that uses not targeted but systematic biopsy in the pathological diagnosis of prostate cancer due to its anatomical location and lack of adequate imaging modality to depict cancer nodules clearly. The U.S. Preventive Services Task Force published that the harms of PSA based screening outweigh the benefits, yielding a grade D recommendation against screening. In this current situation, what we need is to optimize a biopsy template that maximizes the detection rate of clinically significant cancer and provides adequate pathological information for a treatment plan while minimizing the detection of indolent cancers and has good cost-effectiveness and safety. In this manuscript, optimal systematic biopsy templates and possible role of MRI-guided biopsy are reviewed. PMID:26793884

  6. Immunotherapy and Immune Evasion in Prostate Cancer

    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.

  7. Management of patients with advanced prostate cancer

    Gillessen, S; Omlin, A; Attard, G;

    2015-01-01

    The first St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) Expert Panel identified and reviewed the available evidence for the ten most important areas of controversy in advanced prostate cancer (APC) management. The successful registration of several drugs for castration......-resistant prostate cancer and the recent studies of chemo-hormonal therapy in men with castration-naïve prostate cancer have led to considerable uncertainty as to the best treatment choices, sequence of treatment options and appropriate patient selection. Management recommendations based on expert opinion, and not...

  8. Role of androgen receptor in prostate cancer

    HiroyoshiSuzuki; HaruoIto

    1999-01-01

    The growth of prostate cancer is sensitive to androgen, and hormonal therapy has been used for treatment of ad-vanced cancer. About 80 % of prostate cancers initially respond to hormonal therapy, howcrver, more than half of the re-sponders gradtmlly become resistant to this therapy. Changes in tumors from an androgen-responsive to an androgen-unre-sponsive state have been widely discussed. Since androgen action is mediated by androgen receptor (AR), abnonnalitiesof AR is believed to play an important role of the loss of androgen responsiveness in prostate cancer. "Ilais article focusedon the role of AR in the progression of prostate cancer.

  9. Immunotherapy and Immune Evasion in Prostate Cancer

    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

  10. Emphysematous prostatic abscess with rectoprostatic fistula

    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.

  11. Diffusion-weighted MRI of the prostate

    Diffusion-weighted magnetic resonance imaging (DWI) can complement MRI of the prostate in the detection and localization of prostate cancer, particularly after previous negative biopsy. A total of 13 original reports and 2 reviews published in 2010 demonstrate that prostate cancer can be detected by DWI due to its increased cell density and decreased diffusiveness, either qualitatively in DWI images or quantitatively by means of the apparent diffusion coefficient (ADC). In the prostate, the ADC is influenced by the strength of diffusion weighting, localization (peripheral or transitional zone), presence of prostatitis or hemorrhage and density and differentiation of prostate cancer cells. Mean differences between healthy tissue of the peripheral zone and prostate cancer appear to be smaller for ADC than for the (choline + creatine)/citrate ratio in MR spectroscopy. Test quality parameters vary greatly between different studies but appear to be slightly better for combined MRI and DWI than for MRI of the prostate alone. Clinical validation of DWI of the prostate requires both increased technical conformity and increased numbers of patients in clinical studies. (orig.)

  12. Prostate-Specific Natural Health Products (Dietary Supplements) Radiosensitize Normal Prostate Cells

    Purpose: Prostate-specific health products (dietary supplements) are taken by cancer patients to alleviate the symptoms linked with poor prostate health. However, the effect of these agents on evidence-based radiotherapy practice is poorly understood. The present study aimed to determine whether dietary supplements radiosensitized normal prostate or prostate cancer cell lines. Methods and Materials: Three well-known prostate-specific dietary supplements were purchased from commercial sources available to patients (Trinovin, Provelex, and Prostate Rx). The cells used in the study included normal prostate lines (RWPE-1 and PWR-1E), prostate tumor lines (PC3, DU145, and LNCaP), and a normal nonprostate line (HaCaT). Supplement toxicity was assessed using cell proliferation assays [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] and cellular radiosensitivity using conventional clonogenic assays (0.5-4Gy). Cell cycle kinetics were assessed using the bromodeoxyuridine/propidium iodide pulse-labeling technique, apoptosis by scoring caspase-3 activation, and DNA repair by assessing γH2AX. Results: The cell growth and radiosensitivity of the malignant PC3, DU145, and LNcaP cells were not affected by any of the dietary prostate supplements (Provelex [2μg/mL], Trinovin [10μg/mL], and Prostate Rx [50 μg/mL]). However, both Trinovin (10μg/mL) and Prostate Rx (6μg/mL) inhibited the growth rate of the normal prostate cell lines. Prostate Rx increased cellular radiosensitivity of RWPE-1 cells through the inhibition of DNA repair. Conclusion: The use of prostate-specific dietary supplements should be discouraged during radiotherapy owing to the preferential radiosensitization of normal prostate cells.

  13. Association between Biomarkers of Obesity and Risk of High-Grade Prostatic Intraepithelial Neoplasia and Prostate Cancer - Evidence of Effect Modification by Prostate Size

    Fowke, Jay H.; Motley, Saundra; Dai, Qi; Concepcion, Raoul; Barocas, Daniel A.

    2012-01-01

    Prostate enlargement is common with aging and obesity. We investigated the association between obesity and prostate cancer controlling for differential detection related to prostate enlargement. In an analysis of 500 men, we found body mass index, waist-hip ratio, and blood leptin levels were significantly associated with high-grade PC, but only among men without prostate enlargement. Leptin was also significantly associated with high-grade prostatic intraepithelial neoplasia (HGPIN) in the a...

  14. Optimization of Radiation Therapy Techniques for Prostate Cancer With Prostate-Rectum Spacers: A Systematic Review

    Dose-escalated radiation therapy for localized prostate cancer improves disease control but is also associated with worse rectal toxicity. A spacer placed between the prostate and rectum can be used to displace the anterior rectal wall outside of the high-dose radiation regions and potentially minimize radiation-induced rectal toxicity. This systematic review focuses on the published data regarding the different types of commercially available prostate-rectum spacers. Dosimetric results and preliminary clinical data using prostate-rectum spacers in patients with localized prostate cancer treated by curative radiation therapy are compared and discussed

  15. Management of Benign Prostatic Hyperplasia.

    Kim, Eric H; Larson, Jeffrey A; Andriole, Gerald L

    2016-01-01

    Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms (LUTS) commonly affect older men. Age-related changes associated with metabolic disturbances, changes in hormone balance, and chronic inflammation may cause BPH development. The diagnosis of BPH hinges on a thorough medical history and focused physical examination, with attention to other conditions that may be causing LUTS. Digital rectal examination and urinalysis should be performed. Other testing may be considered depending on presentation of symptoms, including prostate-specific antigen, serum creatinine, urine cytology, imaging, cystourethroscopy, post-void residual, and pressure-flow studies. Many medical and surgical treatment options exist. Surgery should be reserved for patients who either have failed medical management or have complications from BPH, such as recurrent urinary tract infections, refractory urinary retention, bladder stones, or renal insufficiency as a result of obstructive uropathy. PMID:26331999

  16. [Medical treatment of prostate cancer].

    Lobel, B; Cipolla, B; Labrador, J

    1994-03-01

    Hormone dependence of prostate cancer is well known. In 80% of cases with metastases, hormone suppression leads to the reduction of tumour volume and related disorders. However the treatment is generally palliative because malignant process recurs after about around 16 months. Mean survival is less than 3 years in these forms. Lack of response come always together with a poor prognosis, and there is 90% mortality at 2 years. Advanced prostatic cancer should not be treated with hormones if the patient has few symptoms and his quality of life is satisfactory. Symptomatic forms require hormone manipulation. Orchidectomy or LH-RH are recommended. Total androgen ablation (combined treatment) leads rapidly to more relief of symptoms, but its drawbacks and especially high cost indicate that its use should be weighed individually. Estramustine is not a first-lune treatment. Presently, there is no criteria to predict response to treatment. PMID:8066398

  17. [Anorectal symptoms after prostate radiotherapy].

    Krol, R; Smeenk, R J; van Lin, E N J T; Hopman, W P M

    2015-01-01

    - Prostate cancer is the most common cancer in Dutch men and has a relatively good survival rate.- Anorectal symptoms after irradiation of the prostate, including rectal blood loss and faecal incontinence, can have a serious impact on quality of life.- On endoscopy, the Vienna Rectoscopy Score may reveal telangiectasia or other mucosal changes, but there may also be other causes of blood loss.- Endoscopy or watchful waiting can be considered in patients with rectal bleeding. Sucralfate enemas, argon plasma coagulation and hyperbaric oxygen therapy are effective treatments.- Increase in frequency of defaecation, faecal urgency or incontinence are related to decreased rectal compliance or to lowered anal resting pressure.- Dietary measures can be considered in patients with faecal urgency or incontinence, but scientific evidence for the effectiveness of this is marginal.- More accurate radiation techniques and the use of a spacer or endorectal balloon will probably contribute to maintaining rectal and anal function. PMID:26959731

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

    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

  19. Prostate stem cells and cancer

    Nikitin, Alexander Y.; Matoso, A; Roy-Burman, P

    2007-01-01

    Properties shared by neoplastic and stem cells indicate a possibility that somatic stem cells or transit-amplifying cells that have reacquired stem cell properties, particularly the ability for self-renewal, represent favorable targets for malignant transformation. In this review we discuss significance of the stem cell model for understanding prostate cancer pathogenesis and describe relevant studies in animals. It is proposed that dissemination of rare cancer stem ce...

  20. Approach to Oligometastatic Prostate Cancer.

    Bernard, Brandon; Gershman, Boris; Karnes, R Jeffrey; Sweeney, Christopher J; Vapiwala, Neha

    2016-01-01

    Oligometastatic prostate cancer has increasingly been recognized as a unique clinical state with therapeutic implications. It has been proposed that patients with oligometastases may have a more indolent course and that outcome may be further improved with metastasis-directed local ablative therapy. In addition, there are differing schools of thoughts regarding whether oligometastases represent isolated lesions-where targeted therapy may render a patient disease free-or whether they coexist with micrometastases, where targeted therapy in addition to systemic therapy is required for maximal clinical impact. As such, the approach to the patient with oligometastatic prostate cancer requires multidisciplinary consideration, with surgery, radiotherapy, and systemic therapy potentially of benefit either singularly or in combination. Indeed, mounting evidence suggests durable disease-free intervals and, in some cases, possibly cure, may be achieved with such a multimodal strategy. However, selecting patients that may benefit most from treatment of oligometastases is an ongoing challenge. Moreover, with the advent of new, highly sensitive imaging technologies, the spectrum based on CT of the abdomen and pelvis and technetium bone scan of localized to oligometastatic to widespread disease has become increasingly blurred. As such, new MRI- and PET-based modalities require validation. As some clinical guidelines advise against routine prostate-specific antigen screening, the possibility of more men presenting with locally advanced or de novo oligometastatic prostate cancer exists; thus, knowing how best to treat these patients may become more relevant at a population level. Ultimately, the arrival of prospective clinical data and better understanding of biology will hopefully further inform how best to treat men with this disease. PMID:27249693

  1. Prognostic factors in prostate cancer.

    Braeckman, Johan; Michielsen, Dirk

    2007-01-01

    In the nineteenth century the main goal of medicine was predictive: diagnose the disease and achieve a satisfying prognosis of the patient's chances. Today the effort has shifted to cure the disease. Since the twentieth century, the word prognosis has also been used in nonmedical contexts, for example in corporate finance or elections. The most accurate form of prognosis is achieved statistically. Based on different prognostic factors it should be possible to tell patients how they are expected to do after prostate cancer has been diagnosed and how different treatments may change this outcome. A prognosis is a prediction. The word prognosis comes from the Greek word (see text) and means foreknowing. In the nineteenth century this was the main goal of medicine: diagnose the disease and achieve a satisfying prognosis of the patient's chances. Today the effort has shifted towards seeking a cure. Prognostic factors in (prostate) cancer are defined as "variables that can account for some of the heterogeneity associated with the expected course and outcome of a disease". Bailey defined prognosis as "a reasoned forecast concerning the course, pattern, progression, duration, and end of the disease. Prognostic factors are not only essential to understand the natural history and the course of the disease, but also to predict possible different outcomes of different treatments or perhaps no treatment at all. This is extremely important in a disease like prostate cancer where there is clear evidence that a substantial number of cases discovered by prostate-specific antigen (PSA) testing are unlikely ever to become clinically significant, not to mention mortal. Furthermore, prognostic factors are of paramount importance for correct interpretation of clinical trials and for the construction of future trials. Finally, according to WHO national screening committee criteria for implementing a national screening programme, widely accepted prognostic factors must be defined before

  2. Prostate cancer outcome in Burkina Faso

    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.

  3. Extraglandular and intraglandular vascularization of canine prostate.

    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. PMID:14988915

  4. Pharmacological treatment of the benign prostatic hyperplasia

    Benign prostatic hyperplasia is a common disease in over 50 years-old men consisting in uncontrolled and benign growth of prostatic gland that leads to lower urinary tract symptoms. The etiology of benign prostatic hyperplasia is multifactoral involving the increased conversion of testosterone in dihydrotestosterone by the prostatic 5α-reductase action, which brought about events that encourage the prostate growth (static component) and the increase of the bladder and prostate smooth muscle tone (dynamic component) regulated by the aα1 -adrenoceptors (ADR). The pharmacological treatment of the benign prostatic hyperplasia includes the prostatic 5aα-reductase inhibitors, the aα1-adrenoreceptor blockers, their combined therapy and the phytotherapy. This paper was aimed at presenting the most relevant aspects of the pharmacology of drugs used for treating the benign prostatic hyperplasia, and providing elements to analyze their efficacy, safety and tolerability. To this end, a review was made of the different drugs for the treatment of this pathology and they were grouped according to their mechanism of action. Natural products were included as lipid extracts from Serenoa repens and Pygeum africanum as well as D-004, a lipid extract from Roystonea regia fruits, with proved beneficial effects on the main etiological factors of benign prostatic hyperplasia. D-004 is a prostatic 5a-reductase inhibitor, an aα1-adrenoceptor antagonist, aα 5-lipooxygenase inhibitor and has antioxidant action, all of which reveals a multifactoral mechanism. The results achieved till now indicate that D-004 is a safe and well-tolerated product

  5. Prostate radiation in non-metastatic castrate refractory prostate cancer provides an interesting insight into biology of prostate cancer

    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.

  6. Prostate radiation in non-metastatic castrate refractory prostate cancer provides an interesting insight into biology of prostate cancer

    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. 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. 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

  7. Aging Men and Prostate Cancer

    Thompson B

    2015-01-01

    Full Text Available Prostate cancer (PCa is one of the most commonly diagnosed cancers in men worldwide and its incidence increases with age, mainly affecting elderly men aged 60 and above. Factors known to be associated with the development and progression of PCa are age, family history, and race/ethnicity, with age being the most important factor. The reasons for the increased incidence and mortality due to prostate cancer in elderly men are not entirely clear. Continued exposure to environmental and dietary factors may lead to accumulation of genetic and epigenetic changes over the life-span, leading to altered expression and/or activity of tumor promoter and tumor suppressor genes. Changing levels of endogenous hormones (like androgens and metabolism in elderly men may also play a role in the development of prostate cancers which may be further influenced by testosterone replacement therapy. For many decades now preventative strategies and treatments such as radiation therapy or hormone therapy, and others have been administered to manage PCa; however current studies and evidence suggest that PCa is undertreated in elderly men, despite evidence of efficacy of these treatments, which leads to higher prevalence of mortality in this age group. Studies involving basic research, preventative and management strategies are still underway to understand the mechanisms of PCa development in elderly men and treatment of this disease in ageing male population.

  8. Nocturia and benign prostatic hyperplasia

    Laketić Darko

    2008-01-01

    Full Text Available Background/Aim. Nocturia often occurs in patients with benign prostate hyperplasia (BPH. The aim of the study was to investigate the frequency of nocturia in patients with BPH. Nocturia and other factors associated with it were also investigated. Methods. Forty patients with the confirmed diagnosis of BPH were studied. Transurethral and transvesical prostatectomy were performed in all the patients. Symptoms were evaluated with the International Prostate Symptom Score before, as well as three and six months after the surgery. All the results were compared with the control group. Results. There was no statistically significant difference between the patients before and after the surgery regarding nocturia. There was, however, a statistically significant difference between the operated patients and the control group regarding nocturia, as well as a statistically significant correlation between noctruia and the age of the patients in both the investigated and the control group. A correlation also existed between nocturia and the prostatic size. Conclusion. There was no statistically significant improvement in symptoms of nocturia after the surgery. It is necessary to be very careful in decision making in patients with nonabsolute indiction for surgery and isolated bothersome symptom of nocturia. Age of a patient should also be considered in the evaluation of favorable result of the surgery because of a significant correlation between noctura and the age of a patient.

  9. Antisense approaches in prostate cancer.

    Chi, Kim N; Gleave, Martin E

    2004-06-01

    Patients with hormone refractory prostate cancer have limited treatment options and new therapies are urgently needed. Advances in the understanding of the molecular mechanisms implicated in prostate cancer progression have identified many potential therapeutic gene targets that are involved in apoptosis, growth factors, cell signalling and the androgen receptor (AR). Antisense oligonucleotides are short sequences of synthetic modified DNA that are designed to be complimentary to a selected gene's mRNA and thereby specifically inhibit expression of that gene. The antisense approach continues to hold promise as a therapeutic modality to target genes involved in cancer progression, especially those in which the gene products are not amenable to small molecule inhibition or antibodies. The current status and future direction of a number of antisense oligonucleotides targeting several genes, including BCL-2, BCL-XL, clusterin, the inhibitors of apoptosis (IAP) family, MDM2, protein kinase C-alpha, c-raf, insulin-like growth factor binding proteins and the AR, that have potential clinical use in prostate cancer are reviewed. PMID:15174974

  10. ESUR prostate MR guidelines 2012

    Barentsz, Jelle O.; Fuetterer, Jurgen J. [Radboud University Nijmegen Medical Center, Department of Radiology, Nijmegen (Netherlands); Richenberg, Jonathan [Brighton and Sussex University Hospital Trust, Brighton (United Kingdom); Clements, Richard [Royal Gwent Hospital, Department of Clinical Radiology, Newport, South Wales (United Kingdom); Choyke, Peter [National Cancer Institute, Molecular Imaging Program, Bethesda, MD (United States); Verma, Sadhna [University Of Cincinnati Medical Center, Cincinnati, OH (United States); Villeirs, Geert [Ghent University Hospital, Division of Genitourinary Radiology, Ghent (Belgium); Rouviere, Olivier [Hopital Edouard Herriot, Hospices Civils de Lyon, Department of Urinary and Vascular Imaging, Lyon (France); Universite de Lyon, Lyon (France); Universite Lyon 1, Faculte de Medecine Lyon Est, Lyon (France); Logager, Vibeke [Copenhagen University, Hospital Herlev, Herlev (Denmark)

    2012-04-15

    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 for the optimal technique and three protocols for ''detection'', ''staging'' and ''node and bone'' are presented. The use of endorectal coil vs. pelvic phased array coil and 1.5 vs. 3 T is discussed. Clinical indications and a PI-RADS classification for structured reporting are presented. (orig.)

  11. Risk factors for prostatic inflammation extent and infection in benign prostatic hyperplasia

    Fa-Xian Yi; Qiang Wei; Hong Li; Xiang Li; Ming Shi; Qiang Dong; Yu-Ru Yang

    2006-01-01

    Aim: To investigate the risk factors for prostatic inflammation extent and infection in patients with benign prostatic hyperplasia (BPH) so as to manage prostatic inflammation more efficiently. Methods: Sixty patients with BPH undergoing TURP between September 2005 and December 2005 in West China Hospital of Sichuan University were studied. Prostate fluid (PF) was collected for the measurement of secretory IgA (SIgA) and complement 3 (C3).Prostate tissue were collected for testing bacterial 16S rDNA by real-time PCR, examining SIgA in the tissue and examining the inflammation. The possible clinical and immune risk factors for prostatic inflammation or infection were analyzed by using the logistic regression method. Results: Abnormal white blood cell count in urinalysis, prostatic infection and a high concentration of C3 in PF are the risk factors for prostatic inflammation extent (P = 0.025, 0.034 and 0.035, respectively and odds ratio [OR] = 18.269, 8.284 and 1.508, respectively). Risk factors for prostatic infection include the C3 concentration and the concentration of S IgA in PF (P = 0.003 and 0.013, respectively, and OR= 1.645 and 0.993, respectively). Conclusion: The present study suggests that prostatic inflammation is associated with urinary tract infection, prostatic infection and the activated complement and that prostatic infection is associated with the activated complement and downregulated mucosal immunity in prostates of the patients with BPH. It is also suggested that individual immune regulation should be considered in the treatment of prostatic inflammation and infection of patients with BPH.

  12. What's New in Prostate Cancer Research and Treatment?

    ... SEE A LIST » What’s new in prostate cancer research? Previous Topic Second cancers after prostate cancer Next Topic Additional resources for prostate cancer What’s new in prostate cancer research? Research into the causes , prevention , detection , and treatment ...

  13. Algorithms, nomograms and the detection of indolent prostate cancer

    M.J. Roobol-Bouts (Monique)

    2008-01-01

    textabstractPurpose: Prostate cancer is the most commonly diagnosed cancer in men. However, only about 12% of the men diagnosed with prostate cancer will die of their disease. Result: The serum PSA test can detect prostate cancers early, but using a PSA based cut-off indication for prostate biopsy r

  14. Primary Care of the Prostate Cancer Survivor.

    Noonan, Erika M; Farrell, Timothy W

    2016-05-01

    This summary of the American Cancer Society Prostate Cancer Survivorship Care Guidelines targets primary care physicians who coordinate care of prostate cancer survivors with subspecialists. Prostate cancer survivors should undergo prostate-specific antigen screening every six to 12 months and digital rectal examination annually. Surveillance of patients who choose watchful waiting for their prostate cancer should be conducted by a subspecialist. Any hematuria or rectal bleeding must be thoroughly evaluated. Prostate cancer survivors should be screened regularly for urinary incontinence and sexual dysfunction. Patients with predominant urge incontinence symptoms, which can occur after surgical and radiation treatments, may benefit from an anticholinergic agent. If there is difficulty with bladder emptying, a trial of an alpha blocker may be considered. A phosphodiesterase type 5 inhibitor can effectively treat sexual dysfunction following treatment for prostate cancer. Osteoporosis screening should occur before initiation of androgen deprivation therapy, and patients treated with androgen deprivation therapy should be monitored for anemia, metabolic syndrome, and vasomotor symptoms. Healthy lifestyle choices should be encouraged, including weight management, regular physical activity, proper nutrition, and smoking cessation. Primary care physicians should be vigilant for psychosocial distress, including depression, among prostate cancer survivors, as well as the potential impact of this distress on patients' family members and partners. PMID:27175954

  15. Effects of Prostate Cancer Screening and Treatment

    E.M. Wever (Elisabeth)

    2012-01-01

    textabstractProstate cancer is the second most frequently diagnosed cancer of men worldwide. The number of new cases worldwide was estimated at 899,000 and accounted for 13.6% of all cancers in men in 2008. With an estimated 258,000 deaths in 2008, prostate cancer is the sixth leading cause of death

  16. Prostate cancer is not breast cancer

    Ajit Venniyoor

    2016-01-01

    Full Text Available Cancers of the prostate and breast are hormone dependent cancers. There is a tendency to equate them and apply same algorithms for treatment. It is pointed out that metastatic prostate cancer with bone-only disease is a potentially fatal condition with a much poorer prognosis than metastatic breast cancer and needs a more aggressive approach.

  17. Early voiding dysfunction associated with prostate brachytherapy.

    Wagner; Nag; Young; Bahnson

    2000-12-15

    Introduction: Transperineal prostate brachytherapy is gaining popularity as a treatment for clinically localized carcinoma of the prostate. Very little prospective data exists addressing the issue of complications associated with this procedure. We present an analysis of the early voiding dysfunction associated with prostate brachytherapy. Materials and Methods: Forty-six consecutive patients who underwent Palladium-103 (Pd-103) seed placement for clinically localized prostate carcinoma were evaluated prospectively for any morbidity associated with the procedure. Twenty-three patients completed an International Prostate Symptom Score (IPSS) questionnaire preoperatively, at their first postoperative visit, and at their second postoperative visit. The total IPSS, each of the seven individual components, and the "bother" score were evaluated separately for each visit, and statistical significance was determined. Results: Urinary retention occurred in 7/46 patients (15%). Of these, 5 were able to void spontaneously after catheter removal. One patient is maintained with a suprapubic tube, and one patient is currently on continuous intermittent catheterization. Baseline IPSS was 7.1 and this went to 20.0 at the first postoperative visit (p<0.001). By the second postoperative visit, the IPSS was 8.0. Conclusions: In our experience, prostate brachytherapy for localized carcinoma of the prostate is associated with a 15% catheterization rate and a significant increase in the IPSS (7.1 to 20.0). This increase in the IPSS seems to be self-limited. Patients need to be educated on these issues prior to prostate brachytherapy. PMID:11113369

  18. Genomic rearrangements of PTEN in prostate cancer

    Sopheap ePhin

    2013-09-01

    Full Text Available The phosphatase and tensin homolog gene on chromosome 10q23.3 (PTEN is a negative regulator of the PIK3/Akt survival pathway and is the most frequently deleted tumor suppressor gene in prostate cancer. Monoallelic loss of PTEN is present in up to 60% of localized prostate cancers and complete loss of PTEN in prostate cancer is linked to metastasis and androgen independent progression. Studies on the genomic status of PTEN in prostate cancer initially used a two-color fluorescence in-situ hybridization (FISH assay for PTEN copy number detection in formalin fixed paraffin embedded tissue preparations. More recently, a four-color FISH assay containing two additional control probes flanking the PTEN locus with a lower false-positive rate was reported. Combined with the detection of other critical genomic biomarkers for prostate cancer such as ERG, AR, and MYC, the evaluation of PTEN genomic status has proven to be invaluable for patient stratification and management. Although less frequent than allelic deletions, point mutations in the gene and epigenetic silencing are also known to contribute to loss of PTEN function, and ultimately to prostate cancer initiation. Overall, it is clear that PTEN is a powerful biomarker for prostate cancer. Used as a companion diagnostic for emerging therapeutic drugs, FISH analysis of PTEN is promisingly moving human prostate cancer closer to more effective cancer management and therapies.

  19. FGF Signaling in Prostate Cancer Progression

    Nora M. NAVONE

    2009-01-01

    @@ Objective: prostate cancer is the second leading cause of cancer death in men in the United States. Localized prostate cancer can be cured by andro-gen ablation, but when the disease escapes the confines of the gland, the prospects for cure decrease drastically and the disease becomes "castrate resistant.

  20. Vietnam military service history and prostate cancer

    Fritschi Lin

    2006-03-01

    Full Text Available Abstract Background Three decades after US and Australian forces withdrew from Vietnam, there has been much public interest in the health consequences of service in Vietnam. One controversial question is whether the risk of prostate cancer amongst Vietnam veterans is increased. This paper examines relationships between military history, family history and risk of prostate cancer in a population-based case control study. Methods Cases were selected from the Cancer Registry of Western Australia as incident cases of histologically-confirmed prostate cancer, and controls were age-matched and selected from the Western Australian electoral roll. Study participants were asked to report any military service history and details about that service. Results Between January 2001 and September 2002, 606 cases and 471 controls aged between 40–75 years were recruited. An increased prostate cancer risk was observed in men reporting they were deployed in Vietnam although this was not statistically significant (OR = 2.12; 95% CI 0.88–5.06. An increased risk was also observed in men reporting prostate cancer in fathers (OR = 1.90; 95% CI 1.20–3.00 or brothers (OR = 2.05; 95% CI 1.20–3.50 diagnosed with prostate cancer. Conclusion These findings support a positive association between prostate cancer and military service history in the Vietnam war and a first degree relative family history of prostate cancer.

  1. Road to Recovery from Prostate Cancer

    Full Text Available ... that I work closely without our colleagues in plastic surgery and orthopedics and we are able to harvest ... of how you put the prostate in a plastic bad, which is locked. At the end of ... the port and remove the bag, which has contained the prostate in it. 00: ...

  2. Multiple prostatic abscesses presenting with urethral discharge.

    Gill, S. K.; Gilson, R. J.; Rickards, D

    1991-01-01

    Prostatic abscess has become less common, is now usually related to urinary tract infection, and is a rare cause of urethral discharge. The case is described of a man with prostatic abscesses caused by Staphylococcus aureus possibly related to recent skin abrasions. Transrectal ultrasound was used to make the diagnosis and to facilitate repeated drainage with a successful outcome.

  3. Sexuality in men after prostate cancer surgery

    Schantz Laursen, Birgitte

    2016-01-01

    INTRODUCTION: Prostate cancer affects a growing number of men. Although erectile dysfunction is a well-known side effect, its impact on sex life and sexuality is under-researched. PURPOSE: The aim of this study was therefore to elucidate the effect of surgical treatment for prostate cancer on men...

  4. Oxidative stress in prostate hypertrophy and carcinogenesis

    Waldemar M. Przybyszewski

    2009-07-01

    Full Text Available Aging, significant impairment of the oxidation/reduction balance, infection, and inflammation are recognized risk factors of benign hyperplasia and prostate cancer. Chronic symptomatic and asymptomatic prostate inflammatory processes generate significantly elevated levels of reactive oxygen and nitrogen species, and halogenated compounds. Prostate cancer patients showed significantly higher lipid peroxidation and lower antioxidant levels in peripheral blood than healthy controls, whereas patients with prostate hyperplasia did not show such symptoms. Oxidative/nitrosative/halogenative stress causes DNA modifications leading to genome instability that may initiate carcinogenesis; however, it was shown that oxidative damage alone is not sufficient to initiate this process. Peroxidation products induced by reactive oxygen and nitrogen species seem to take part in epigenetic mechanisms regulating genome activity. One of the most common changes occurring in more than 90�0of all analyzed prostate cancers is the silencing of GSTP1 gene activity. The gene encodes glutathione transferase, an enzyme participating in detoxification processes. Prostate hyperplasia is often accompanied by chronic inflammation and such a relationship was not observed in prostate cancer. The participation of infection and inflammation in the development of hyperplasia is unquestionable and these factors probably also take part in initiating the early stages of prostate carcinogenesis. Thus it seems that therapeutic strategies that prevent genome oxidative damage in situations involving oxidative/nitrosative/halogenative stress, i.e. use of antioxidants, plant steroids, antibiotics, and non-steroidal anti-inflammatory drugs, could help prevent carcinogenesis.

  5. Prostate cancer is not breast cancer

    Ajit Venniyoor

    2016-01-01

    Cancers of the prostate and breast are hormone dependent cancers. There is a tendency to equate them and apply same algorithms for treatment. It is pointed out that metastatic prostate cancer with bone-only disease is a potentially fatal condition with a much poorer prognosis than metastatic breast cancer and needs a more aggressive approach.

  6. Prostate-specific antigen (PSA) blood test

    ... for prostate cancer, such as ethnicity and family history Men at high risk may need to have more tests. These may include: Repeating your PSA test, most often sometime within 3 months A prostate biopsy A follow-up test called a free PSA ( ...

  7. Antitumor Effects of Saffron-Derived Carotenoids in Prostate Cancer Cell Models

    Claudio Festuccia

    2014-01-01

    Full Text Available Crocus sativus L. extracts (saffron are rich in carotenoids. Preclinical studies have shown that dietary intake of carotenoids has antitumor effects suggesting their potential preventive and/or therapeutic roles. We have recently reported that saffron (SE and crocin (CR exhibit anticancer activity by promoting cell cycle arrest in prostate cancer (PCa cells. It has also been demonstrated that crocetin esters are produced after SE gastrointestinal digestion by CR hydrolysis. The aim of the present report was to investigate if SE, crocetin (CCT, and CR affected in vivo tumor growth of two aggressive PCa cell lines (PC3 and 22rv1 which were xenografted in male nude mice treated by oral gavage with SE, CR, and CCT. We demonstrated that the antitumor effects of CCT were higher when compared to CR and SE and treatments reverted the epithelial-mesenchymal transdifferentiation (EMT as attested by the significant reduction of N-cadherin and beta-catenin expression and the increased expression of E-cadherin. Additionally, SE, CR, and CCT inhibited PCa cell invasion and migration through the downmodulation of metalloproteinase and urokinase expression/activity suggesting that these agents may affect metastatic processes. Our findings suggest that CR and CCT may be dietary phytochemicals with potential antitumor effects in biologically aggressive PCa cells.

  8. Prostate cancer in Denmark. Incidence, morbidity and mortality

    Brasso, K; Iversen, Peter

    1999-01-01

    Prostate cancer incidence and mortality rates in Denmark are reviewed for a 50-year period from 1943 to 1992. The prostate cancer incidence rate nearly tripled and prostate cancer mortality rate increased during this period. Until recently in Denmark the routine management of prostate cancer has...... been by deferred hormonal therapy. Morbidity and mortality associated with prostate cancer are analysed in a group of 1459 patients aged 55-74 years, who were diagnosed as having clinically localized prostate cancer in the 5-year period 1983 to 1987. In this group of patients prostate cancer is...

  9. Midline Prostatic Cyst Marsupialization Using Holmium Laser.

    Kilinc, Mehmet; Goger, Yunus Emre; Piskin, Mesut; Balasar, Mehmet; Kandemir, Abdulkadir

    2015-01-01

    Many of the prostatic cysts are asymptomatic and only 5% are symptomatic (Hamper et al., 1990; Higashi et al., 1990). These symptoms include pelvic pain, hematospermia, infertility, voiding dysfunction, prostatitis-like syndrome, and painful ejaculation. Treatment of prostatic cysts includes TRUSG guided drainage, endoscopic transurethral resection, and in some cases even open surgery. In the literature, endoscopic interventions use marsupialization of the midline prostatic cyst with transurethral resection (TUR) or transurethral incision with endoscopic urethrotomy (Dik et al., 1996; Terris, 1995). Holmium: YAG laser was employed for the marsupialization of the cyst wall in midline prostatic cyst treatment for the first time in the present study. Symptoms, treatment, and follow-up are presented in this paper. PMID:26101688

  10. Transrectal ultrasound study of prostatic lithiasis

    Prostatic lithiasis is a well know phenomenon. It has little clinical significance and is not easily shown by conventional radiography, which has poor sensitivity and specificity. The authors have studied 612 patients with both suprapubic and transrectal US in order to 1) assess US sensitivity and specificity and 2) report the frequency, spatial distribution, number and features of prostatic calcifications with special emphasis on differential diagnosis between prostatic neoplasms and chronic prostatitis. The authors have also studied the relationship between morphology and symptoms and the results agree with those reported in the scantly literature. The authors conclude that the parameters studied are directly related to age, except for a younger group with clear evidence of genital inflammation. The authors emphasize the impossibility to correlate morphology of prostatic calcifications with pathologic conditions: there are no specific symptoms clearly connected with calcification even though the inflammation is often associated with calcifications

  11. Vitamin D, Sunlight and Prostate Cancer Risk

    Krishna Vanaja Donkena

    2011-01-01

    Full Text Available Prostate cancer is the second common cancer in men worldwide. The prevention of prostate cancer remains a challenge to researchers and clinicians. Here, we review the relationship of vitamin D and sunlight to prostate cancer risk. Ultraviolet radiation of the sunlight is the main stimulator for vitamin D production in humans. Vitamin D's antiprostate cancer activities may be involved in the actions through the pathways mediated by vitamin D metabolites, vitamin D metabolizing enzymes, vitamin D receptor (VDR, and VDR-regulated genes. Although laboratory studies including the use of animal models have shown that vitamin D has antiprostate cancer properties, whether it can effectively prevent the development and/or progression of prostate cancer in humans remains to be inconclusive and an intensively studied subject. This review will provide up-to-date information regarding the recent outcomes of laboratory and epidemiology studies on the effects of vitamin D on prostate cancer prevention.

  12. Prostate biopsy tracking with deformation estimation

    Baumann, Michael; Daanen, Vincent; Troccaz, Jocelyne

    2011-01-01

    Transrectal biopsies under 2D ultrasound (US) control are the current clinical standard for prostate cancer diagnosis. The isoechogenic nature of prostate carcinoma makes it necessary to sample the gland systematically, resulting in a low sensitivity. Also, it is difficult for the clinician to follow the sampling protocol accurately under 2D US control and the exact anatomical location of the biopsy cores is unknown after the intervention. Tracking systems for prostate biopsies make it possible to generate biopsy distribution maps for intra- and post-interventional quality control and 3D visualisation of histological results for diagnosis and treatment planning. They can also guide the clinician toward non-ultrasound targets. In this paper, a volume-swept 3D US based tracking system for fast and accurate estimation of prostate tissue motion is proposed. The entirely image-based system solves the patient motion problem with an a priori model of rectal probe kinematics. Prostate deformations are estimated with ...

  13. [Prostate biopsy under magnetic resonance imaging guidance].

    Kuplevatskiy, V I; CherkashiN, M A; Roshchin, D A; Berezina, N A; Vorob'ev, N A

    2016-01-01

    Prostate cancer (PC) is one of the most important problems in modern oncology. According to statistical data, PC ranks second in the cancer morbidity structure in the Russian Federation and developed countries and its prevalence has been progressively increasing over the past decade. A need for early diagnosis and maximally accurate morphological verification of the diagnosis in difficult clinical cases (inconvenient tumor location for standard transrectal biopsy; gland scarring changes concurrent with prostatitis and hemorrhage; threshold values of prostate-specific antigen with unclear changes in its doubling per unit time; suspicion of biochemical recurrence or clinical tumor progression after special treatment) leads to revised diagnostic algorithms and clinically introduced new high-tech invasive diagnostic methods. This paper gives the first analysis of literature data on Russian practice using one of the new methods to verify prostate cancer (transrectal prostate cancer under magnetic resonance imaging (MRI) guidance). The have sought the 1995-2015 data in the MEDLINE and Pubmed. PMID:27192773

  14. Potency after permanent prostate brachytherapy for localized prostate cancer

    Purpose: The evaluation of potency preservation after treatment of localized prostate cancer with transperineal permanent prostate brachytherapy (PPB) and the efficacy of sildenafil were studied. Methods and Materials: This study comprised 482 patients who were able to maintain an erection suitable for intercourse before treatment from a cohort of 1166 patients with clinically localized prostate cancer treated with PPB. All patients have been followed prospectively, and actuarial analysis was performed to assess potency preservation over time. Patients treated with sildenafil were evaluated as to its efficacy. Results: The median follow-up of this cohort was 34 months (6-92), with a median age of 68 years (47-80). Potency was preserved in 311 of the 482 patients, with a 5-year actuarial potency rate of 52.7%. The 5-year actuarial potency rate for patients treated with PPB as monotherapy was 76%, and, for those treated with combination external beam radiotherapy (EBT) + PPB, 56% (p=0.08). Patients treated with neoadjuvant androgen deprivation (NAAD) + PPB had a 5-year potency rate of 52%, whereas those with combination EBT + PPB + NAAD had a potency rate of 29% (p=0.13). Cox regression analysis identified that pretreatment use of NAAD and patient age predicted for impotence (p=0.0001 and 0.04, respectively). Of 84 patients treated with sildenafil, 52 had a successful outcome (62%). The response to sildenafil was significantly better in those patients not treated with NAAD (p=0.04). Conclusions: The actuarial potency rates at 5 years for patients treated with PPB are lower than generally acknowledged, except for those patients treated with PPB as monotherapy. Patients who received sildenafil exhibited improved potency in a majority of cases

  15. TUMOR MARKERS IN BONE MARROW IN PATIENTS WITH PROSTATIC CANCER

    Iwai, Akio; Ozono, Seiichiro; Tanaka, Yozo; Nagayoshi, Junichi; Hirayama, Akihide; Kumon, Toshihiko; Joko, Masanori; Hirata, Naoya; Yoshikawa, Motoyoshi; Tabata, Shoichi; Uemura, Hirotsugu; Moriya, Akira; Kaneko, Yoshiteru; Okamoto, Shinji; Hirao, Yoshihiko

    1991-01-01

    We compared prostatic specific acid phosphatase (PAP), prostatic specificantigen (PA) and γ-seminoprotein (γ-SM) levels between bone marrow and serum for the purpose of assessing of the usefulness of these tumor markers in early detection ofbone metastasis in cases with prostatic cancer. Thirty-three patients were entered into this study. Of the patients, 20 had prostatic cancer including 11 with bone metastasis, and 13 patients had benign prostatic hypertrophy (BPH) served as controls. It se...

  16. Focal therapy for prostate cancer: The current status

    Marshall, Susan; Taneja, Samir

    2015-01-01

    Purpose In an era of increasing prostate cancer incidence and earlier detection, the assessment of clinical significance of prostate cancer is critical. Minimally invasive therapies are increasingly being investigated in localized prostate cancer. Methods and results In this review, we discuss the current status of magnetic resonance imaging targeted fusion prostate biopsy and focal therapy for prostate cancer, its rationale, and techniques. Conclusion Focal therapy offers a promising outlook...

  17. Activation of the hedgehog pathway in advanced prostate cancer

    McCormick Frank; Chen Kai; He Nonggao; Chi Sumin; Zhang Xiaoli; Li Chengxin; Sheng Tao; Gatalica Zoran; Xie Jingwu

    2004-01-01

    Abstract Background The hedgehog pathway plays a critical role in the development of prostate. However, the role of the hedgehog pathway in prostate cancer is not clear. Prostate cancer is the second most prevalent cause of cancer death in American men. Therefore, identification of novel therapeutic targets for prostate cancer has significant clinical implications. Results Here we report that activation of the hedgehog pathway occurs frequently in advanced human prostate cancer. We find that ...

  18. Prostate Boundary Detection from Ultrasound Images using Ant Colony Optimization

    Vikas Wasson; Baljit Singh

    2011-01-01

    Prostate Cancer & diseases is quite common in elderly men. Early detection of prostate cancer is very essential for the success of treatment. In the diagnosis & treatment of prostate diseases, prostate boundary detection from sonography images plays a key role. However, because of the poor image quality of ultra sonograms, prostate boundary detection is still difficult & challenging task & no efficient & consistent solution has yet been found. For improving the efficiency, they need is ...

  19. Redefining Hormone Sensitive Disease in Advanced Prostate Cancer

    Xiaoyu Hou; Flaig, Thomas W.

    2012-01-01

    Prostate cancer is the most common cancer among men in the United States. For decades, the cornerstone of medical treatment for advanced prostate cancer has been hormonal therapy, intended to lower testosterone levels, known as Androgen Deprivation Therapy (ADT). The development of hormone-resistant prostate cancer (now termed castration-resistant prostate cancer:CRPC) remains the key roadblock in successful long-term management of prostate cancer. New advancements in medical therapy for pros...

  20. The Role of Estrogen Receptor β in Prostate Cancer

    Christoforou, Paraskevi; Christopoulos, Panagiotis F; Koutsilieris, Michael

    2014-01-01

    Although androgen receptor (AR) signaling is the main molecular tool regulating growth and function of the prostate gland, estrogen receptor β (ERβ) is involved in the differentiation of prostatic epithelial cells and numerous antiproliferative actions on prostate cancer cells. However, ERβ splice variants have been associated with prostate cancer initiation and progression mechanisms. ERβ is promising as an anticancer therapy and in the prevention of prostate cancer. Herein, we review the re...

  1. Dietary Zinc and Prostate Cancer in the TRAMP Mouse Model

    Prasad, Ananda S; Mukhtar, Hasan; Beck, Frances W.J.; Adhami, Vaqar M.; Siddiqui, Imtiaz A.; Din, Maria; Hafeez, Bilal B.; KUCUK, Omer

    2010-01-01

    Circumstantial evidence indicates that zinc may have an important role in the prostate. Total zinc levels in the prostate are 10 times higher than in other soft tissues. Zinc concentrations in prostate epithethial cancer cells are decreased significantly. Zinc supplementation for prevention and treatment of prostate cancer in humans has yielded controversial results. No studies have been reported in animal models to show the effect of zinc supplementation on prevention of prostate cancer, thu...

  2. The role of Estrogen Receptor Beta in Prostate Cancer.

    Christoforou, Paraskevi; Christopoulos, Panagiotis F; Koutsilieris, Michael

    2014-01-01

    Although androgen receptor (AR) signaling is the main molecular tool regulating growth and function of prostate gland, estrogen receptor beta (ERβ) is involved contributive in the differentiation of prostatic epithelial cells and numerous antiproliferative actions on prostate cancer cells. However, ERβ splice variants have been associated with prostate cancer initiation and progression mechanisms. Nowadays, ERß is a promising target as an anticancer therapy and prevention for prostate cancer....

  3. Behavioral stress accelerates prostate cancer development in mice

    Hassan, Sazzad; Karpova, Yelena; Baiz, Daniele; Yancey, Dana; Pullikuth, Ashok; Flores, Anabel; Register, Thomas; Cline, J. Mark; D’Agostino, Ralph; Danial, Nika; Datta, Sandeep Robert; Kulik, George

    2013-01-01

    Prostate cancer patients have increased levels of stress and anxiety. Conversely, men who take beta blockers, which interfere with signaling from the stress hormones adrenaline and noradrenaline, have a lower incidence of prostate cancer; however, the mechanisms underlying stress–prostate cancer interactions are unknown. Here, we report that stress promotes prostate carcinogenesis in mice in an adrenaline-dependent manner. Behavioral stress inhibited apoptosis and delayed prostate tumor invol...

  4. Drugs reverting multidrug resistance (chemosensitizers)

    Gualtieri, F. [Florence Univ. (Italy). Dip. di Scienze Farmaceutiche

    1996-12-01

    Drug resistance is a phenomenon that frequently impairs proper treatment of cancer. Multidrug resistance (MDR) is a particular case of acquired drug resistance, resulting from overexpression of a protein (P-170) that functions as a pump, clearing cells from the chemotherapic. The P-170 protein functions can be inhibited by a variety of lipophilic drugs containing a hydrophilic nitrogen, protonated at physiological pH. A considerable effort is underway to identify new drugs able to reverse MDR. Few of these molecules are already undergoing clinical trials.

  5. Identifying Small Mean Reverting Portfolios

    d'Aspremont, Alexandre

    2007-01-01

    Given multivariate time series, we study the problem of forming portfolios with maximum mean reversion while constraining the number of assets in these portfolios. We show that it can be formulated as a sparse canonical correlation analysis and study various algorithms to solve the corresponding sparse generalized eigenvalue problems. After discussing penalized parameter estimation procedures, we study the sparsity versus predictability tradeoff and the impact of predictability in various mar...

  6. Functional cure of SIVagm infection in rhesus macaques results in complete recovery of CD4+ T cells and is reverted by CD8+ cell depletion.

    Ivona Pandrea

    2011-08-01

    Full Text Available Understanding the mechanism of infection control in elite controllers (EC may shed light on the correlates of control of disease progression in HIV infection. However, limitations have prevented a clear understanding of the mechanisms of elite controlled infection, as these studies can only be performed at randomly selected late time points in infection, after control is achieved, and the access to tissues is limited. We report that SIVagm infection is elite-controlled in rhesus macaques (RMs and therefore can be used as an animal model for EC HIV infection. A robust acute infection, with high levels of viral replication and dramatic mucosal CD4(+ T cell depletion, similar to pathogenic HIV-1/SIV infections of humans and RMs, was followed by complete and durable control of SIVagm replication, defined as: undetectable VLs in blood and tissues beginning 72 to 90 days postinoculation (pi and continuing at least 4 years; seroreversion; progressive recovery of mucosal CD4(+ T cells, with complete recovery by 4 years pi; normal levels of T cell immune activation, proliferation, and apoptosis; and no disease progression. This "functional cure" of SIVagm infection in RMs could be reverted after 4 years of control of infection by depleting CD8 cells, which resulted in transient rebounds of VLs, thus suggesting that control may be at least in part immune mediated. Viral control was independent of MHC, partial APOBEC restriction was not involved in SIVagm control in RMs and Trim5 genotypes did not impact viral replication. This new animal model of EC lentiviral infection, in which complete control can be predicted in all cases, permits research on the early events of infection in blood and tissues, before the defining characteristics of EC are evident and when host factors are actively driving the infection towards the EC status.

  7. Gossypol induces apoptosis by activating p53 in prostate cancer cells and prostate tumor-initiating cells

    Volate, Suresh R.; Kawasaki, Brian T.; Hurt, Elaine M.; Milner, John A.; Kim, Young S.; White, Jeffrey; Farrar, William L.

    2010-01-01

    Prostate cancer (PCa) continues to represent a burgeoning medical problem in the United States. Recent studies suggest that gossypol, a bioactive phytochemical produced by cotton plants, is a promising agent against prostate cancer. The current studies were undertaken to examine the chemotherapeutic efficacy of gossypol on human prostate cancer cell lines and prostate tumor-initiating cells (pTICs). Gossypol reduced viability of three prostate cancer cell lines (LAPC4, PC3, and DU145) with an...

  8. File list: Pol.Prs.05.AllAg.Prostatic_Neoplasms [Chip-atlas[Archive

    Full Text Available Pol.Prs.05.AllAg.Prostatic_Neoplasms mm9 RNA polymerase Prostate Prostatic Neoplasms... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Prs.05.AllAg.Prostatic_Neoplasms.bed ...

  9. File list: His.Prs.50.AllAg.Prostatic_Neoplasms [Chip-atlas[Archive

    Full Text Available His.Prs.50.AllAg.Prostatic_Neoplasms mm9 Histone Prostate Prostatic Neoplasms http:...//dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Prs.50.AllAg.Prostatic_Neoplasms.bed ...

  10. File list: Unc.Prs.20.AllAg.Prostatic_Neoplasms [Chip-atlas[Archive

    Full Text Available Unc.Prs.20.AllAg.Prostatic_Neoplasms mm9 Unclassified Prostate Prostatic Neoplasms ...http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Prs.20.AllAg.Prostatic_Neoplasms.bed ...

  11. File list: Pol.Prs.50.AllAg.Prostatic_Neoplasms [Chip-atlas[Archive

    Full Text Available Pol.Prs.50.AllAg.Prostatic_Neoplasms mm9 RNA polymerase Prostate Prostatic Neoplasms... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Prs.50.AllAg.Prostatic_Neoplasms.bed ...

  12. File list: His.Prs.05.AllAg.Prostatic_Neoplasms [Chip-atlas[Archive

    Full Text Available His.Prs.05.AllAg.Prostatic_Neoplasms mm9 Histone Prostate Prostatic Neoplasms http:...//dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Prs.05.AllAg.Prostatic_Neoplasms.bed ...

  13. File list: Unc.Prs.10.AllAg.Prostatic_Neoplasms [Chip-atlas[Archive

    Full Text Available Unc.Prs.10.AllAg.Prostatic_Neoplasms mm9 Unclassified Prostate Prostatic Neoplasms ...http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Prs.10.AllAg.Prostatic_Neoplasms.bed ...

  14. File list: Unc.Prs.05.AllAg.Prostatic_Neoplasms [Chip-atlas[Archive

    Full Text Available Unc.Prs.05.AllAg.Prostatic_Neoplasms mm9 Unclassified Prostate Prostatic Neoplasms ...http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Prs.05.AllAg.Prostatic_Neoplasms.bed ...

  15. File list: His.Prs.10.AllAg.Prostatic_Neoplasms [Chip-atlas[Archive

    Full Text Available His.Prs.10.AllAg.Prostatic_Neoplasms mm9 Histone Prostate Prostatic Neoplasms http:...//dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Prs.10.AllAg.Prostatic_Neoplasms.bed ...

  16. File list: Unc.Prs.50.AllAg.Prostatic_Neoplasms [Chip-atlas[Archive

    Full Text Available Unc.Prs.50.AllAg.Prostatic_Neoplasms mm9 Unclassified Prostate Prostatic Neoplasms ...http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Prs.50.AllAg.Prostatic_Neoplasms.bed ...

  17. File list: His.Prs.20.AllAg.Prostatic_Neoplasms [Chip-atlas[Archive

    Full Text Available His.Prs.20.AllAg.Prostatic_Neoplasms mm9 Histone Prostate Prostatic Neoplasms http:...//dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Prs.20.AllAg.Prostatic_Neoplasms.bed ...

  18. File list: Pol.Prs.20.AllAg.Prostatic_Neoplasms [Chip-atlas[Archive

    Full Text Available Pol.Prs.20.AllAg.Prostatic_Neoplasms mm9 RNA polymerase Prostate Prostatic Neoplasms... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Prs.20.AllAg.Prostatic_Neoplasms.bed ...

  19. Prostate Cancer: Symptoms, Diagnosis and Treatment | NIH MedlinePlus the Magazine

    ... this page please turn Javascript on. Feature: Prostate Cancer Prostate Cancer: Symptoms, Diagnosis and Treatment Past Issues / Winter 2010 ... only way to confirm a diagnosis of prostate cancer. Treatment Prostate cancer treatment depends on how serious the cancer ...

  20. File list: Pol.Prs.10.AllAg.Prostatic_Neoplasms [Chip-atlas[Archive

    Full Text Available Pol.Prs.10.AllAg.Prostatic_Neoplasms mm9 RNA polymerase Prostate Prostatic Neoplasms... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Prs.10.AllAg.Prostatic_Neoplasms.bed ...

  1. Image guided prostate cancer treatments

    Bard, Robert L. [Bard Cancer Center, Biofoundation for Angiogenesis Research and Development, New York, NY (United States); Fuetterer, Jurgen J. [Radboud Univ. Nijmegen, Medical Centre (Netherlands). Dept. of Radiology; Sperling, Dan (ed.) [Sperling Prostate Center, Alpha 3TMRI, New York, NY (United States)

    2014-07-01

    Systematic overview of the application of ultrasound and MRI in the diagnosis and treatment of diseases of the lower urinary tract. Detailed information on image-guided therapies, including focused ultrasound, photodynamic therapy, and microwave and laser ablation. Numerous high-quality illustrations based on high-end equipment. Represents the state of the art in Non Invasive Imaging and Minimally Invasive Ablation Treatment (MIAT). Image-Guided Prostate Cancer Treatments is a comprehensive reference and practical guide on the technology and application of ultrasound and MRI in the male pelvis, with special attention to the prostate. The book is organized into three main sections, the first of which is devoted to general aspects of imaging and image-guided treatments. The second section provides a systematic overview of the application of ultrasound and MRI to the diagnosis and treatment of diseases of the lower urinary tract. Performance of the ultrasound and MRI studies is explained, and the normal and abnormal pathological anatomy is reviewed. Correlation with the ultrasound in the same plane is provided to assist in understanding the MRI sequences. Biopsy and interventional procedures, ultrasound-MRI fusion techniques, and image-guided therapies, including focused ultrasound, photodynamic therapy, microwave and laser ablation, are all fully covered. The third section focuses on securing treatment effectiveness and the use of follow-up imaging to ensure therapeutic success and detect tumor recurrence at an early stage, which is vital given that prompt focal treatment of recurrence is very successful. Here, particular attention is paid to the role of Doppler ultrasound and DCE-MRI technologies. This book, containing a wealth of high-quality illustrations based on high-end equipment, will acquaint beginners with the basics of prostate ultrasound and MRI, while more advanced practitioners will learn new skills, means of avoiding pitfalls, and ways of effectively

  2. MR imaging of prostate cancer

    Accurate diagnosis and staging of prostate cancer (PC) is developing into an important health care issue in light of the high incidence of PC and the improvements in stage-adapted therapy. The purpose of this paper is to provide an overview on the current role of MR imaging and MR spectroscopy in the diagnosis and staging of PC.Material and methods Pertinent literature was searched and evaluated to collect information on current clinical indications, study techniques, diagnostic value, and limitations of magnetic resonance imaging and spectroscopy. Major indications for MR imaging of patients with supected PC are to define tumor location before biopsy when clinical or TRUS findings are inconclusive, and to provide accurate staging of histologically proven PC to ascertain effective therapy. Current MR imaging techniques for the evaluation of PC include multiplanar high-resolution T2-weighted FSE and T1-weighted SE sequences using combined endorectal and phased-array coils. Using these techniques, the reported accuracy of MR imaging for the diagnosis of extracapsular tumor extension ranges between 82 and 88% with sensitivities between 80 and 95%, and specificities between 82 and 93%. Typical MR findings of PC in different stages of disease, as well as diagnostic problems, such as chronic prostatitis, biopsy-related hemorrhage and therapy-related changes of prostatic tissue are discussed. In addition, the current perspectives and limitations of MR spectroscopy in PC are summarized. Current MR imaging techniques provide important diagnostic information in the pretherapeutic workup of PC including a high staging accuracy, and is superior to TRUS. (orig.)

  3. Image guided prostate cancer treatments

    Systematic overview of the application of ultrasound and MRI in the diagnosis and treatment of diseases of the lower urinary tract. Detailed information on image-guided therapies, including focused ultrasound, photodynamic therapy, and microwave and laser ablation. Numerous high-quality illustrations based on high-end equipment. Represents the state of the art in Non Invasive Imaging and Minimally Invasive Ablation Treatment (MIAT). Image-Guided Prostate Cancer Treatments is a comprehensive reference and practical guide on the technology and application of ultrasound and MRI in the male pelvis, with special attention to the prostate. The book is organized into three main sections, the first of which is devoted to general aspects of imaging and image-guided treatments. The second section provides a systematic overview of the application of ultrasound and MRI to the diagnosis and treatment of diseases of the lower urinary tract. Performance of the ultrasound and MRI studies is explained, and the normal and abnormal pathological anatomy is reviewed. Correlation with the ultrasound in the same plane is provided to assist in understanding the MRI sequences. Biopsy and interventional procedures, ultrasound-MRI fusion techniques, and image-guided therapies, including focused ultrasound, photodynamic therapy, microwave and laser ablation, are all fully covered. The third section focuses on securing treatment effectiveness and the use of follow-up imaging to ensure therapeutic success and detect tumor recurrence at an early stage, which is vital given that prompt focal treatment of recurrence is very successful. Here, particular attention is paid to the role of Doppler ultrasound and DCE-MRI technologies. This book, containing a wealth of high-quality illustrations based on high-end equipment, will acquaint beginners with the basics of prostate ultrasound and MRI, while more advanced practitioners will learn new skills, means of avoiding pitfalls, and ways of effectively

  4. Multiparametric MRI in Prostate Cancer

    Tarık Esen; Barıs Turkbey; Anup Patel; Jurgen Futterer

    2014-01-01

    Editorial Multiparametric MRI in Prostate Cancer TarJk Esen,1 BarJs Turkbey,2 Anup Patel,3 and Jurgen Futterer4 1 Department of Urology, School of Medicine, Koc University, 34450 Istanbul, Turkey 2Molecular Imaging Program, NCI, NIH, Bethesda, MD 20892, USA 3Royal London Hospital, Barts Health NHS Trust, London E1 1BB,UK 4Department of Radiology, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands Correspondence should be addressed to Tarık Esen;...

  5. Shared care in prostate cancer

    Lund, Anette Svarre; Lund, Lars; Jønler, Morten;

    2016-01-01

    OBJECTIVE: The aim of this study was to investigate 3 year follow-up in patients with stable prostate cancer (PCa) managed in a shared care program by general practitioners (GPs) in collaboration with urological departments. PCa patients who have undergone curative treatment or endocrine therapy...... require long-term follow-up. Until recently, follow-up has primarily been managed by urologists at hospital-based outpatient clinics. However, new organizational strategies are needed to meet the needs of the growing number of elderly, comorbid cancer patients. These new organizational strategies target...

  6. [Prostate cancer and metabolic syndrome].

    Nagamatsu, Hirotaka; Teishima, Jun; Inoue, Shogo; Hayashi, Tetsutaro; Matsubara, Akio

    2016-01-01

    The prevalence of metabolic syndrome (MS) is increasing in Japan because of westernization of diet and lifestyle. Previous epidemiological studies have demonstrated MS to relate with the malignant potential of prostate cancer (PCa) while its relationship to the risk of PCa has been still controversial. Several pathologies involved in MS, such as insulin resistance, abnormality of secreted adipokines, chronic inflammation, alteration of sex hormones, have been reported to affect the progression of PCa. Based on these evidences, clinical studies for PCa patients have been tried for suppressing the progression of PCa through the management of MS. PMID:26793896

  7. Prostatic carcinoma in two cats

    Clinical, radiological and pathological features of two cats with prostatic carcinoma are reported. In both cats the presenting history included signs of lower urinary tract disease with haematuria and dysuria. Prostatomegaly was visible radiographically in one cat; an irregular intraprostatic urethra was seen on retrograde contrast urethrography in both cats. In one of the cats, neoplasia was suspected on the basis of a transurethral catheter biopsy. Following a poor response to palliative treatment in both cases, euthanasia was performed with histological confirmation of the diagnosis

  8. MRI & MR SPECTROSCOPIC EVALUATION OF PROSTATIC CARCINOMA

    Rupak

    2015-09-01

    Full Text Available BACKGROUND : Prostate cancer is the most common malignancy among men more than fifty years of age (Cancer foundation of India. Imaging may help in clarifying several important issues in localized prostate cancer. MRI provides the best depiction of the contours of the prostate as well as its internal zonal anatomy. Recent evidence suggests that multi - parametric MRI could improve the accuracy of diagnostic assessment in prostate cancer. In addition, MRI also allows functional assessment with techniques such as diffusion - weighted MRI (DWI, MR spectroscopy (MRS, and dynamic contrast enhanced MRI (DCE - MRI. Strong opinions are held about the need for endorectal coil imaging. Endorectal coils provide large gains in signal with reductions in noise, most noticeably at 1.5 T; however, endorectal coils are uncomfortable and expensive. At 3 T, the need for endorectal coils has been debated. Clearly, the highest - quality MRI results from the combined use of endorectal coils and phased array body coils at 3 T. Prostate cancer is associated with proportionately lower levels of citrate and higher levels of choline and creatine than are seen in benign prostatic hyperplasia (BPH or in normal prostate tissu e. This difference can be detected by magnetic resonance spectroscopic imaging (MRSI. MRSI uses a strong magnetic field to obtain metabolic information (spectra that identifies the relative concentrations of various metabolites in the cell cytoplasm and the extracellular space. This technique can identify metabolic differences in prostate tissue (BPH, prostate cance r, and normal prostate tissue. AIM: To evaluate the role of MRI and MR Spectroscopy in the diagnosis of prostatic carcinoma by pelvic phased array coil in the detection of prostatic carcinoma in men with Prostatomegaly & elevated PSA levels and establishing statistical analysis of the same. METHOD: A prospective study of minimum 50 consecutive cases with Prostatomegaly & raised PSA levels

  9. [Treatment strategies for advanced prostate cancer].

    Küronya, Zsófia; Bíró, Krisztina; Géczi, Lajos; Németh, Hajnalka

    2015-09-01

    There has been dramatic improvement in the diagnosis and treatment of prostate cancer recently. The treatment of localized disease became more successful with the application of new, sophisticated techniques available for urologic surgeons and radiotherapists. Nevertheless a significant proportion of patients relapses after the initial local treatment or is diagnosed with metastatic disease at the beginning. In the past five years, six new drugs became registered for the treatment of metastatic, castration-resistant prostate cancer, such as sipuleucel-T, cabazitaxel, abiraterone, enzalutamide, the α-emitting radionuclide alpharadin and the receptor activator of nuclear factor kappa-B (RANK) ligand inhibitor denosumab. The availability of these new treatment options raises numerous questions. In this review we present the standard of care of metastatic prostate cancer by disease stage (hormone naive/ hormone sensitive metastatic prostate cancer, non-metastatic castration-resistant prostate cancer, oligometastatic/multimetastatic castration-resistant prostate cancer) and the emerging treatment modalities presently assessed in clinical trials. We would also like to give advice on debatable aspects of the management of metastatic prostate cancer. PMID:26339912

  10. New discoveries in prostate cancer pathogenesis

    Background. Through PSA screening the rate of prostate cancers detected at an early stage has increased significantly; thus a decrease in mortality can be expected in the near future. Despite all scientific efforts, however, the molecular mechanisms underlying the development and progression of prostate cancer remain poorly understood. Prostate cancer is a disease of aging men and epidemiological evidence supports a major contribution to its development through diet, lifestyle and environmental factors. Genetic instability is the basic phenomenon of tissue cell cancerisation. This instability can be hereditary or due to mutations and other chromosomal aberrations acquired during life. In recent years a large number of interesting data have been collected which show the relationships between focal atrophy and genetic instability of the prostate epithelia. Atrophy can be the result of prostatitis, ischemia as well as of oxidative stress (diet). Several chromosomal aberrations typical for prostate cancer (loss of 8p22; gain of 8q24 and X) can be already detected in the epithelia of the atrophic areas. Moreover also the deactivation of a gene (GSTP1) which encodes a carcinogene-detoxification enzyme has been found in such epithelia. Conclusions. Molecular pathology is slowly revealing the links which exist among age, atherosclerosis and oxidative stress (diet), inflammation and the pathogenesis of prostate cancer. In the near future perhaps this knowledge will enable us to actively prevent this most common malignancy of elderly men. (author)

  11. Statin Use in Prostate Cancer: An Update

    Babcook, Melissa A.; Joshi, Aditya; Montellano, Jeniece A.; Shankar, Eswar; Gupta, Sanjay

    2016-01-01

    3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, known as statins, are commonly prescribed for the treatment of hypercholesterolemia and cardiovascular disease. A systematic review was conducted using the keywords “statin and prostate cancer” within the title search engines including PubMed, Web of Science, and the Cochrane Library for relevant research work published between 2004 and December 2015. Although still premature, accumulating clinical evidence suggests that statin use may be beneficial in the prevention and/or treatment of prostate cancer. These human studies consist of meta-analyses of secondary endpoints obtained from randomized, controlled cardiovascular disease clinical trials of statins, patient database, observational studies, and a few, small case–control studies, directly addressing statin use on prostate cancer pathology and recurrence. This review summarizes and discusses the recent clinical literature on statins and prostate cancer with a recommendation to move forward with randomized, placebo-controlled clinical trials, investigating the use of statins. Additional preclinical testing of statins on prostate cancer cell lines and in vivo models is needed to elucidate pathways and determine its efficacy for prevention and/or treatment of prostate cancer, more specifically, the difference in the effectiveness of lipophilic versus hydrophilic statins in prostate cancer. PMID:27441003

  12. Advances in MRI diagnosis of prostate cancer

    Prostate cancer is the second most common cancer in the world, and the incidence of prostate cancer in China shows an upward trend. MRI has high soft tissue resolution and multi-dimensional imaging advantages, and it can better show the anatomy of the prostate and adjacent tissue structures. With the development of MR technique, it plays a more and more important role in prostate cancer diagnosis. This review starts from the imaging performance of routine MRI sequence of prostate cancer, and a variety of functional MRI applications in the diagnosis and differential diagnosis of prostate cancer are described in detail, such as MR perfusion-weighted imaging, MR spectroscopy, MR diffusion-weighted imaging, MR diffusion tensor imaging, intravoxel incoherent motion diffusion-weighted imaging, MR susceptibility-weighted imaging. Meanwhile this review introduces that functional MRI has more advantages and can provide more image information than routine MRI sequence. According to a series of semi-quantitative and quantitative data, functional MRI can further provide the blood perfusion of prostate cancer, water molecule diffusion and microcirculation state, metabolism and biochemical composition change information. (authors)

  13. Progress in gene therapy for prostate cancer

    KamranAliAhmed

    2012-11-01

    Full Text Available Gene therapy has held promise to correct various disease processes. Prostate cancer represents the second leading cause of cancer death in American men. A number of clinical trials involving gene therapy for the treatment of prostate cancer have been reported. The ability to efficiently transduce tumors with effective levels of therapeutic genes has been identified as a fundamental barrier to effective cancer gene therapy. The approach utilizing gene therapy in prostate cancer patients at our institution attempts to address this deficiency. The sodium-iodide symporter (NIS is responsible for the ability of the thyroid gland to transport and concentrate iodide. The characteristics of the NIS gene suggest that it could represent an ideal therapeutic gene for cancer therapy. Published results from Mayo Clinic researchers have indicated several important successes with the use of the NIS gene and prostate gene therapy. Studies have demonstrated that transfer of the human NIS gene into prostate cancer using adenovirus vectors in vitro and in vivo results in efficient uptake of radioactive iodine and significant tumor growth delay with prolongation of survival. Preclinical successes have culminated in the opening of a phase I trial for patients with advanced prostate disease which is currently accruing patients. Further study will reveal the clinical promise of NIS gene therapy in the treatment of prostate as well as other malignancies.

  14. Prostate Cancer Detection at Rebiopsy After an Initial Benign Diagnosis: Results Using Sextant Extended Prostate Biopsy

    Katia Ramos Moreira Leite; Luiz Heraldo Camara-Lopes; José Cury; Marcos F. Dall'Oglio; Adriana Sañudo; Miguel Srougi

    2008-01-01

    INTRODUCTION: Sextant prostate biopsy remains the standard technique for the detection of prostate cancer. It is well known that after a diagnosis of small acinar proliferation (ASAP) or high grade prostate intraepithelial neoplasia (HGPIN), the possibility of finding cancer is approximately 40% and 30%, respectively. OBJECTIVE: We aim to analyze follow-up biopsies on patients who initially received a benign diagnosis after exclusion of HGPIN and ASAP. METHODS: From July 2000 to December 2003...

  15. Focal Therapy in the Management of Prostate Cancer: An Emerging Approach for Localized Prostate Cancer

    Takeo Nomura; Hiromitsu Mimata

    2012-01-01

    A widespread screening with prostate-specific antigen (PSA) has led increased diagnosis of localized prostate cancer along with a reduction in the proportion of advanced-stage disease at diagnosis. Over the past decade, interest in focal therapy as a less morbid option for the treatment of localized low-risk prostate cancer has recently been renewed due to downward stage migration. Focal therapy stands midway between active surveillance and radical treatments, combining minimal morbidity with...

  16. Enrichment of prostate cancer stem cells from primary prostate cancer cultures of biopsy samples

    Wang, Shunqi; Huang, Shengsong; Zhao, Xin; Zhang, Qimin; Wu, Min; Sun, Feng; Han, Gang; Wu, Denglong

    2013-01-01

    This study was to enrich prostate cancer stem cells (PrCSC) from primary prostate cancer cultures (PPrCC). Primary prostate cancer cells were amplified in keratinocyte serum-free medium with epidermal growth factor (EGF) and bovine pituitary extract (BPE), supplemented with leukemia inhibitory factor (LIF), stem cell factor (SCF) and cholera toxin. After amplification, cells were transferred into ultra-low attachment dishes with serum-free DMEM/F12 medium, supplemented with EGF, basic fibrobl...

  17. Transmembrane prostatic acid phosphatase (TMPAP interacts with snapin and deficient mice develop prostate adenocarcinoma.

    Ileana B Quintero

    Full Text Available The molecular mechanisms underlying prostate carcinogenesis are poorly understood. Prostatic acid phosphatase (PAP, a prostatic epithelial secretion marker, has been linked to prostate cancer since the 1930's. However, the contribution of PAP to the disease remains controversial. We have previously cloned and described two isoforms of this protein, a secretory (sPAP and a transmembrane type-I (TMPAP. The goal in this work was to understand the physiological function of TMPAP in the prostate. We conducted histological, ultra-structural and genome-wide analyses of the prostate of our PAP-deficient mouse model (PAP(-/- with C57BL/6J background. The PAP(-/- mouse prostate showed the development of slow-growing non-metastatic prostate adenocarcinoma. In order to find out the mechanism behind, we identified PAP-interacting proteins byyeast two-hybrid assays and a clear result was obtained for the interaction of PAP with snapin, a SNARE-associated protein which binds Snap25 facilitating the vesicular membrane fusion process. We confirmed this interaction by co-localization studies in TMPAP-transfected LNCaP cells (TMPAP/LNCaP cells and in vivo FRET analyses in transient transfected LNCaP cells. The differential gene expression analyses revealed the dysregulation of the same genes known to be related to synaptic vesicular traffic. Both TMPAP and snapin were detected in isolated exosomes. Our results suggest that TMPAP is involved in endo-/exocytosis and disturbed vesicular traffic is a hallmark of prostate adenocarcinoma.

  18. 5alpha-reductase inhibitors in benign prostatic hyperplasia and prostate cancer risk reduction.

    Rittmaster, Roger S

    2008-04-01

    Androgens play an essential role in prostatic development and function, but are also involved in prostate disease pathogenesis. The primary prostatic androgen, dihydrotestosterone (DHT), is synthesized from testosterone by 5alpha-reductase types 1 and 2. Inhibition of the 5alpha-reductase isoenzymes therefore has potential therapeutic benefit in prostate disease. The two currently approved 5alpha-reductase inhibitors (5ARIs), finasteride and dutasteride, have demonstrated long-term efficacy and safety in the treatment of benign prostatic hyperplasia. Finasteride, a type-2 5ARI, has also been studied for its ability to reduce the incidence of biopsy-detectable prostate cancer in the Prostate Cancer Prevention Trial. Treatment with dutasteride, a dual 5ARI, has been shown to result in a greater degree and consistency of DHT suppression compared with finasteride. Two large-scale studies of dutasteride are currently investigating the role of near-maximal DHT suppression in the settings of prostate cancer risk reduction and expectant management of localized prostate cancer. PMID:18471794

  19. Holmium Laser enucleation of the prostate (HoLEP versus Transurethral Resection of the Prostate (TURP

    Luís Eduardo Durães Barboza

    2015-06-01

    Full Text Available OBJECTIVE:to evaluate the effectiveness and applicability of Holmium laser enucleation of the prostate (HoLEP - in the treatment of benign prostatic hyperplasia (BPH - in comparison to transurethral resection of the prostate (TURP.METHODS:patients with symptomatic prostatic hyperplasia and candidates for surgical treatment were selected. Both procedures were explained and they had choosen HoLEP or TURP. At the hospital were collected: age, date of birth, international prostate symptom score, urinary peak flow rate, prostate volume, post-voiding residual urine, globular volume and serum PSA. At the procedure operating time, morcellating time (HoLEP, bladder mucosal injury and intercurrences were collected. At the first postoperative day, globular volume and sodium. Besides that were observed the catheter indwelling time and hospital stay and after 90 days, urinary peak flow rate and international prostate symptom score. Statistical analisys have been done partially by Sinpe(r and also by a professional team.RESULTS:twenty patients in HoLEP group and 21 at TURP were operated. Baseline urinary peak flow rate was 8 ml/s in both groups and preoperative international prostate symptom score was 22 in HoLEP and 20 in TURP, very similar. Operative time was 85 minutes in HoLEP and 60 in TURP, pCONCLUSION:HoLEP is a feasible technique and is as effective as TURP on symptomatic prostatic hyperplasia surgical treatment.

  20. Is prostate cancer screening responsible for the negative results of prostate cancer treatment trials?

    Prasad, Vinay

    2016-08-01

    Clinical guidelines continue to move away from routine prostate specific antigen screening (PSA), once a widespread medical practice. A curious difference exists between early prostate cancer and early breast cancer. While randomized trials of therapy in early breast cancer continue to show overall survival benefit, this is not the case in prostate cancer, where prostatectomy was no better than observation in a recent trial, and where early androgen deprivation is no better than late androgen deprivation. Here, I make the case that prostate cancer screening contributes so greatly to over diagnosis that even treatment trials yield null results due to contamination with non-life threatening disease. PMID:27372859

  1. Multiparametric magnetic resonance imaging of prostate cancer

    Sandeep S Hedgire

    2012-01-01

    Full Text Available In India, prostate cancer has an incidence rate of 3.9 per 100,000 men and is responsible for 9% of cancer-related mortality. It is the only malignancy that is diagnosed with an apparently blind technique, i.e., transrectal sextant biopsy. With increasing numbers of high-Tesla magnetic resonance imaging (MRI equipment being installed in India, the radiologist needs to be cognizant about endorectal MRI and multiparametric imaging for prostate cancer. In this review article, we aim to highlight the utility of multiparamteric MRI in prostate cancer. It plays a crucial role, mainly in initial staging, restaging, and post-treatment follow-up.

  2. AB271. Sexual dysfunction in chronic prostatitis

    Cho, In-Rae

    2016-01-01

    Chronic prostatitis/ chronic pelvic pain syndrome (CP/CPPS), or NIH category III prostatitis, is a clinical syndrome characterized by genital/ pelvic pain and lower urinary tract symptoms in the absence of urinary tract infection. CPPS is the most common prostatic disease in men younger than 50 years of age and the third most common in men older than 50 years of age. CP/CPPS is a complex entity with unclear etiology. Many articles reported that the high percentage of patients with CP/CPPS had...

  3. SATURATION BIOPSY OF THE PROSTATE (REVIEW

    A. V. Sadchenko

    2014-07-01

    Full Text Available Prostate biopsy is the principal method of diagnois of prostate cancer, allowing to start the adequate treatment. The tactics of the patients, which have negative initial biopsy, is a subject of discussion. Saturation biopsy is a “gold standard„ of diagnostics of PCA with repeat biopsy. Saturation biopsy of the prostate is not a primary procedure, usually apply in patients with negative biopsies in anamnesis, patients with multifocal PIN and ASAP. Saturation biopsy allows to more precisely predict the volume and degree of malignancy of PCA, that can be used for planning tactics of active surveillance and focal therapy.

  4. Transperineal percutaneous I-125 implant of prostate

    Although iodine-125 seeds for interstitial radiation of prostatic cancer via the retropubic route is an established method of treatment, the retropubic implant technique has disadvantages: inadequate space for proper placement of the needles, possible bleeding from the prostatic venous plexus by the insertion of needles through these veins, and possible wound infection due to inadvertent puncturing of the bladder and/or rectum by the needles. A technique is described whereby Iodine-125 seeds for interstitial radiation are placed into the prostate through the perineum allowing more accurate placement of the seeds, assuring homogenous dose distribution, and decreasing the risk of bleeding and of bacterial contamination

  5. Transperineal percutaneous I-125 implant of prostate

    Kumar, P.P.; Bartone, F.F.

    1981-03-01

    Although iodine-125 seeds for interstitial radiation of prostatic cancer via the retropubic route is an established method of treatment, the retropubic implant technique has disadvantages: inadequate space for proper placement of the needles, possible bleeding from the prostatic venous plexus by the insertion of needles through these veins, and possible wound infection due to inadvertent puncturing of the bladder and/or rectum by the needles. A technique is described whereby Iodine-125 seeds for interstitial radiation are placed into the prostate through the perineum allowing more accurate placement of the seeds, assuring homogenous dose distribution, and decreasing the risk of bleeding and of bacterial contamination.

  6. Obesity, body composition, and prostate cancer

    Fowke Jay H

    2012-01-01

    Full Text Available Abstract Background Established risk factors for prostate cancer have not translated to effective prevention or adjuvant care strategies. Several epidemiologic studies suggest greater body adiposity may be a modifiable risk factor for high-grade (Gleason 7, Gleason 8-10 prostate cancer and prostate cancer mortality. However, BMI only approximates body adiposity, and may be confounded by centralized fat deposition or lean body mass in older men. Our objective was to use bioelectric impedance analysis (BIA to measure body composition and determine the association between prostate cancer and total body fat mass (FM fat-free mass (FFM, and percent body fat (%BF, and which body composition measure mediated the association between BMI or waist circumference (WC with prostate cancer. Methods The study used a multi-centered recruitment protocol targeting men scheduled for prostate biopsy. Men without prostate cancer at biopsy served as controls (n = 1057. Prostate cancer cases were classified as having Gleason 6 (n = 402, Gleason 7 (n = 272, or Gleason 8-10 (n = 135 cancer. BIA and body size measures were ascertained by trained staff prior to diagnosis, and clinical and comorbidity status were determined by chart review. Analyses utilized multivariable linear and logistic regression. Results Body size and composition measures were not significantly associated with low-grade (Gleason 6 prostate cancer. In contrast, BMI, WC, FM, and FFM were associated with an increased risk of Gleason 7 and Gleason 8-10 prostate cancer. Furthermore, BMI and WC were no longer associated with Gleason 8-10 (ORBMI = 1.039 (1.000, 1.081, ORWC = 1.016 (0.999, 1.033, continuous scales with control for total body FFM (ORBMI = 0.998 (0.946, 1.052, ORWC = 0.995 (0.974, 1.017. Furthermore, increasing FFM remained significantly associated with Gleason 7 (ORFFM = 1.030 (1.008, 1.052 and Gleason 8-10 (ORFFM = 1.044 (1.014, 1.074 after controlling for FM. Conclusions Our results

  7. Novel diagnostic biomarkers for prostate cancer

    Chikezie O. Madu, Yi Lu

    2010-01-01

    Full Text Available Prostate cancer is the most frequently diagnosed malignancy in American men, and a more aggressive form of the disease is particularly prevalent among African Americans. The therapeutic success rate for prostate cancer can be tremendously improved if the disease is diagnosed early. Thus, a successful therapy for this disease depends heavily on the clinical indicators (biomarkers for early detection of the presence and progression of the disease, as well as the prediction after the clinical intervention. However, the current clinical biomarkers for prostate cancer are not ideal as there remains a lack of reliable biomarkers that can specifically distinguish between those patients who should be treated adequately to stop the aggressive form of the disease and those who should avoid overtreatment of the indolent form.A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. A biomarker reveals further information to presently existing clinical and pathological analysis. It facilitates screening and detecting the cancer, monitoring the progression of the disease, and predicting the prognosis and survival after clinical intervention. A biomarker can also be used to evaluate the process of drug development, and, optimally, to improve the efficacy and safety of cancer treatment by enabling physicians to tailor treatment for individual patients. The form of the prostate cancer biomarkers can vary from metabolites and chemical products present in body fluid to genes and proteins in the prostate tissues.Current advances in molecular techniques have provided new tools facilitating the discovery of new biomarkers for prostate cancer. These emerging biomarkers will be beneficial and critical in developing new and clinically reliable indicators that will have a high specificity for the diagnosis and prognosis of

  8. Diabetes and Risk of Prostate Cancer

    Tseng, Chin-Hsiao

    2011-01-01

    OBJECTIVE The link between diabetes and prostate cancer is rarely studied in Asians. RESEARCH DESIGN AND METHODS The trend of age-standardized prostate cancer incidence in 1995–2006 in the Taiwanese general population was calculated. A random sample of 1,000,000 subjects covered by the National Health Insurance in 2005 was recruited. A total of 494,630 men for all ages and 204,741 men ≥40 years old and without prostate cancer at the beginning of 2003 were followed to the end of 2005. Cumulati...

  9. Ultrasonographic and cytopathologic aspects of prostate disease in 52 dogs

    Antonio Carlos Cunha Lacreta Junior

    2012-03-01

    Full Text Available This study evaluated 52 dogs, which were male, intact, varied in age, of pure or mixed breed, with clinical signs suggestive of prostatic disease. Each individual underwent an ultrasound examination and fine-needle aspiration biopsy of the prostate gland for cytological evaluation. Benign prostatic hyperplasia (BPH was the most frequent prostatic disease, followed by cystic benign prostatic hyperplasia, bacterial prostatitis, abscesses, cysts, adenocarcinoma, nonbacterial prostatitis and paraprostatic cysts. The highest frequencies of prostate disorder were found in mixed breeds, followed by poodles and German shepherds. Ultrasound examination allowed the determination of prostate size, as well as the visualization of the diseases affecting the gland, and was effective in guiding aspiration biopsy. The cytological evaluation of the gland, especially when associated with changes in ultrasound images, revealed the presumptive diagnosis of the condition.

  10. The novel prostate cancer antigen 3 (PCA3 biomarker

    Andreas Bourdoumis

    2010-12-01

    Full Text Available PCA3 is a prostate specific, nonprotein coding RNA that is significantly over expressed in prostate cancer, without any correlation to prostatic volume and/or other prostatic diseases (e.g. prostatitis. It can now easily be measured in urine with a novel transcription-mediated amplification based test. Quantification of PCA3 mRNA levels can predict the outcome of prostatic biopsies with a higher specificity rate in comparison to PSA. Several studies have demonstrated that PCA3 can be used as a prognostic marker of prostate cancer, especially in conjunction with other predictive markers. Novel PCA3-based nomograms have already been introduced into clinical practice. PCA3 test may be of valuable help in several PSA quandary situations such as negative prostatic biopsies, concomitant prostatic diseases, and active surveillance. Results from relevant clinical studies, comparative with PSA, are warranted in order to confirm the perspective of PCA3 to substitute PSA.

  11. Computed tomography in the evaluation of the suspected carcinomatous prostate

    Twenty-six patients with physical findings suspicious for prostatic cancer were examined by contrast-enhanced computed tomography (CT) of the prostate region prior to prostatic biopsy or resection. Twelve had benign hypertrophy and/or prostatitis and fourteen had adenocarcinoma. Prostatic contour, density, seminal vesicle 'angle,' extraprostatic soft tissue 'mass,' and the pelvic fat planes were evaluated. A nodular prostatic contour was found only in patients with adenocarcinoma of the prostate, indicating a role for CT in the diagnosis of this disease. Two patients with benign prostatic disease had extraprostatic soft tissue 'masses' identical to those seen in six patients with adenocarcinoma of the prostate, suggesting limited usefulness of CT in staging patients with known tumor. (orig.)

  12. Can Western Based Online Prostate Cancer Risk Calculators Be Used to Predict Prostate Cancer after Prostate Biopsy for the Korean Population?

    Lee, Dong Hoon; Jung, Ha Bum; Park, Jae Won; Kim, Kyu Hyun; Kim, Jongchan; Lee, Seung Hwan; Chung, Byung Ha

    2013-01-01

    Purpose To access the predictive value of the European Randomized Screening of Prostate Cancer Risk Calculator (ERSPC-RC) and the Prostate Cancer Prevention Trial Risk Calculator (PCPT-RC) in the Korean population. Materials and Methods We retrospectively analyzed the data of 517 men who underwent transrectal ultrasound guided prostate biopsy between January 2008 and November 2010. Simple and multiple logistic regression analysis were performed to compare the result of prostate biopsy. Area u...

  13. A nomogram based on age, prostate-specific antigen level, prostate volume and digital rectal examination for predicting risk of prostate cancer

    Tang, Ping; CHEN, HUI; Uhlman, Matthew; Lin, Yu-Rong; Deng, Xiang-Rong; Wang, Bin; Yang, Wen-Jun; Xie, Ke-Ji

    2012-01-01

    Nomograms for predicting the risk of prostate cancer developed using other populations may introduce sizable bias when applied to a Chinese cohort. In the present study, we sought to develop a nomogram for predicting the probability of a positive initial prostate biopsy in a Chinese population. A total of 535 Chinese men who underwent a prostatic biopsy for the detection of prostate cancer in the past decade with complete biopsy data were included. Stepwise logistic regression was used to det...

  14. IL-8 secretion in primary cultures of prostate cells is associated with prostate cancer aggressiveness

    Neveu B

    2014-05-01

    Full Text Available Bertrand Neveu*, Xavier Moreel*, Marie-Pier Deschênes-Rompré, Alain Bergeron, Hélène LaRue, Cherifa Ayari, Yves Fradet, Vincent FradetDepartment of Surgery, Laval University Cancer Research Centre, CHU de Quebec Research Centre, Quebec, QC, Canada *These authors contributed equally to this workBackground: Chronic inflammation is believed to be a major factor in prostate cancer initiation and promotion and has been studied using prostate cancer cells and immortalized cell lines. However, little is known about the contribution of normal cells to the prostatic microenvironment and inflammation. We aim to study the contribution of normal prostate epithelial cells to prostate inflammation and to link the inflammatory status of normal cells to prostate cancer aggressiveness.Materials and methods: Short-term primary cell cultures of normal epithelial prostate cells were derived from prostate biopsies from 25 men undergoing radical prostatectomy, cystoprostatectomy, or organ donation. Cells were treated with polyinosinic:polycytidylic acid, a mimic of double-stranded viral RNA and a potent inducer of the inflammatory response. Secretion of interleukin (IL-8 in the cell culture medium by untreated and treated cells was measured and we determined the association between IL-8 levels in these primary cell cultures and prostate cancer characteristics. The Fligner–Policello test was used to compare the groups.Results: Baseline and induced IL-8 secretion were highly variable between cultured cells from different patients. This variation was not related to drug use, past medical history, age, or preoperative prostate-specific antigen value. Nonetheless, an elevated secretion of IL-8 from normal cultured epithelial cells was associated with prostate cancer aggressiveness (P=0.0005.Conclusion: The baseline secretion of IL-8 from normal prostate epithelial cells in culture is strongly correlated with cancer aggressiveness and may drive prostate cancer

  15. Radiation-Induced Leiomyosarcoma of the Prostate after Brachytherapy for Prostatic Adenocarcinoma

    Hiroto Horiguchi

    2014-08-01

    Full Text Available Radiation therapy (RTx has been employed as a curative therapy for prostatic adenocarcinoma. RTx-induced sarcomas (RISs are rare, late adverse events, representing less than 0.2% of all irradiated patients. RISs are more aggressive tumors than prostatic adenocarcinomas. Herein, we present a case with RTx-induced prostatic leiomyosarcoma after permanent brachytherapy for prostatic adenocarcinoma. A 69-year-old male presented with dysuria and gross hematuria. Six years previously, he had been diagnosed with localized prostate cancer and was treated by permanent brachytherapy. Urethroscopy showed stenosis by a tumor at the prostate. Transurethral prostatectomy was performed for a diagnosis. Based on pathological findings, the diagnosis was leiomyosarcoma of the prostate. He was treated with three cycles of neoadjuvant chemotherapy (CTx that consisted of doxorubicin and ifosfamide (AI, followed by a prostatocystectomy with intrapelvic lymphadenectomy. The tumor extended from the prostate and infiltrated the bladder wall and serosa with lymphatic and venous invasion. The surgical margin was negative, and no residual prostatic adenocarcinoma was observed. The proportion of necrotic tumor cells by neoadjuvant CTx was around 50%. Subsequently, adjuvant CTx was offered, but the patient chose a follow-up without CTx. Local recurrence and lung metastasis were detected by computed tomography 3 months after the surgery. He was treated again with AI. However, CTx was not effective and he died 6 months after the operation. In conclusion, an effective treatment strategy for prostatic sarcoma should be developed in the near future, although the clinical feature of prostatic sarcoma remains unclear due to its rare incidence.

  16. Finasteride concentrations and prostate cancer risk: results from the Prostate Cancer Prevention Trial.

    Cindy H Chau

    Full Text Available In the Prostate Cancer Prevention Trial (PCPT, finasteride reduced the risk of prostate cancer by 25%, even though high-grade prostate cancer was more common in the finasteride group. However, it remains to be determined whether finasteride concentrations may affect prostate cancer risk. In this study, we examined the association between serum finasteride concentrations and the risk of prostate cancer in the treatment arm of the PCPT and determined factors involved in modifying drug concentrations.Data for this nested case-control study are from the PCPT. Cases were drawn from men with biopsy-proven prostate cancer and matched controls. Finasteride concentrations were measured using a liquid chromatography-mass spectrometry validated assay. The association of serum finasteride concentrations with prostate cancer risk was determined by logistic regression. We also examine whether polymorphisms in the enzyme target and metabolism genes of finasteride are related to drug concentrations using linear regression.Among men with detectable finasteride concentrations, there was no association between finasteride concentrations and prostate cancer risk, low-grade or high-grade, when finasteride concentration was analyzed as a continuous variable or categorized by cutoff points. Since there was no concentration-dependent effect on prostate cancer, any exposure to finasteride intake may reduce prostate cancer risk. Of the twenty-seven SNPs assessed in the enzyme target and metabolism pathway, five SNPs in two genes, CYP3A4 (rs2242480; rs4646437; rs4986910, and CYP3A5 (rs15524; rs776746 were significantly associated with modifying finasteride concentrations. These results suggest that finasteride exposure may reduce prostate cancer risk and finasteride concentrations are affected by genetic variations in genes responsible for altering its metabolism pathway.ClinicalTrials.gov NCT00288106.

  17. Road to Recovery from Prostate Cancer

    Full Text Available ... to make your dissection. I think the easiest secret to this is to have a 15 cc ... and lifting up the prostate is really the secret to getting into this right plane. My left ...

  18. Road to Recovery from Prostate Cancer

    Full Text Available ... fingers in order to develop this plane. The border of the resection is the vas deferens, which ... come down and clearly you can see the borders of the bladder with the prostate. If in ...

  19. Road to Recovery from Prostate Cancer

    Full Text Available ... 2008, while prostate cancer remains a very controversial subject, it is obviously a very important disease. It’s ... another question, which is a little off the subject concerning bladder cancer, so I’m actually going ...

  20. Road to Recovery from Prostate Cancer

    Full Text Available ... too enamored with the gimmick of using the robot or having limited bleeding and we’ve had ... the Department of Urology, I felt that the robot surgery for the treatment of prostate cancer is ...