Sample records for 1-integrin reverts prostate

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

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


    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

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


    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.

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

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


    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......-null phenotype in vivo. Surprisingly, neither the substitution of the tyrosines with phenylalanine nor the aspartic acid with alanine resulted in an obvious defect. These data suggest that the NPXY motifs of the beta1 integrin tail are essential for beta1 integrin function, whereas tyrosine phosphorylation......Akey feature of integrins is their ability to regulate the affinity for ligands, a process termed integrin activation. The final step in integrin activation is talin binding to the NPXY motif of the integrin beta cytoplasmic domains. Talin binding disrupts the salt bridge between the alpha/beta...

  5. Revertant mosaicism in the skin. (United States)

    Lai-Cheong, J E; McGrath, J A


    Revertant mosaicism is a naturally occurring phenomenon involving the spontaneous correction of a pathogenic mutation in a somatic cell. Revertant mosaicism is not a rare event and has been described in several inherited skin conditions, including various subtypes of epidermolysis bullosa. The recognition of revertant mosaicism paves the way for revertant therapy which represents a potentially exciting "natural gene therapy" option for genetic disorders. The skin provides a useful model for studying revertant mosaicism because it is readily accessible and easy to examine. In this paper, we provide an overview of revertant mosaicism and its relevance in genetic skin disorders.

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

    DEFF Research Database (Denmark)

    Bloch, W; Forsberg, E; Lentini, S


    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 ...... embryoid bodies. Moreover, while vascular endothelial growth factor induced proliferation of endothelial cells as well as an extensive branching of blood vessels in normal embryoid bodies, it had no effect in beta 1-null embryoid bodies....

  7. Reciprocal interactions between Beta1-integrin and epidermal growth factor in three-dimensional basement membrane breast cultures: A different perspective in epithelial biology

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    Wang, F.; Weaver, V.M.; Petersen, O.W.; Larabell, C.A.; Dedhar, S.; Briand, P.; Lupu, R.; Bissell, M.J.


    Anchorage and growth factor independence are cardinal features of the transformed phenotype. Although it is logical that the two pathways must be coregulated in normal tissues to maintain homeostasis, this has not been demonstrated directly. We showed previously that down-modulation of {beta}1-integrin signaling reverted the malignant behavior of a human breast tumor cell line (T4-2) derived from phenotypically normal cells (HMT-3522) and led to growth arrest in a threedimensional (3D) basement membrane assay in which the cells formed tissue-like acini (14). Here, we show that there is a bidirectional cross-modulation of {beta}1-integrin and epidermal growth factor receptor (EGFR) signaling via the mitogenactivated protein kinase (MAPK) pathway. The reciprocal modulation does not occur in monolayer (2D) cultures. Antibodymediated inhibition of either of these receptors in the tumor cells, or inhibition of MAPK kinase, induced a concomitant downregulation of both receptors, followed by growth-arrest and restoration of normal breast tissue morphogenesis. Crossmodulation and tissue morphogenesis were associated with attenuation of EGF-induced transient MAPK activation. To specifically test EGFR and {beta}1-integrin interdependency, EGFR was overexpressed in nonmalignant cells, leading to disruption of morphogenesis and a compensatory up-regulation of {beta}1-integrin expression, again only in 3D. Our results indicate that when breast cells are spatially organized as a result of contact with basement membrane, the signaling pathways become coupled and bidirectional. They further explain why breast cells fail to differentiate in monolayer cultures in which these events are mostly uncoupled. Moreover, in a subset of tumor cells in which these pathways are misregulated but functional, the cells could be 'normalized' by manipulating either pathway.

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

    DEFF Research Database (Denmark)

    Brakebusch, C; Wennerberg, K; Krell, H W


    , tumors induced by the high expressing clones 1A10 and 2F2 were markedly smaller, suggesting an inverse correlation of tumor growth and beta1 integrin expression. The metastasis potential of all three beta1 integrin-expressing GERM 11 sublines tested was significantly higher than that of the beta1......To investigate the role of beta1 integrin during tumor metastasis, we established a ras-myc transformed fibroblastoid cell line with a disrupted beta1 integrin gene on both alleles (GERM 11). Stable transfection of this cell line with an expression vector encoding beta1A integrin resulted in beta1A...... 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...

  9. Prostatitis


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


    The laboratory diagnosis of acute bacterial prostatitis is straightforward and easily accomplished in clinical laboratories. Chronic bacterial prostatitis, and especially chronic idiopathic prostatitis (most often referred to as abacterial prostatitis), presents a real challenge to the clinician and clinical microbiologist. Clinically, the diagnosis of chronic idiopathic prostatitis is differentiated from that of acute prostatitis by a lack of prostatic inflammation and no “significant” (cont...

  10. β1 integrin-mediated signals are required for platelet granule secretion and hemostasis in mouse. (United States)

    Petzold, Tobias; Ruppert, Raphael; Pandey, Dharmendra; Barocke, Verena; Meyer, Hannelore; Lorenz, Michael; Zhang, Lin; Siess, Wolfgang; Massberg, Steffen; Moser, Markus


    Integrins are critical for platelet adhesion and aggregation during arterial thrombosis and hemostasis. Although the platelet-specific αIIbβ3 integrin is known to be crucial for these processes, the in vivo role of β1 integrins is a matter of debate. Here we demonstrate that mice expressing reduced levels of β1 integrins or an activation-deficient β1 integrin show strongly reduced platelet adhesion to collagen in vitro and in a carotis ligation model in vivo. Interestingly, hypomorphic mice expressing only 3% of β1 integrins on platelets show normal bleeding times despite reduced platelet adhesion. The residual 3% of β1 integrins are able to trigger intracellular signals driving Rac-1-dependent granule release required for platelet aggregation and hemostasis. Our findings support a model, in which platelet β1 integrins serve as an important signaling receptor rather than an adhesion receptor in vivo and therefore promote β1 integrins as a promising and so far clinically unemployed antithrombotic target.

  11. CCM proteins control endothelial β1 integrin dependent response to shear stress

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    Zuzana Macek Jilkova


    Full Text Available Hemodynamic shear stress from blood flow on the endothelium critically regulates vascular function in many physiological and pathological situations. Endothelial cells adapt to shear stress by remodeling their cytoskeletal components and subsequently by changing their shape and orientation. We demonstrate that β1 integrin activation is critically controlled during the mechanoresponse of endothelial cells to shear stress. Indeed, we show that overexpression of the CCM complex, an inhibitor of β1 integrin activation, blocks endothelial actin rearrangement and cell reorientation in response to shear stress similarly to β1 integrin silencing. Conversely, depletion of CCM2 protein leads to an elongated “shear-stress-like” phenotype even in the absence of flow. Taken together, our findings reveal the existence of a balance between positive extracellular and negative intracellular signals, i.e. shear stress and CCM complex, for the control of β1 integrin activation and subsequent adaptation of vascular endothelial cells to mechanostimulation by fluid shear stress.

  12. Expression of {beta}{sub 1} integrins in human endometrial stromal and decidual cells

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    Shiokawa, Shigetatsu; Yoshimura, Yasunori; Nakamura, Yukio [Kyorin Univ. School of Medicine, Tokyo (Japan)] [and others


    The present study was undertaken to investigate the expression of {beta}{sub 1} integrins in human endometrium and decidua using flow cytometry, immunohistochemistry, and immunoprecipitation. Fluorescence-activated flow cytometry demonstrated the greater expression of the {beta}{sub 1}, {alpha}{sub 1}, {alpha}{sub 2}, and {alpha}{sub 5} subunits of the {beta}{sub 1} integrin family in cultured stromal cells from the midsecretory phase, than in those of the early proliferative phase. The addition of estradiol (E{sub 2}) and progesterone (P) to cultured stromal cells in the early proliferative phase increased the expression of {beta}{sub 1} integrins in vitro. Flow cytometry also demonstrated the expression of the {beta}{sub 1}, {alpha}{sub 1}, {alpha}{sub 2}, {alpha}{sub 3}, {alpha}{sub 5}, and {alpha}{sub 6} subunits of {beta}{sub 1} integrin family in cultured decidual cells, and the enriched-fraction of prolactin (PRL)-producing decidual cells isolated by Percoll gradients showed high levels of {beta}{sub 1} integrins expression. Immunohistochemistry confirmed the {beta}{sub 1} integrin cell surface phenotypes in cultured decidual cells observed by flow cytometry. In summary, the present study demonstrated that endometrial stromal and decidual cells expressed {beta}{sub 1} integrin subunits at their surfaces. The expression exhibited a variability throughout the menstrual cycles, being predominantly detected in the secretory phase, and was maintained highly in the decidua. Thus, {beta}{sub 1} integrins in human endometrium and decidua may be important in mediating the organization of extracellular matrix proteins derived from embryos during the early stage of implantation. 43 refs., 7 figs., 2 tabs.

  13. Neisseria meningitidis adhesin NadA targets beta1 integrins: functional similarity to Yersinia invasin. (United States)

    Nägele, Virginie; Heesemann, Jürgen; Schielke, Stephanie; Jiménez-Soto, Luisa F; Kurzai, Oliver; Ackermann, Nikolaus


    Meningococci are facultative-pathogenic bacteria endowed with a set of adhesins allowing colonization of the human upper respiratory tract, leading to fulminant meningitis and septicemia. The Neisseria adhesin NadA was identified in about 50% of N. meningitidis isolates and is closely related to the Yersinia adhesin YadA, the prototype of the oligomeric coiled-coil adhesin (Oca) family. NadA is known to be involved in cell adhesion, invasion, and induction of proinflammatory cytokines. Because of the enormous diversity of neisserial cell adhesins the analysis of the specific contribution of NadA in meningococcal host interactions is limited. Therefore, we used a non-invasive Y. enterocolitica mutant as carrier to study the role of NadA in host cell interaction. NadA was shown to be efficiently produced and localized in its oligomeric form on the bacterial surface of Y. enterocolitica. Additionally, NadA mediated a β1 integrin-dependent adherence with subsequent internalization of yersiniae by a β1 integrin-positive cell line. Using recombinant NadA(24-210) protein and human and murine β1 integrin-expressing cell lines we could demonstrate the role of the β1 integrin subunit as putative receptor for NadA. Subsequent inhibition assays revealed specific interaction of NadA(24-210) with the human β1 integrin subunit. Cumulatively, these results indicate that Y. enterocolitica is a suitable toolbox system for analysis of the adhesive properties of NadA, revealing strong evidence that β1 integrins are important receptors for NadA. Thus, this study demonstrated for the first time a direct interaction between the Oca-family member NadA and human β1 integrins.

  14. Calpains promote α2β1 integrin turnover in nonrecycling integrin pathway. (United States)

    Rintanen, Nina; Karjalainen, Mikko; Alanko, Jonna; Paavolainen, Lassi; Mäki, Anita; Nissinen, Liisa; Lehkonen, Moona; Kallio, Katri; Cheng, R Holland; Upla, Paula; Ivaska, Johanna; Marjomäki, Varpu


    Collagen receptor integrins recycle between the plasma membrane and endosomes and facilitate formation and turnover of focal adhesions. In contrast, clustering of α2β1 integrin with antibodies or the human pathogen echovirus 1 (EV1) causes redistribution of α2 integrin to perinuclear multivesicular bodies, α2-MVBs. We show here that the internalized clustered α2 integrin remains in α2-MVBs and is not recycled back to the plasma membrane. Instead, receptor clustering and internalization lead to an accelerated down-regulation of α2β1 integrin compared to the slow turnover of unclustered α2 integrin. EV1 infection or integrin degradation is not associated with proteasomal or autophagosomal processes and shows no significant association with lysosomal pathway. In contrast, degradation is dependent on calpains, such that it is blocked by calpain inhibitors. We show that active calpain is present in α2-MVBs, internalized clustered α2β1 integrin coprecipitates with calpain-1, and calpain enzymes can degrade α2β1 integrin. In conclusion, we identified a novel virus- and clustering-specific pathway that diverts α2β1 integrin from its normal endo/exocytic traffic to a nonrecycling, calpain-dependent degradative endosomal route.

  15. RCP induces Slug expression and cancer cell invasion by stabilizing β1 integrin. (United States)

    Hwang, M H; Cho, K H; Jeong, K J; Park, Y-Y; Kim, J M; Yu, S-L; Park, C G; Mills, G B; Lee, H Y


    Rab coupling protein (RCP)-induced tumor cell migration has been implicated in tumor pathophysiology and patient outcomes. In the present study, we demonstrate that RCP stabilizes β1 integrin leading to increased β1 integrin levels and activation of a signaling cascade culminating in Slug induction, epithelial-to-mesenchymal transition and increased invasion. Ectopic expression of RCP induced Slug expression. Silencing β1 integrin efficiently inhibited RCP-induced Slug expression and subsequent cancer cell invasion. Conversely, ectopic expression of β1 integrin was sufficient to induce Slug expression. Pharmacological inhibition of integrin linked kinase (ILK), EGFR and NF-κB, as well as transfection of a dominant-negative mutant of Ras (RasN17), significantly inhibited RCP-induced Slug expression and cancer cell invasion. Strikingly, ectopic expression of RCP was sufficient to enhance metastasis of ovarian cancer cells to the lung. Collectively, we demonstrate a mechanism by which RCP promotes cancer cell aggressiveness through sequential β1 integrin stabilization, activation of an ILK/EGFR/Ras/NF-κB signaling cascade and subsequent Slug expression.

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

    DEFF Research Database (Denmark)

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


    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....

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

    DEFF Research Database (Denmark)

    Lafuste, Peggy; Sonnet, Corinne; Chazaud, Bénédicte;


    Knowledge on molecular systems involved in myogenic precursor cell (mpc) fusion into myotubes is fragmentary. Previous studies have implicated the a disintegrin and metalloproteinase (ADAM) family in most mammalian cell fusion processes. ADAM12 is likely involved in fusion of murine mpc and human...... rhabdomyosarcoma cells, but it requires yet unknown molecular partners to launch myogenic cell fusion. ADAM12 was shown able to mediate cell-to-cell attachment through binding alpha9beta1 integrin. We report that normal human mpc express both ADAM12 and alpha9beta1 integrin during their differentiation. Expression...... 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 fusion...

  18. Role of the beta1-integrin cytoplasmic tail in mediating invasin-promoted internalization of Yersinia

    DEFF Research Database (Denmark)

    Gustavsson, Anna; Armulik, Annika; Brakebusch, Cord


    Invasin of Yersinia pseudotuberculosis binds to beta1-integrins on host cells and triggers internalization of the bacterium. To elucidate the mechanism behind the beta1-integrin-mediated internalization of Yersinia, a beta1-integrin-deficient cell line, GD25, transfected with wild-type beta1A, beta......1B or different mutants of the beta1A subunit was used. Both beta1A and beta1B bound to invasin-expressing bacteria, but only beta1A was able to mediate internalization of the bacteria. The cytoplasmic region of beta1A, differing from beta1B, contains two NPXY motifs surrounding a double threonine...... site. Exchanging the tyrosines of the two NPXYs to phenylalanines did not inhibit the uptake, whereas a marked reduction was seen when the first tyrosine (Y783) was exchanged to alanine. A similar reduction was seen when the two nearby threonines (TT788-9) were exchanged with alanines. It was also...

  19. Regulation of neural progenitor proliferation and survival by beta1 integrins

    DEFF Research Database (Denmark)

    Leone, Dino P; Relvas, João B; Campos, Lia S;


    Neural stem cells give rise to undifferentiated nestin-positive progenitors that undergo extensive cell division before differentiating into neuronal and glial cells. The precise control of this process is likely to be, at least in part, controlled by instructive cues originating from...... the extracellular environment. Some of these cues are interpreted by the integrin family of extracellular matrix receptors. Using neurosphere cell cultures as a model system, we show that beta1-integrin signalling plays a crucial role in the regulation of progenitor cell proliferation, survival and migration....... Following conditional genetic ablation of the beta1-integrin allele, and consequent loss of beta1-integrin cell surface protein, mutant nestin-positive progenitor cells proliferate less and die in higher numbers than their wild-type counterparts. Mutant progenitor cell migration on different ECM substrates...

  20. Dominant Suppression of β1 Integrin by Ectopic CD98-ICD Inhibits Hepatocellular Carcinoma Progression

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    Bo Wu


    Full Text Available Hepatocellular carcinoma (HCC is currently the third most common cause of cancer-related death in the Asia-Pacific region. Our previous work showed that knockdown of CD98 significantly inhibits malignant HCC cell phenotypes in vitro and in vivo. The level of CD98 in the membrane is tightly regulated to mediate complex processes associated with cell–cell communication and intracellular signaling. In addition, the intracellular domain of CD98 (CD98-ICD seems to be of vital importance for recycling CD98 to the membrane after it is endocytosed. The intracellular and transmembrane domains of CD98 associate with β-integrins (primarily β1 but also β3, and this association is essential for CD98 mediation of integrin-like signaling and complements dominant suppression of β1-integrin. We speculated that isolated CD98-ICD would similarly suppress β1-integrin activation and inhibit the malignant behaviors of cancer cells. In particular, the exact role of CD98-ICD has not been studied independently in HCC. In this study, we found that ectopic expression of CD98-ICD inhibited the malignant phenotypes of HCC cells, and the mechanism possibly involves β1-integrin suppression. Moreover, the expression levels of CD98, β1-integrin-A (the activated form of β1-integrin and Ki-67 were significantly increased in HCC tissues relative to those of normal liver tissues. Therefore, our preliminary study indicates that ectopic CD98-ICD has an inhibitory role in the malignant development of HCC, and shows that CD98-ICD acts as a dominant negative mutant of CD98 that attenuates β1-integrin activation. CD98-ICD may emerge as a promising candidate for antitumor treatment.

  1. Revertant mosaicism in human genetic disorders

    NARCIS (Netherlands)

    Jonkman, MF


    Somatic reversion of inherited mutations is known for many years in plant breeding, however it was recognized only recently in humans. The concept of revertant mosaicism is important in medical genetics. (C) 1999 Wiley-Liss, Inc.

  2. [Revertant somatic mosaicism in primary immunodeficiency diseases]. (United States)

    Wada, Taizo


    Revertant somatic mosaicism has been described in an increasing number of genetic disorders including primary immunodeficiency diseases. Both back mutations leading to restoration of wild-type sequences and second-site mutations resulting in compensatory changes have been demonstrated in mosaic individuals. Recent studies identifying revertant somatic mosaicism caused by multiple independent genetic changes further support its frequent occurrence in primary immunodeficiency diseases. Revertant mosaicism acquires a particular clinical relevance because it may lead to selective growth advantage of the corrected cells, resulting in improvement of disease symptoms or atypical clinical presentations. This phenomenon also provides us unique opportunities to evaluate the biological effects of restored gene expression in different cell lineages. Here we review the recent findings of revertant somatic mosaicism in primary immunodeficiency diseases and discuss its clinical implications.

  3. beta1 integrins are not required for the maintenance of lymphocytes within intestinal epithelia

    DEFF Research Database (Denmark)

    Marsal, Jan; Brakebusch, Cord; Bungartz, Gerd;


    beta(1) integrins are thought to play a central role in maintaining lymphocytes within mucosal epithelia via their interactions with extracellular matrix proteins and subepithelial cellular components within and underlying the basement membrane. In the current study type a (CD8alphabeta...

  4. Human Parechovirus 1 Infection Occurs via αVβ1 Integrin. (United States)

    Merilahti, Pirjo; Tauriainen, Sisko; Susi, Petri


    Human parechovirus 1 (HPeV-1) (family Picornaviridae) is a global cause of pediatric respiratory and CNS infections for which there is no treatment. Although biochemical and in vitro studies have suggested that HPeV-1 binds to αVβ1, αVβ3 and αVβ6 integrin receptor(s), the actual cellular receptors required for infectious entry of HPeV-1 remain unknown. In this paper we analyzed the expression profiles of αVβ1, αVβ3, αVβ6 and α5β1 in susceptible cell lines (A549, HeLa and SW480) to identify which integrin receptors support HPeV-1 internalization and/or replication cycle. We demonstrate by antibody blocking assay, immunofluorescence microscopy and RT-qPCR that HPeV-1 internalizes and replicates in cell lines that express αVβ1 integrin but not αVβ3 or αVβ6 integrins. To further study the role of β1 integrin, we used a mouse cell line, GE11-KO, which is deficient in β1 expression, and its derivate GE11-β1 in which human integrin β1 subunit is overexpressed. HPeV-1 (Harris strain) and three clinical HPeV-1 isolates did not internalize into GE11-KO whereas GE11-β1 supported the internalization process. An integrin β1-activating antibody, TS2/16, enhanced HPeV-1 infectivity, but infection occurred in the absence of visible receptor clustering. HPeV-1 also co-localized with β1 integrin on the cell surface, and HPeV-1 and β1 integrin co-endocytosed into the cells. In conclusion, our results demonstrate that in some cell lines the cellular entry of HPeV-1 is primarily mediated by the active form of αVβ1 integrin without visible receptor clustering.

  5. Novel monoclonal antibody against beta 1 integrin enhances cisplatin efficacy in human lung adenocarcinoma cells. (United States)

    Kim, Min-Young; Cho, Woon-Dong; Hong, Kwon Pyo; Choi, Da Bin; Hong, Jeong Won; Kim, Soseul; Moon, Yoo Ri; Son, Seung-Myoung; Lee, Ok-Jun; Lee, Ho-Chang; Song, Hyung Geun


    The use of anti-beta 1 integrin monoclonal antibody in lung cancer treatment has proven beneficial. Here, we developed a novel monoclonal antibody (mAb), called P5, by immunizing mice with human peripheral blood mononuclear cells (PBMC). Its anti-tumor effect is now being tested, in a clinical phase III trial, in combinatorial treatments with various chemical drugs. To confirm that P5 indeed binds to beta 1 integrin, cell lysates were immunoprecipitated with commercial anti-beta 1 integrin mAb (TS2/16) and immunoblotted against P5 to reveal a 140 kDa molecular weight band, as expected. Immunoprecipitation with P5 followed by LC/MS protein sequence analysis further verified P5 antigen to be beta 1 integrin. Cisplatin treatment upregulated cell surface expression of beta 1 integrin in A549 cells, while causing inhibition of cell growth. When cells were co-treated with different concentrations of P5 mAb, the cisplatin-mediated inhibitory effect was enhanced in a dose-dependent manner. Our findings show that a combinatorial treatment of P5 mAb and cisplatin in A549 cells resulted in a 30% increase in apoptosis, compared to baseline, and significantly more when compared to either the cisplatin or P5 alone group. The entire peptide sequences in CDR from variable region of Ig heavy and light chain gene for P5 mAb are also disclosed. Together, these results provide evidence of the beneficial effect of P5 mAb in combinatorial treatment of human lung adenocarcinoma.

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

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    Carlstrom Lucas P


    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

  7. Ablation of beta1 integrin in mammary epithelium reveals a key role for integrin in glandular morphogenesis and differentiation. (United States)

    Naylor, Matthew J; Li, Na; Cheung, Julia; Lowe, Emma T; Lambert, Elise; Marlow, Rebecca; Wang, Pengbo; Schatzmann, Franziska; Wintermantel, Timothy; Schüetz, Günther; Clarke, Alan R; Mueller, Ulrich; Hynes, Nancy E; Streuli, Charles H


    Integrin-mediated adhesion regulates the development and function of a range of tissues; however, little is known about its role in glandular epithelium. To assess the contribution of beta1 integrin, we conditionally deleted its gene in luminal epithelia during different stages of mouse mammary gland development and in cultured primary mammary epithelia. Loss of beta1 integrin in vivo resulted in impaired alveologenesis and lactation. Cultured beta1 integrin-null cells displayed abnormal focal adhesion function and signal transduction and could not form or maintain polarized acini. In vivo, epithelial cells became detached from the extracellular matrix but remained associated with each other and did not undergo overt apoptosis. beta1 integrin-null mammary epithelial cells did not differentiate in response to prolactin stimulation because of defective Stat5 activation. In mice where beta1 integrin was deleted after the initiation of differentiation, fewer defects in alveolar morphology occurred, yet major deficiencies were also observed in milk protein and milk fat production and Stat5 activation, indicating a permissive role for beta1 integrins in prolactin signaling. This study demonstrates that beta1 integrin is critical for the alveolar morphogenesis of a glandular epithelium and for maintenance of its differentiated function. Moreover, it provides genetic evidence for the cooperation between integrin and cytokine signaling pathways.

  8. An essential requirement for β1 integrin in the assembly of extracellular matrix proteins within the vascular wall. (United States)

    Turlo, Kirsten A; Noel, Onika D V; Vora, Roshni; LaRussa, Marie; Fassler, Reinhard; Hall-Glenn, Faith; Iruela-Arispe, M Luisa


    β1 integrin has been shown to contribute to vascular smooth muscle cell differentiation, adhesion and mechanosensation in vitro. Here we showed that deletion of β1 integrin at the onset of smooth muscle differentiation resulted in interrupted aortic arch, aneurysms and failure to assemble extracellular matrix proteins. These defects result in lethality prior to birth. Our data indicates that β1 integrin is not required for the acquisition, but it is essential for the maintenance of the smooth muscle cell phenotype, as levels of critical smooth muscle proteins are gradually reduced in mutant mice. Furthermore, while deposition of extracellular matrix was not affected, its structure was disrupted. Interestingly, defects in extracellular matrix and vascular wall assembly, were restricted to the aortic arch and its branches, compromising the brachiocephalic and carotid arteries and to the exclusion of the descending aorta. Additional analysis of β1 integrin in the pharyngeal arch smooth muscle progenitors was performed using wnt1Cre. Neural crest cells deleted for β1 integrin were able to migrate to the pharyngeal arches and associate with endothelial lined arteries; but exhibited vascular remodeling defects and early lethality. This work demonstrates that β1 integrin is dispensable for migration and initiation of the smooth muscle differentiation program, however, it is essential for remodeling of the pharyngeal arch arteries and for the assembly of the vessel wall of their derivatives. It further establishes a critical role of β1 integrin in the protection against aneurysms that is particularly confined to the ascending aorta and its branches.

  9. Dystrophin Dp71f associates with the beta1-integrin adhesion complex to modulate PC12 cell adhesion. (United States)

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


    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 beta1-integrin in the cell area contacting the substrate. In this study, we isolated additional antisense-Dp71 clones to analyze in detail the potential involvement of Dp71f isoform with the beta1-integrin adhesion system of PC12 cells. Immunofluorescence analyses as well as immunoprecipitation assays demonstrated that the PC12 cell beta1-integrin adhesion complex is composed of beta1-integrin, talin, paxillin, alpha-actinin, FAK and actin. In addition, our results showed that Dp71f associates with most of the beta1-integrin complex components (beta1-integrin, FAK, alpha-actinin, talin and actin). In the antisense-Dp71 cells, the deficiency of Dp71 provokes a significant reduction of the beta1-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 beta1-integrin. Our data indicate that Dp71f is a structural component of the beta1-integrin adhesion complex of PC12 cells that modulates PC12 cell adhesion by conferring proper complex assembly and/or maintenance.

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

    DEFF Research Database (Denmark)

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


    Inhibiting the alpha(4) subunit of the integrin heterodimers alpha(4)beta(1) and alpha(4)beta(7) with the monoclonal antibody natalizumab is an effective treatment for multiple sclerosis (MS). However, the pharmacological action of natalizumab is not understood conclusively. Previous studies...... suggested that natalizumab inhibits activation, proliferation, or extravasation of inflammatory cells. To specify which mechanisms, cell types, and alpha(4) heterodimers are affected by the antibody treatment, we studied MS-like experimental autoimmune encephalomyelitis (EAE) in mice lacking the beta(1......)-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...

  11. Distinct roles for dystroglycan, beta1 integrin and perlecan in cell surface laminin organization

    DEFF Research Database (Denmark)

    Henry, M D; Satz, J S; Brakebusch, C;


    Dystroglycan (DG) is a cell surface receptor for several extracellular matrix (ECM) molecules including laminins, agrin and perlecan. Recent data indicate that DG function is required for the formation of basement membranes in early development and the organization of laminin on the cell surface....... Here we show that DG-mediated laminin clustering on mouse embryonic stem (ES) cells is a dynamic process in which clusters are consolidated over time into increasingly more complex structures. Utilizing various null-mutant ES cell lines, we define roles for other molecules in this process. In beta1...... integrin-deficient ES cells, laminin-1 binds to the cell surface, but fails to organize into more morphologically complex structures. This result indicates that beta1 integrin function is required after DG function in the cell surface-mediated laminin assembly process. In perlecan-deficient ES cells...

  12. Allosteric Modulation of Beta1 Integrin Function Induces Lung Tissue Repair

    Directory of Open Access Journals (Sweden)

    Rehab AlJamal-Naylor


    Full Text Available The cellular cytoskeleton, adhesion receptors, extracellular matrix composition, and their spatial distribution are together fundamental in a cell's balanced mechanical sensing of its environment. We show that, in lung injury, extracellular matrix-integrin interactions are altered and this leads to signalling alteration and mechanical missensing. The missensing, secondary to matrix alteration and cell surface receptor alterations, leads to increased cellular stiffness, injury, and death. We have identified a monoclonal antibody against β1 integrin which caused matrix remodelling and enhancement of cell survival. The antibody acts as an allosteric dual agonist/antagonist modulator of β1 integrin. Intriguingly, this antibody reversed both functional and structural tissue injury in an animal model of degenerative disease in lung.

  13. Electric Signals Regulate the Directional Migration of Oligodendrocyte Progenitor Cells (OPCs) via β1 Integrin. (United States)

    Zhu, Bangfu; Nicholls, Matthew; Gu, Yu; Zhang, Gaofeng; Zhao, Chao; Franklin, Robin J M; Song, Bing


    The guided migration of neural cells is essential for repair in the central nervous system (CNS). Oligodendrocyte progenitor cells (OPCs) will normally migrate towards an injury site to re-sheath demyelinated axons; however the mechanisms underlying this process are not well understood. Endogenous electric fields (EFs) are known to influence cell migration in vivo, and have been utilised in this study to direct the migration of OPCs isolated from neonatal Sprague-Dawley rats. The OPCs were exposed to physiological levels of electrical stimulation, and displayed a marked electrotactic response that was dependent on β1 integrin, one of the key subunits of integrin receptors. We also observed that F-actin, an important component of the cytoskeleton, was re-distributed towards the leading edge of the migrating cells, and that this asymmetric rearrangement was associated with β1 integrin function.

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

    Energy Technology Data Exchange (ETDEWEB)

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


    {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. β1 integrin signaling promotes neuronal migration along vascular scaffolds in the post-stroke brain

    Directory of Open Access Journals (Sweden)

    Teppei Fujioka


    Full Text Available Cerebral ischemic stroke is a main cause of chronic disability. However, there is currently no effective treatment to promote recovery from stroke-induced neurological symptoms. Recent studies suggest that after stroke, immature neurons, referred to as neuroblasts, generated in a neurogenic niche, the ventricular-subventricular zone, migrate toward the injured area, where they differentiate into mature neurons. Interventions that increase the number of neuroblasts distributed at and around the lesion facilitate neuronal repair in rodent models for ischemic stroke, suggesting that promoting neuroblast migration in the post-stroke brain could improve efficient neuronal regeneration. To move toward the lesion, neuroblasts form chain-like aggregates and migrate along blood vessels, which are thought to increase their migration efficiency. However, the molecular mechanisms regulating these migration processes are largely unknown. Here we studied the role of β1-class integrins, transmembrane receptors for extracellular matrix proteins, in these migrating neuroblasts. We found that the neuroblast chain formation and blood vessel-guided migration critically depend on β1 integrin signaling. β1 integrin facilitated the adhesion of neuroblasts to laminin and the efficient translocation of their soma during migration. Moreover, artificial laminin-containing scaffolds promoted neuroblast chain formation and migration toward the injured area. These data suggest that laminin signaling via β1 integrin supports vasculature-guided neuronal migration to efficiently supply neuroblasts to injured areas. This study also highlights the importance of vascular scaffolds for cell migration in development and regeneration.

  16. β1 integrin signaling promotes neuronal migration along vascular scaffolds in the post-stroke brain. (United States)

    Fujioka, Teppei; Kaneko, Naoko; Ajioka, Itsuki; Nakaguchi, Kanako; Omata, Taichi; Ohba, Honoka; Fässler, Reinhard; García-Verdugo, José Manuel; Sekiguchi, Kiyotoshi; Matsukawa, Noriyuki; Sawamoto, Kazunobu


    Cerebral ischemic stroke is a main cause of chronic disability. However, there is currently no effective treatment to promote recovery from stroke-induced neurological symptoms. Recent studies suggest that after stroke, immature neurons, referred to as neuroblasts, generated in a neurogenic niche, the ventricular-subventricular zone, migrate toward the injured area, where they differentiate into mature neurons. Interventions that increase the number of neuroblasts distributed at and around the lesion facilitate neuronal repair in rodent models for ischemic stroke, suggesting that promoting neuroblast migration in the post-stroke brain could improve efficient neuronal regeneration. To move toward the lesion, neuroblasts form chain-like aggregates and migrate along blood vessels, which are thought to increase their migration efficiency. However, the molecular mechanisms regulating these migration processes are largely unknown. Here we studied the role of β1-class integrins, transmembrane receptors for extracellular matrix proteins, in these migrating neuroblasts. We found that the neuroblast chain formation and blood vessel-guided migration critically depend on β1 integrin signaling. β1 integrin facilitated the adhesion of neuroblasts to laminin and the efficient translocation of their soma during migration. Moreover, artificial laminin-containing scaffolds promoted neuroblast chain formation and migration toward the injured area. These data suggest that laminin signaling via β1 integrin supports vasculature-guided neuronal migration to efficiently supply neuroblasts to injured areas. This study also highlights the importance of vascular scaffolds for cell migration in development and regeneration.

  17. Macrolide analog F806 suppresses esophageal squamous cell carcinoma (ESCC) by blocking β1 integrin activation. (United States)

    Li, Li-Yan; Jiang, Hong; Xie, Yang-Min; Liao, Lian-Di; Cao, Hui-Hui; Xu, Xiu-E; Chen, Bo; Zeng, Fa-Min; Zhang, Ying-Li; Du, Ze-Peng; Chen, Hong; Huang, Wei; Jia, Wei; Zheng, Wei; Xie, Jian-Jun; Li, En-Min; Xu, Li-Yan


    The paucity of new drugs for the treatment of esophageal squamous cell carcinoma (ESCC) limits the treatment options. This study characterized the therapeutic efficacy and action mechanism of a novel natural macrolide compound F806 in human ESCC xenograft models and cell lines. F806 inhibited growth of ESCC, most importantly, it displayed fewer undesirable side effects on normal tissues in two human ESCC xenograft models. F806 inhibited proliferation of six ESCC cells lines, with the half maximal inhibitory concentration (IC50) ranging from 9.31 to 16.43 μM. Furthermore, F806 induced apoptosis of ESCC cells, contributing to its growth-inhibitory effect. Also, F806 inhibited cell adhesion resulting in anoikis. Mechanistic studies revealed that F806 inhibited the activation of β1 integrin in part by binding to a novel site Arg610 of β1 integrin, suppressed focal adhesion formation, decreased cell adhesion to extracellular matrix and eventually triggered apoptosis. We concluded that F806 would potentially be a well-tolerated anticancer drug by targeting β1 integrin, resulting in anoikis in ESCC cells.

  18. Fluvastatin attenuates the down-regulation of β1 integrin expression in PAN-treated podocytes by inhibiting ROS

    Institute of Scientific and Technical Information of China (English)



    Objective To investigate the effect of fluvastatin(FLV) on the expression of β1 integrin in puromycin aminonucleoside(PAN)-treated podocytes and its mechanism. Methods Cultured human podocytes were divided into PAN,different concentrations of

  19. β1 Integrins Are Critically Involved in Neutrophil Locomotion in Extravascular Tissue In Vivo (United States)

    Werr, Joachim; Xie, Xun; Hedqvist, Per; Ruoslahti, Erkki; Lindbom, Lennart


    Recruitment of leukocytes from blood to tissue in inflammation requires the function of specific cell surface adhesion molecules. The objective of this study was to identify adhesion molecules that are involved in polymorphonuclear leukocyte (PMN) locomotion in extravascular tissue in vivo. Extravasation and interstitial tissue migration of PMNs was induced in the rat mesentery by chemotactic stimulation with platelet-activating factor (PAF; 10−7 M). Intravital time-lapse videomicroscopy was used to analyze migration velocity of the activated PMNs, and the modulatory influence on locomotion of locally administered antibodies or peptides recognizing various integrin molecules was examined. Immunofluorescence flow cytometry revealed increased expression of α4, β1, and β2 integrins on extravasated PMNs compared with blood PMNs. Median migration velocity in response to PAF stimulation was 15.5 ± 4.5 μm/min (mean ± SD). Marked reduction (67 ± 7%) in motility was observed after treatment with mAb blocking β1 integrin function (VLA integrins), whereas there was little, although significant, reduction (22 ± 13%) with β2 integrin mAb. Antibodies or integrin-binding peptides recognizing α4β1, α5β1, or αvβ3 were ineffective in modulating migration velocity. Our data demonstrate that cell surface expression of β1 integrins, although limited on blood PMNs, is induced in extravasated PMNs, and that members of the β1 integrin family other than α4β1 and α5β1 are critically involved in the chemokinetic movement of PMNs in rat extravascular tissue in vivo. PMID:9625769

  20. Functional analysis of alpha 1 beta 1 integrin in human natural killer cells. (United States)

    Pérez-Villar, J J; Melero, I; Gismondi, A; Santoni, A; López-Botet, M


    Upon activation with interleukin (IL)-2 human natural killer (NK) cells acquire on their surface the alpha 1 beta 1 and alpha 2 beta 1 integrins and down-regulate the expression of alpha 6 beta 1. By employing alpha 1 beta 1-specific monoclonal antibody (mAb) HP-2B6, characterized in our laboratory, we examined the functional role of the alpha 1 beta 1 integrin in NK cells. Treatment with HP-2B6 mAb partially interfered with attachment of cultured NK cells to type I collagen, and combined with an anti-alpha 2 beta 1 (TEA 1/41) mAb, it completely abrogated cell adhesion to this extracelular matrix protein. In contrast, NK cell attachment to laminin was completely blocked by the anti-beta 1 LIA 1/2 mAb, but was unaffected by alpha 1 and alpha 2-specific mAb; as alpha 3 beta 1 and alpha 6 beta 1 were undetectable, the data indicate that the alpha 1 beta 1 integrin binding sites for type I collagen and laminin are different. Incubation with anti-alpha 1 HP-2B6 or its F(ab')2 fragments specifically induced a rapid homotypic aggregation of NK cells that was dependent on active metabolism, an intact cytoskeleton and the presence of divalent cations (Ca2+ and Mg2+); homotypic cell adhesion was selectively blocked by anti-CD18, CD11a or CD54 mAb. In addition, stimulation of cultured NK cells with the anti-alpha 1 HP-2B6 enhanced TNF-alpha production and induced tyrosine phosphorylation of a 110-kDa protein. Pretreatment with specific inhibitors of protein tyrosine kinase (PTK) activity (tyrphostin 25 and herbimycin A) completely abrogated the functional effects induced by the anti-alpha 1 HP-2B6 mAb. Our data show that ligation of the alpha 1 beta 1 integrin positively modulates IL-2-activated NK cell function via a PTK-dependent pathway.

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

    Energy Technology Data Exchange (ETDEWEB)

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


    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.

  2. Distinct ErbB2 receptor populations differentially interact with beta1 integrin in breast cancer cell models (United States)

    Toscani, Andrés Martín; Sampayo, Rocío G.; Barabas, Federico Martín; Fuentes, Federico; Simian, Marina


    ErbB2 is a member of the ErbB family of tyrosine kinase receptors that plays a major role in breast cancer progression. Located at the plasma membrane, ErbB2 forms large clusters in spite of the presence of growth factors. Beta1 integrin, membrane receptor of extracellular matrix proteins, regulates adhesion, migration and invasiveness of breast cancer cells. Physical interaction between beta1 integrin and ErbB2 has been suggested although published data are contradictory. The aim of the present work was to study the interaction between ErbB2 and beta1 integrin in different scenarios of expression and activation. We determined that beta1 integrin and ErbB2 colocalization is dependent on the expression level of both receptors exclusively in adherent cells. In suspension cells, lack of focal adhesions leave integrins free to diffuse on the plasma membrane and interact with ErbB2 even at low expression levels of both receptors. In adherent cells, high expression of beta1 integrin leaves unbound receptors outside focal complexes that diffuse within the plasma membrane and interact with ErbB2 membrane domains. Superresolution imaging showed the existence of two distinct populations of ErbB2: a major population located in large clusters and a minor population outside these structures. Upon ErbB2 overexpression, receptors outside large clusters can freely diffuse at the membrane and interact with integrins. These results reveal how expression levels of beta1 integrin and ErbB2 determine their frequency of colocalization and show that extracellular matrix proteins shape membrane clusters distribution, regulating ErbB2 and beta1 integrin activity in breast cancer cells. PMID:28306722

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

    LENUS (Irish Health Repository)

    Andrews, E J


    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.

  4. Lipid raft regulates the initial spreading of melanoma A375 cells by modulating β1 integrin clustering. (United States)

    Wang, Ruifei; Bi, Jiajia; Ampah, Khamal Kwesi; Zhang, Chunmei; Li, Ziyi; Jiao, Yang; Wang, Xiaoru; Ba, Xueqing; Zeng, Xianlu


    Cell adhesion and spreading require integrins-mediated cell-extracellular matrix interaction. Integrins function through binding to extracellular matrix and subsequent clustering to initiate focal adhesion formation and actin cytoskeleton rearrangement. Lipid raft, a liquid ordered plasma membrane microdomain, has been reported to play major roles in membrane motility by regulating cell surface receptor function. Here, we identified that lipid raft integrity was required for β1 integrin-mediated initial spreading of melanoma A375 cells on fibronectin. We found that lipid raft disruption with methyl-β-cyclodextrin led to the inability of focal adhesion formation and actin cytoskeleton rearrangement by preventing β1 integrin clustering. Furthermore, we explored the possible mechanism by which lipid raft regulates β1 integrin clustering and demonstrated that intact lipid raft could recruit and modify some adaptor proteins, such as talin, α-actinin, vinculin, paxillin and FAK. Lipid raft could regulate the location of these proteins in lipid raft fractions and facilitate their binding to β1 integrin, which may be crucial for β1 integrin clustering. We also showed that lipid raft disruption impaired A375 cell migration in both transwell and wound healing models. Together, these findings provide a new insight for the relationship between lipid raft and the regulation of integrins.

  5. Beta1 integrins activate a MAPK signalling pathway in neural stem cells that contributes to their maintenance

    DEFF Research Database (Denmark)

    Campos, Lia S; Leone, Dino P; Relvas, Joao B;


    The emerging evidence that stem cells develop in specialised niches highlights the potential role of environmental factors in their regulation. Here we examine the role of beta1 integrin/extracellular matrix interactions in neural stem cells. We find high levels of beta1 integrin expression...... in the stem-cell containing regions of the embryonic CNS, with associated expression of the laminin alpha2 chain. Expression levels of laminin alpha2 are reduced in the postnatal CNS, but a population of cells expressing high levels of beta1 remains. Using neurospheres - aggregate cultures, derived from...... single stem cells, that have a three-dimensional architecture that results in the localisation of the stem cell population around the edge of the sphere - we show directly that beta1 integrins are expressed at high levels on neural stem cells and can be used for their selection. MAPK, but not PI3K...

  6. Beta1 integrin inhibits apoptosis induced by cyclic stretch in annulus fibrosus cells via ERK1/2 MAPK pathway. (United States)

    Zhang, Kai; Ding, Wei; Sun, Wei; Sun, Xiao-jiang; Xie, You-zhuan; Zhao, Chang-qing; Zhao, Jie


    Low back pain is associated with intervertebral disc degeneration (IVDD) due to cellular loss through apoptosis. Mechanical factors play an important role in maintaining the survival of the annulus fibrosus (AF) cells and the deposition of extracellular matrix. However, the mechanisms that excessive mechanical forces lead to AF cell apoptosis are not clear. The present study was to look for how AF cells sense mechanical changes. In vivo experiments, the involvement of mechanoreceptors in apoptosis was examined by RT-PCR and/or immunoblotting in the lumbar spine of rats subjected to unbalanced dynamic and static forces. In vitro experiments, we investigated apoptotic signaling pathways in untransfected and transfected AF cells with the lentivirus vector for rat β1 integrin overexpression after cyclic stretch. Apoptosis in AF cells was assessed using flow cytometry, Hoechst 33258 nuclear staining. Western blotting was used to analyze expression of β1 integrin and caspase-3 and ERK1/2 MAPK signaling molecules. In the rat IVDD model, unbalanced dynamic and static forces induced apoptosis of disc cells, which corresponded to decreased expression of β1 integrin. Cyclic stretch-induced apoptosis in rat AF cells correlated with the activation of caspase-3 and with decreased levels of β1 integrin and the phosphorylation levels of ERK1/2 activation level. However, the overexpression of β1 integrin in AF cells ameliorated cyclic stretch-induced apoptosis and decreased caspase-3 activation. Furthermore, ERK1/2-specific inhibitor promotes apoptosis in vector β1-infected AF cells. These results suggest that the disruption of β1 integrin signaling may underlie disc cell apoptosis induced by mechanical stress. Further work is necessary to fully elucidate the pathophysiological mechanisms that underlie IVDD caused by unbalanced dynamic and static forces.

  7. Helicobacter pylori type IV secretion apparatus exploits beta1 integrin in a novel RGD-independent manner.

    Directory of Open Access Journals (Sweden)

    Luisa F Jiménez-Soto


    Full Text Available Translocation of the Helicobacter pylori (Hp cytotoxin-associated gene A (CagA effector protein via the cag-Type IV Secretion System (T4SS into host cells is a major risk factor for severe gastric diseases, including gastric cancer. However, the mechanism of translocation and the requirements from the host cell for that event are not well understood. The T4SS consists of inner- and outer membrane-spanning Cag protein complexes and a surface-located pilus. Previously an arginine-glycine-aspartate (RGD-dependent typical integrin/ligand type interaction of CagL with alpha5beta1 integrin was reported to be essential for CagA translocation. Here we report a specific binding of the T4SS-pilus-associated components CagY and the effector protein CagA to the host cell beta1 Integrin receptor. Surface plasmon resonance measurements revealed that CagA binding to alpha5beta1 integrin is rather strong (dissociation constant, K(D of 0.15 nM, in comparison to the reported RGD-dependent integrin/fibronectin interaction (K(D of 15 nM. For CagA translocation the extracellular part of the beta1 integrin subunit is necessary, but not its cytoplasmic domain, nor downstream signalling via integrin-linked kinase. A set of beta1 integrin-specific monoclonal antibodies directed against various defined beta1 integrin epitopes, such as the PSI, the I-like, the EGF or the beta-tail domain, were unable to interfere with CagA translocation. However, a specific antibody (9EG7, which stabilises the open active conformation of beta1 integrin heterodimers, efficiently blocked CagA translocation. Our data support a novel model in which the cag-T4SS exploits the beta1 integrin receptor by an RGD-independent interaction that involves a conformational switch from the open (extended to the closed (bent conformation, to initiate effector protein translocation.

  8. ADAM12 induces actin cytoskeleton and extracellular matrix reorganization during early adipocyte differentiation by regulating beta1 integrin function

    DEFF Research Database (Denmark)

    Kawaguchi, Nobuko; Sundberg, Christina; Kveiborg, Marie


    -100 from cells overexpressing ADAM12 than from control cells. Collectively, these results show that surface expression of ADAM12 impairs the function of beta1 integrins and, consequently, alters the organization of the actin cytoskeleton and extracellular matrix. These events may be necessary....... Moreover, ADAM12-expressing cells were more prone to apoptosis, which could be prevented by treating the cells with beta1-activating antibodies. A reduced and re-organized fibronectin-rich extracellular matrix accompanied these changes. In addition, beta1 integrin was more readily extracted with Triton X...

  9. Glycoprotein VI but not alpha2beta1 integrin is essential for platelet interaction with collagen

    DEFF Research Database (Denmark)

    Nieswandt, B; Brakebusch, C; Bergmeier, W


    Platelet adhesion on and activation by components of the extracellular matrix are crucial to arrest post-traumatic bleeding, but can also harm tissue by occluding diseased vessels. Integrin alpha2beta1 is thought to be essential for platelet adhesion to subendothelial collagens, facilitating...... subsequent interactions with the activating platelet collagen receptor, glycoprotein VI (GPVI). Here we show that Cre/loxP-mediated loss of beta1 integrin on platelets has no significant effect on the bleeding time in mice. Aggregation of beta1-null platelets to native fibrillar collagen is delayed......, but not reduced, whereas aggregation to enzymatically digested soluble collagen is abolished. Furthermore, beta1-null platelets adhere to fibrillar, but not soluble collagen under static as well as low (150 s(-1)) and high (1000 s(-1)) shear flow conditions, probably through binding of alphaIIbbeta3 to von...

  10. Contribution of alpha4beta1 integrin to the antiallergic effect of levocabastine. (United States)

    Qasem, Ahmed R; Bucolo, Claudio; Baiula, Monica; Spartà, Antonino; Govoni, Paolo; Bedini, Andrea; Fascì, Domenico; Spampinato, Santi


    Levocabastine is an antiallergic drug acting as a histamine H1-receptor antagonist. In allergic conjunctivitis (AC), it may also antagonize up-regulation of the intercellular adhesion molecule-1 (ICAM-1) expressed on epithelial conjunctival cells. However, little is known about its effects on eosinophils, important effector cells in AC. The adhesion molecule integrin alpha(4)beta(1) is expressed in eosinophils; it interacts with the vascular cell adhesion molecule-1 (VCAM-1) and fibronectin (FN) in vascular endothelial cells and contributes to eosinophil activation and infiltration in AC. This study provides evidence that in a scintillation proximity assay levocabastine (IC(50) 406 microM), but not the first-generation antihistamine chlorpheniramine, displaced (125)I-FN binding to human integrin alpha(4)beta(1) and, in flow cytometry analysis, levocabastine antagonized the binding of a primary antibody to integrin alpha(4) expressed on the Jurkat cell surface. Levocabastine, but not chlorpheniramine, binds the alpha(4)beta(1) integrin and prevents eosinophil adhesion to VCAM-1, FN or human umbilical vascular endothelial cells (HUVEC) in vitro. Similarly, levocabastine affects alpha(L)beta(2)/ICAM-1-mediated adhesion of Jurkat cells. In a model of AC levocabastine eye drops reduced the clinical aspects of the late-phase reaction and the conjunctival expression of alpha(4)beta(1) integrin by reducing infiltrated eosinophils. We propose that blockade of integrin-mediated cell adhesion might be a target of the antiallergic action of levocabastine and may play a role in preventing eosinophil adhesion and infiltration in AC.

  11. A dual role for integrin-linked kinase and β1-integrin in modulating cardiac aging. (United States)

    Nishimura, Mayuko; Kumsta, Caroline; Kaushik, Gaurav; Diop, Soda B; Ding, Yun; Bisharat-Kernizan, Jumana; Catan, Hannah; Cammarato, Anthony; Ross, Robert S; Engler, Adam J; Bodmer, Rolf; Hansen, Malene; Ocorr, Karen


    Cardiac performance decreases with age, which is a major risk factor for cardiovascular disease and mortality in the aging human population, but the molecular mechanisms underlying cardiac aging are still poorly understood. Investigating the role of integrin-linked kinase (ilk) and β1-integrin (myospheroid, mys) in Drosophila, which colocalize near cardiomyocyte contacts and Z-bands, we find that reduced ilk or mys function prevents the typical changes of cardiac aging seen in wildtype, such as arrhythmias. In particular, the characteristic increase in cardiac arrhythmias with age is prevented in ilk and mys heterozygous flies with nearly identical genetic background, and they live longer, in line with previous findings in Caenorhabditis elegans for ilk and in Drosophila for mys. Consistent with these findings, we observed elevated β1-integrin protein levels in old compared with young wild-type flies, and cardiac-specific overexpression of mys in young flies causes aging-like heart dysfunction. Moreover, moderate cardiac-specific knockdown of integrin-linked kinase (ILK)/integrin pathway-associated genes also prevented the decline in cardiac performance with age. In contrast, strong cardiac knockdown of ilk or ILK-associated genes can severely compromise cardiac integrity, including cardiomyocyte adhesion and overall heart function. These data suggest that ilk/mys function is necessary for establishing and maintaining normal heart structure and function, and appropriate fine-tuning of this pathway can retard the age-dependent decline in cardiac performance and extend lifespan. Thus, ILK/integrin-associated signaling emerges as an important and conserved genetic mechanism in longevity, and as a new means to improve age-dependent cardiac performance, in addition to its vital role in maintaining cardiac integrity.

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

    DEFF Research Database (Denmark)

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


    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-...

  13. Glycosylation modulates melanoma cell α2β1 and α3β1 integrin interactions with type IV collagen. (United States)

    Stawikowski, Maciej J; Aukszi, Beatrix; Stawikowska, Roma; Cudic, Mare; Fields, Gregg B


    Although type IV collagen is heavily glycosylated, the influence of this post-translational modification on integrin binding has not been investigated. In the present study, galactosylated and nongalactosylated triple-helical peptides have been constructed containing the α1(IV)382-393 and α1(IV)531-543 sequences, which are binding sites for the α2β1 and α3β1 integrins, respectively. All peptides had triple-helical stabilities of 37 °C or greater. The galactosylation of Hyl(393) in α1(IV)382-393 and Hyl(540) and Hyl(543) in α1(IV)531-543 had a dose-dependent influence on melanoma cell adhesion that was much more pronounced in the case of α3β1 integrin binding. Molecular modeling indicated that galactosylation occurred on the periphery of α2β1 integrin interaction with α1(IV)382-393 but right in the middle of α3β1 integrin interaction with α1(IV)531-543. The possibility of extracellular deglycosylation of type IV collagen was investigated, but no β-galactosidase-like activity capable of collagen modification was found. Thus, glycosylation of collagen can modulate integrin binding, and levels of glycosylation could be altered by reduction in expression of glycosylation enzymes but most likely not by extracellular deglycosylation activity.

  14. Selective, α2β1 integrin-dependent secretion of il-6 by connective tissue mast cells. (United States)

    McCall-Culbreath, Karissa D; Li, Zhengzhi; Zhang, Zhonghua; Lu, Lucy X; Orear, Lynda; Zutter, Mary M


    Mast cells, critical mediators of inflammation and anaphylaxis, are poised as one of the first lines of defense against external assault. Mast cells release several classes of preformed and de novo synthesized mediators. Cross-linking of the high-affinity FcεRI results in degranulation and the release of preformed, proinflammatory mediators including histamine and serotonin. We previously demonstrated that mast cell activation by Listeria monocytogenes requires the α2β1 integrin for rapid IL-6 secretion both in vivo and in vitro. However, the mechanism of IL-6 release is unknown. Here, we demonstrate the Listeria- and α2β1 integrin-mediated mast cell release of preformed IL-6 without the concomitant release of histamine or β-hexosaminidase. α2β1 integrin-dependent mast cell activation and IL-6 release is calcium independent. In contrast, IgE cross-linking-mediated degranulation is calcium dependent and does not result in IL-6 release, demonstrating that distinct stimuli result in the release of specific mediator pools. These studies demonstrate that IL-6 is presynthesized and stored in connective tissue mast cells and can be released from mast cells in response to distinct, α2β1 integrin-dependent stimulation, providing the host with a specific innate immune response without stimulating an allergic reaction.

  15. α1- and α5-containing laminins regulate the development of bile ducts via β1 integrin signals. (United States)

    Tanimizu, Naoki; Kikkawa, Yamato; Mitaka, Toshihiro; Miyajima, Atsushi


    Signals derived from basal lamina components are important for developing three-dimensional architecture of epithelial tissues. Laminins consisting of α, β, and γ subunits in basal lamina play pivotal roles in the formation and maintenance of epithelial tissue structures. However, it remains unclear which laminin isoforms transmit signals and how epithelial cells receive them to regulate multiple developmental processes. In three-dimensional culture of a liver progenitor cell line, Hepatic Progenitor Cells Proliferating on Laminin (HPPL), the cells establish apicobasal polarity and form cysts with a central lumen. Neutralizing antibody against β1 integrin blocked the formation and maintenance of the cyst structure, indicating that β1 integrin signaling was necessary throughout the morphogenesis. Although the addition of α1-containing laminin, a ligand of β1 integrin, induced cyst formation, it was dispensable for the maintenance of the cyst, suggesting that HPPL produces another ligand for β1 integrin to maintain the structure. Indeed, we found that HPPL produced α5-containing laminin, and siRNA against laminin α5 partially inhibited the lumen formation. In fetal liver, p75NTR(+) periportal fibroblasts and bile duct epithelial cells, known as cholangiocytes, expressed α1- and α5-containing laminins, respectively. In laminin α5 KO liver, cholangiocytes normally emerged, but the number of bile ducts was decreased. These results suggest that α1-containing laminin is sufficient as a component of the basal lamina for the commitment of bipotential liver progenitors to cholangiocytes and the apicobasal polarization, whereas α5-containing laminin is necessary for the formation of mature duct structures. Thus, α1- and α5-containing laminins differentially regulate the sequential events to form epithelial tissues via β1 integrin signals.

  16. Persistent cell migration and adhesion rely on retrograde transport of β(1) integrin. (United States)

    Shafaq-Zadah, Massiullah; Gomes-Santos, Carina S; Bardin, Sabine; Maiuri, Paolo; Maurin, Mathieu; Iranzo, Julian; Gautreau, Alexis; Lamaze, Christophe; Caswell, Patrick; Goud, Bruno; Johannes, Ludger


    Integrins have key functions in cell adhesion and migration. How integrins are dynamically relocalized to the leading edge in highly polarized migratory cells has remained unexplored. Here, we demonstrate that β1 integrin (known as PAT-3 in Caenorhabditis elegans), but not β3, is transported from the plasma membrane to the trans-Golgi network, to be resecreted in a polarized manner. This retrograde trafficking is restricted to the non-ligand-bound conformation of β1 integrin. Retrograde trafficking inhibition abrogates several β1-integrin-specific functions such as cell adhesion in early embryonic development of mice, and persistent cell migration in the developing posterior gonad arm of C. elegans. Our results establish a paradigm according to which retrograde trafficking, and not endosomal recycling, is the key driver for β1 integrin function in highly polarized cells. These data more generally suggest that the retrograde route is used to relocalize plasma membrane machinery from previous sites of function to the leading edge of migratory cells.

  17. Lymphocyte crawling and transendothelial migration require chemokine triggering of high-affinity LFA-1 integrin. (United States)

    Shulman, Ziv; Shinder, Vera; Klein, Eugenia; Grabovsky, Valentin; Yeger, Orna; Geron, Erez; Montresor, Alessio; Bolomini-Vittori, Matteo; Feigelson, Sara W; Kirchhausen, Tomas; Laudanna, Carlo; Shakhar, Guy; Alon, Ronen


    Endothelial chemokines are instrumental for integrin-mediated lymphocyte adhesion and transendothelial migration (TEM). By dissecting how chemokines trigger lymphocyte integrins to support shear-resistant motility on and across cytokine-stimulated endothelial barriers, we found a critical role for high-affinity (HA) LFA-1 integrin in lymphocyte crawling on activated endothelium. Endothelial-presented chemokines triggered HA-LFA-1 and adhesive filopodia at numerous submicron dots scattered underneath crawling lymphocytes. Shear forces applied to endothelial-bound lymphocytes dramatically enhanced filopodia density underneath crawling lymphocytes. A fraction of the adhesive filopodia invaded the endothelial cells prior to and during TEM and extended large subluminal leading edge containing dots of HA-LFA-1 occupied by subluminal ICAM-1. Memory T cells generated more frequent invasive filopodia and transmigrated more rapidly than their naive counterparts. We propose that shear forces exerted on HA-LFA-1 trigger adhesive and invasive filopodia at apical endothelial surfaces and thereby promote lymphocyte crawling and probing for TEM sites.

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

    Institute of Scientific and Technical Information of China (English)

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


    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.

  19. The Effect of Conditional Inactivation of Beta 1 Integrins using Twist 2 Cre, Osterix Cre and Osteocalcin Cre Lines on Skeletal Phenotype (United States)

    Shekaran, Asha; Shoemaker, James T.; Kavanaugh, Taylor E.; Lin, Angela S.; LaPlaca, Michelle C.; Fan, Yuhong; Guldberg, Robert E.; García, Andrés J.


    Skeletal development and growth are complex processes regulated by multiple microenvironmental cues, including integrin-ECM interactions. The β1 sub-family of integrins is the largest integrin sub-family and constitutes the main integrin binding partners of collagen I, the major ECM component of bone. As complete β1 integrin integrin knockout results in embryonic lethality, studies of β1 integrin function in vivo rely on tissue-specific gene deletions. While multiple in vitro studies indicate that β1 integrins are crucial regulators of osteogenesis and mineralization, in vivo osteoblast-specific perturbations of β1 integrins have resulted in mild and sometimes contradictory skeletal phenotypes. To further investigate the role of β1 integrins on skeletal phenotype, we used the Twist2-Cre, Osterix-Cre and Osteocalcin-Cre lines to generate conditional β1 integrin deletions, where cre is expressed primarily in mesenchymal condensation, pre-osteoblast, and mature osteoblast lineage cells respectively within these lines. Mice with Twist2-specific β1 integrin disruption were smaller, had impaired skeletal development, especially in the craniofacial and vertebral tissues at E19.5, and did not survive beyond birth. Osterix-specific β1 integrin deficiency resulted in viable mice which were normal at birth but displayed early defects in calvarial ossification, incisor eruption and growth as well as femoral bone mineral density, structure, and mechanical properties. Although these defects persisted into adulthood, they became milder with age. Finally, a lack of β1 integrins in mature osteoblasts and osteocytes resulted in minor alterations to femur structure but had no effect on mineral density, biomechanics or fracture healing. Taken together, our data indicate that β1 integrin expression in early mesenchymal condensations play an important role in skeletal ossification, while β1 integrin-ECM interactions in pre-osteoblast, odontoblast- and hypertrophic

  20. Mechanotransduction molecules in the plant gravisensory response: amyloplast/statolith membranes contain a beta 1 integrin-like protein (United States)

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


    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.

  1. Functional blockade of α5β1 integrin induces scattering and genomic landscape remodeling of hepatic progenitor cells

    Directory of Open Access Journals (Sweden)

    Lorenti Alicia


    Full Text Available Abstract Background Cell scattering is a physiological process executed by stem and progenitor cells during embryonic liver development and postnatal organ regeneration. Here, we investigated the genomic events occurring during this process induced by functional blockade of α5β1 integrin in liver progenitor cells. Results Cells treated with a specific antibody against α5β1 integrin exhibited cell spreading and scattering, over-expression of liver stem/progenitor cell markers and activation of the ERK1/2 and p38 MAPKs signaling cascades, in a similar manner to the process triggered by HGF/SF1 stimulation. Gene expression profiling revealed marked transcriptional changes of genes involved in cell adhesion and migration, as well as genes encoding chromatin remodeling factors. These responses were accompanied by conspicuous spatial reorganization of centromeres, while integrin genes conserved their spatial positioning in the interphase nucleus. Conclusion Collectively, our results demonstrate that α5β1 integrin functional blockade induces cell migration of hepatic progenitor cells, and that this involves a dramatic remodeling of the nuclear landscape.

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

    DEFF Research Database (Denmark)

    Cordes, N; Seidler, J; Durzok, R;


    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 ...... in tumor cells may promote the development of innovative molecular-targeted therapeutic antitumor strategies.......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...... signaling-incompetent beta1B variants. Cells grown on fibronectin, collagen-III, beta1-integrin-IgG or poly-l-lysine were exposed to 0-6 Gy X-rays in presence or depletion of growth factors and phosphatidylinositol-3 kinase (PI3K) inhibitors (LY294002, wortmannin). In order to test the relevance...

  3. alpha2beta1 integrin controls association of Rac with the membrane and triggers quiescence of endothelial cells. (United States)

    Cailleteau, Laurence; Estrach, Soline; Thyss, Raphael; Boyer, Laurent; Doye, Anne; Domange, Barbara; Johnsson, Nils; Rubinstein, Eric; Boucheix, Claude; Ebrahimian, Teni; Silvestre, Jean-Sebastien; Lemichez, Emmanuel; Meneguzzi, Guerrino; Mettouchi, Amel


    Integrin receptors and their extracellular matrix ligands provide cues to cell proliferation, survival, differentiation and migration. Here, we show that alpha2beta1 integrin, when ligated to the basement membrane component laminin-1, triggers a proliferation arrest in primary endothelial cells. Indeed, in the presence of strong growth signals supplied by growth factors and fibronectin, alpha2beta1 engagement alters assembly of mature focal adhesions by alpha5beta1 and leads to impairment of downstream signaling and cell-cycle arrest in the G1 phase. Although the capacity of alpha5beta1 to signal for GTP loading of Rac is preserved, the joint engagement of alpha2beta1 interferes with membrane anchorage of Rac. Adapting the 'split-ubiquitin' sensor to screen for membrane-proximal alpha2 integrin partners, we identified the CD9 tetraspanin and further establish its requirement for destabilization of focal adhesions, control of Rac subcellular localization and growth arrest induced by alpha2beta1 integrin. Altogether, our data establish that alpha2beta1 integrin controls endothelial cell commitment towards quiescence by triggering a CD9-dependent dominant signaling.

  4. RECK-Mediated β1-Integrin Regulation by TGF-β1 Is Critical for Wound Contraction in Mice (United States)

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


    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

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

    DEFF Research Database (Denmark)

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


    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...... that 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...... lacking both alpha(2)beta(1) integrin and the activating collagen receptor GPVI responded normally to rhodocytin. Finally, even after additional proteolytic removal of the 45-kDa N-terminal domain of GPIbalpha rhodocytin induced aggregation of these platelets. These results demonstrate that rhodocytin...

  6. Reverted austenite in PH 13-8 Mo maraging steels

    Energy Technology Data Exchange (ETDEWEB)

    Schnitzer, Ronald, E-mail: [Christian Doppler Laboratory for Early Stages of Precipitation, University of Leoben, Franz-Josef-Strasse 18, A-8700 Leoben (Austria); Radis, Rene [Christian Doppler Laboratory for Early Stages of Precipitation, Vienna University of Technology, Favoritenstrasse 9-11, A-1040 Vienna (Austria); Institute for Materials Science and Welding, Graz University of Technology, Kopernikusgasse 24, A-8010 Graz (Austria); Noehrer, Matthias [Christian Doppler Laboratory for Early Stages of Precipitation, University of Leoben, Franz-Josef-Strasse 18, A-8700 Leoben (Austria); Schober, Michael [Department of Physical Metallurgy and Materials Testing, University of Leoben, Franz-Josef-Strasse 18, A-8700 Leoben (Austria); Hochfellner, Rainer [Christian Doppler Laboratory for Early Stages of Precipitation, University of Leoben, Franz-Josef-Strasse 18, A-8700 Leoben (Austria); Zinner, Silvia [Boehler Edelstahl GmbH and Co KG, Mariazeller Strasse 25, A-8605 Kapfenberg (Austria); Povoden-Karadeniz, E.; Kozeschnik, Ernst [Christian Doppler Laboratory for Early Stages of Precipitation, Vienna University of Technology, Favoritenstrasse 9-11, A-1040 Vienna (Austria); Leitner, Harald [Christian Doppler Laboratory for Early Stages of Precipitation, University of Leoben, Franz-Josef-Strasse 18, A-8700 Leoben (Austria); Department of Physical Metallurgy and Materials Testing, University of Leoben, Franz-Josef-Strasse 18, A-8700 Leoben (Austria)


    The mechanical properties of maraging steels are strongly influenced by the presence of reverted austenite. In this study, the morphology and chemical composition of reverted austenite in a corrosion resistant maraging steel was characterized using transmission electron microscopy (TEM) and atom probe tomography (APT). Two types of austenite, i.e. granular and elongated, are present after aging at 575 {sup o}C, whereby the content of the latter increases during aging. The investigations revealed that the austenite phase is enriched in Ni, which prevents the transformation to martensite during cooling. Inside and next to the austenitc areas, Mo and Cr-rich carbides, which form during the aging treatment, were found. Various aging treatments were performed to obtain the activation energy for the formation of reverted austenite. Additionally, the experimental data are compared with thermodynamic and kinetic simulations. Based on these results and the chemical composition changes of the phases, a model for the formation of reverted austenite is presented. It is concluded that precipitation of B2-ordered NiAl and formation of reverted austenite take place simultaneously during aging and that dissolution of precipitates is not essential for the initial formation of reverted austenite.

  7. Prostate; Prostate

    Energy Technology Data Exchange (ETDEWEB)

    Rouviere, O.; Valette, O.; Grivolat, S.; Colin-Pangaud, C.; Bouvier, R.; Chapelon, J.Y.; Gelet, A.; Lyonnet, D.; Rouviere, O.; Mege-Lechevallier, F.; Chapelon, J.Y.; Gelet, A.; Bouvier, R.; Boutitie, F.; Lyonnet, D. [69 - Lyon (France)


    Two methods to detect recurrence of prostate cancer are presented. Dynamic magnetic resonance imaging after radiotherapy and color doppler after high intensity focused ultrasounds (but with patients that have not received a hormones therapy). These two methods presents an useful contribution. (N.C.)

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

    Energy Technology Data Exchange (ETDEWEB)

    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: [Temple University, Department of Biology, Philadelphia, PA 19122 (United States)


    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.

  9. Lateral Mobility and Nanoscale Spatial Arrangement of Chemokine-activated α4β1 Integrins on T Cells* (United States)

    Sosa-Costa, Alberto; Isern de Val, Sol; Sevilla-Movilla, Silvia; Teixidó, Joaquin


    Chemokine stimulation of integrin α4β1-dependent T lymphocyte adhesion is a key step during lymphocyte trafficking. A central question regarding α4β1 function is how its lateral mobility and organization influence its affinity and avidity following cell stimulation with chemokines and/or ligands. Using single particle tracking and superresolution imaging approaches, we explored the lateral mobility and spatial arrangement of individual α4β1integrins on T cells exposed to different activating stimuli. We show that CXCL12 stimulation leads to rapid and transient α4β1activation, measured by induction of the activation epitope recognized by the HUTS-21 anti-β1antibody and by increased talin-β1 association. CXCL12-dependent α4β1 activation directly correlated with restricted lateral diffusion and integrin immobilization. Moreover, co-stimulation by CXCL12 together with soluble VCAM-1 potentiated integrin immobilization with a 5-fold increase in immobile integrins compared with unstimulated conditions. Our data indicate that docking by talin of the chemokine-activated α4β1 to the actin cytoskeleton favors integrin immobilization, which likely facilitates ligand interaction and increased adhesiveness. Superresolution imaging showed that the nanoscale organization of high-affinity α4β1 remains unaffected following chemokine and/or ligand addition. Instead, newly activated α4β1 integrins organize on the cell membrane as independent units without joining pre-established integrin sites to contribute to cluster formation. Altogether, our results provide a rationale to understand how the spatiotemporal organization of activated α4β1 integrins regulates T lymphocyte adhesion. PMID:27481944

  10. Saccharomyces boulardii improves intestinal cell restitution through activation of the α2β1 integrin collagen receptor.

    Directory of Open Access Journals (Sweden)

    Alexandra Canonici

    Full Text Available Intestinal epithelial cell damage is frequently seen in the mucosal lesions of inflammatory bowel diseases such as ulcerative colitis or Crohn's disease. Complete remission of these diseases requires both the cessation of inflammation and the migration of enterocytes to repair the damaged epithelium. Lyophilized Saccharomyces boulardii (Sb, Biocodex is a nonpathogenic yeast widely used as a therapeutic agent for the treatment and prevention of diarrhea and other gastrointestinal disorders. In this study, we determined whether Sb could accelerate enterocyte migration. Cell migration was determined in Sb force-fed C57BL6J mice and in an in vitro wound model. The impact on α2β1 integrin activity was assessed using adhesion assays and the analysis of α2β1 mediated signaling pathways both in vitro and in vivo. We demonstrated that Sb secretes compounds that enhance the migration of enterocytes independently of cell proliferation. This enhanced migration was associated with the ability of Sb to favor cell-extracellular matrix interaction. Indeed, the yeast activates α2β1 integrin collagen receptors. This leads to an increase in tyrosine phosphorylation of cytoplasmic molecules, including focal adhesion kinase and paxillin, involved in the integrin signaling pathway. These changes are associated with the reorganization of focal adhesion structures. In conclusion Sb secretes motogenic factors that enhance cell restitution through the dynamic regulation of α2β1 integrin activity. This could be of major importance in the development of novel therapies targeting diseases characterized by severe mucosal injury, such as inflammatory and infectious bowel diseases.

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

    Energy Technology Data Exchange (ETDEWEB)

    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: [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)


    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

  12. αν and β1 Integrins mediate Aβ-induced neurotoxicity in hippocampal neurons via the FAK signaling pathway.

    Directory of Open Access Journals (Sweden)

    Hai-Yan Han

    Full Text Available αν and β1 integrins mediate Aβ-induced neurotoxicity in primary hippocampal neurons. We treated hippocampal neurons with 2.5 µg/mL 17E6 and 5 µg/mL ab58524, which are specific αν and β1 integrin antagonists, respectively, for 42 h prior to 10 µM Aβ treatment. Next, we employed small interfering RNA (siRNA to silence focal adhesion kinase (FAK, a downstream target gene of integrins. The siRNAs were designed with a target sequence, an MOI of 10 and the addition of 5 µg/mL polybrene. Under these conditions, the neurons were transfected and the apoptosis of different cell types was detected. Moreover, we used real-time PCR and Western blotting analyses to detect the expression of FAK and ρFAK genes in different cell types and investigated the underlying mechanism and signal pathway by which αν and β1 integrins mediate Aβ-induced neurotoxicity in hippocampal neurons. An MTT assay showed that both 17E6 and ab58524 significantly increased cell viability compared with the Aβ-treated neurons (P<0.01 and P<0.05, respectively. However, this protective effect was markedly attenuated after transfection with silencing FAK (siFAK. Moreover, TUNEL immunostaining and flow cytometry indicated that both 17E6 and ab58524 significantly protected hippocampal neurons against apoptosis induced by Aβ (P<0.05 compared with the Aβ-treated cells. However, this protective effect was reversed with siFAK treatment. Both the gene and protein expression of FAK increased after Aβ treatment. Interestingly, as the gene and protein levels of FAK decreased, the ρFAK protein expression markedly increased. Furthermore, both the gene and protein expression of FAK and ρFAK were significantly diminished. Thus, we concluded that both αν and β1 integrins interfered with Aβ-induced neurotoxicity in hippocampal neurons and that this mechanism partially contributes to the activation of the Integrin-FAK signaling pathway.

  13. Vascular endothelial growth factor-induced migration of multiple myeloma cells is associated with beta 1 integrin- and phosphatidylinositol 3-kinase-dependent PKC alpha activation. (United States)

    Podar, Klaus; Tai, Yu-Tzu; Lin, Boris K; Narsimhan, Radha P; Sattler, Martin; Kijima, Takashi; Salgia, Ravi; Gupta, Deepak; Chauhan, Dharminder; Anderson, Kenneth C


    In multiple myeloma (MM), migration is necessary for the homing of tumor cells to bone marrow (BM), for expansion within the BM microenvironment, and for egress into the peripheral blood. In the present study we characterize the role of vascular endothelial growth factor (VEGF) and beta(1) integrin (CD29) in MM cell migration. We show that protein kinase C (PKC) alpha is translocated to the plasma membrane and activated by adhesion of MM cells to fibronectin and VEGF. We identify beta(1) integrin modulating VEGF-triggered MM cell migration on fibronectin. We show that transient enhancement of MM cell adhesion to fibronectin triggered by VEGF is dependent on the activity of both PKC and beta(1) integrin. Moreover, we demonstrate that PKC alpha is constitutively associated with beta(1) integrin. These data are consistent with PKC alpha-dependent exocytosis of activated beta(1) integrin to the plasma membrane, where its increased surface expression mediates binding to fibronectin; conversely, catalytically active PKC alpha-driven internalization of beta(1) integrin results in MM cell de-adhesion. We show that the regulatory subunit of phosphatidylinositol (PI) 3-kinase (p85) is constitutively associated with FMS-like tyrosine kinase-1 (Flt-1). VEGF stimulates activation of PI 3-kinase, and both MM cell adhesion and migration are PI 3-kinase-dependent. Moreover, both VEGF-induced PI 3-kinase activation and beta(1) integrin-mediated binding to fibronectin are required for the recruitment and activation of PKC alpha. Time-lapse phase contrast video microscopy (TLVM) studies confirm the importance of these signaling components in VEGF-triggered MM cell migration on fibronectin.

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

    Directory of Open Access Journals (Sweden)

    Leanne Mortimer


    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.

  15. Alpha4beta1 integrin and erythropoietin mediate temporally distinct steps in erythropoiesis: integrins in red cell development. (United States)

    Eshghi, Shawdee; Vogelezang, Mariette G; Hynes, Richard O; Griffith, Linda G; Lodish, Harvey F


    Erythropoietin (Epo) is essential for the terminal proliferation and differentiation of erythroid progenitor cells. Fibronectin is an important part of the erythroid niche, but its precise role in erythropoiesis is unknown. By culturing fetal liver erythroid progenitors, we show that fibronectin and Epo regulate erythroid proliferation in temporally distinct steps: an early Epo-dependent phase is followed by a fibronectin-dependent phase. In each phase, Epo and fibronectin promote expansion by preventing apoptosis partly through bcl-xL. We show that alpha(4), alpha(5), and beta(1) are the principal integrins expressed on erythroid progenitors; their down-regulation during erythropoiesis parallels the loss of cell adhesion to fibronectin. Culturing erythroid progenitors on recombinant fibronectin fragments revealed that only substrates that engage alpha(4)beta(1)-integrin support normal proliferation. Collectively, these data suggest a two-phase model for growth factor and extracellular matrix regulation of erythropoiesis, with an early Epo-dependent, integrin-independent phase followed by an Epo-independent, alpha(4)beta(1)-integrin-dependent phase.

  16. Laminins 411 and 421 differentially promote tumor cell migration via α6β1 integrin and MCAM (CD146). (United States)

    Ishikawa, Taichi; Wondimu, Zenebech; Oikawa, Yuko; Gentilcore, Giusy; Kiessling, Rolf; Egyhazi Brage, Suzanne; Hansson, Johan; Patarroyo, Manuel


    α4-laminins, such as laminins 411 and 421, are mesenchymal laminins expressed by blood and lymphatic vessels and some tumor cells. Laminin-411 promotes migration of leukocytes and endothelial cells, but the effect of this laminin and laminin-421 on tumor cells is poorly understood. In the present study, we demonstrate that laminin-411 and, to a greater extent, laminin-421 significantly promote migration of tumor cells originated from melanomas, gliomas and different carcinomas via α6β1 integrin. In solid-phase binding assays, both laminins similarly bound α6β1 integrin but only laminin-421, among several laminin isoforms, readily bound MCAM (CD146), a cell-surface adhesion molecule strongly associated with tumor progression. Accordingly, a function-blocking mAb to MCAM inhibited tumor cell migration on laminin-421 but not on laminins 411 or 521. In tumor tissues, melanoma cells co-expressed MCAM, laminin α4, β1, β2 and γ1 chains, and integrin α6 and β1 chains. The present data highlight the novel role of α4-laminins in tumor cell migration and identify laminin-421 as a primary ligand for MCAM and a putative mediator of tumor invasion and metastasis.

  17. Carbon nanotubes enhance intercalated disc assembly in cardiac myocytes via the β1-integrin-mediated signaling pathway. (United States)

    Sun, Hongyu; Lü, Shuanghong; Jiang, Xiao-Xia; Li, Xia; Li, Hong; Lin, Qiuxia; Mou, Yongchao; Zhao, Yuwei; Han, Yao; Zhou, Jin; Wang, Changyong


    Carbon nanotubes (CNTs) offer a new paradigm for constructing functional cardiac patches and repairing myocardial infarction (MI). However, little is known about how CNTs enhance the mechanical integrity and electrophysiological function of cardiac myocytes. To address this issue, we investigated the regularity and precise mechanism of the influence of CNTs on the assembly of intercalated disc (IDs). Here, single walled CNTs incorporated into collagen substrates were utilized as growth supports for neonatal cardiomyocytes, which enhanced cardiomyocyte adhesion and maturation. Furthermore, through the use of immunohistochemical staining, western blotting, transmission electron microscopy, and intracellular calcium transient measurement, we discovered that the addition of CNTs remarkably increased ID-related protein expression and enhanced ID assembly and functionality. On that basis, we further explored the underlying mechanism for how CNTs enhanced ID assembly through the use of immunohistochemical staining and western blotting. We found that the β1-integrin-mediated signaling pathway mediated CNT-induced upregulation of electrical and mechanical junction proteins. Notably, CNTs remarkably accelerated gap junction formation via activation of the β1-integrin-mediated FAK/ERK/GATA4 pathway. These findings provide valuable insight into the mechanistic effects that CNTs have on neonatal cardiomyocyte performance and will have a significant impact on the future of nanomedical research.

  18. Alpha1beta1 integrin is crucial for accumulation of epidermal T cells and the development of psoriasis. (United States)

    Conrad, Curdin; Boyman, Onur; Tonel, Giulia; Tun-Kyi, Adrian; Laggner, Ute; de Fougerolles, Antonin; Kotelianski, Victor; Gardner, Humphrey; Nestle, Frank O


    Psoriasis is a common T cell-mediated autoimmune inflammatory disease. We show that blocking the interaction of alpha1beta1 integrin (VLA-1) with collagen prevented accumulation of epidermal T cells and immunopathology of psoriasis. Alpha1beta1 integrin, a major collagen-binding surface receptor, was exclusively expressed by epidermal but not dermal T cells. Alpha1beta1-positive T cells showed characteristic surface markers of effector memory cells and contained high levels of interferon-gamma but not interleukin-4. Blockade of alpha1beta1 inhibited migration of T cells into the epidermis in a clinically relevant xenotransplantation model. This was paralleled by a complete inhibition of psoriasis development, comparable to that caused by tumor necrosis factor-alpha blockers. These results define a crucial role for alpha1beta1 in controlling the accumulation of epidermal type 1 polarized effector memory T cells in a common human immunopathology and provide the basis for new strategies in psoriasis treatment focusing on T cell-extracellular matrix interactions.

  19. Successful therapeutic transplantation of revertant skin in epidermolysis bullosa

    NARCIS (Netherlands)

    Gostynski, Antoni; Pasmooij, Anna M. G.; Jonkman, Marcel F.


    Background: Epidermolysis bullosa (EB) is a group of genetic blistering diseases. Despite many efforts, treatment for EB remains symptomatic. Revertant mosaicism, coexistence of cells carrying disease-causing mutations with cells in which the inherited mutation is genetically corrected by a spontane

  20. Extinction Partially Reverts Structural Changes Associated with Remote Fear Memory (United States)

    Vetere, Gisella; Restivo, Leonardo; Novembre, Giovanni; Aceti, Massimiliano; Lumaca, Massimo; Ammassari-Teule, Martine


    Structural synaptic changes occur in medial prefrontal cortex circuits during remote memory formation. Whether extinction reverts or further reshapes these circuits is, however, unknown. Here we show that the number and the size of spines were enhanced in anterior cingulate (aCC) and infralimbic (ILC) cortices 36 d following contextual fear…

  1. Sulfonamide inhibitors of α2β1 integrin reveal the essential role of collagen receptors in in vivo models of inflammation. (United States)

    Nissinen, Liisa; Ojala, Marika; Langen, Barbara; Dost, Rita; Pihlavisto, Marjo; Käpylä, Jarmo; Marjamäki, Anne; Heino, Jyrki


    Small molecule inhibitors of α2β1 integrin, a major cellular collagen receptor, have been reported to inhibit platelet function, kidney injury, and angiogenesis. Since α2β1 integrin is abundantly expressed on various inflammation-associated cells, we tested whether recently developed α2β1 blocking sulfonamides have anti-inflammatory properties. Integrin α2β1 inhibitors were shown to reduce the signs of inflammation in arachidonic acid-induced ear edema, PAF stimulated air pouch, ovalbumin-induced skin hypersensitivity, adjuvant arthritis, and collagen-induced arthritis. Thus, these sulfonamides are potential drugs for acute and allergic inflammation, hypersensitivity, and arthritis. One sulfonamide with potent anti-inflammatory activity has previously been reported to be selective for activated integrins, but not to inhibit platelet function. Thus, the experiments also revealed fundamental differences in the action of nonactivated and activated α2β1 integrins in inflammation when compared to thrombosis.

  2. Activation of the FAK-src molecular scaffolds and p130Cas-JNK signaling cascades by alpha1-integrins during colon cancer cell invasion. (United States)

    Van Slambrouck, Severine; Grijelmo, Clara; De Wever, Olivier; Bruyneel, Erik; Emami, Shahin; Gespach, Christian; Steelant, Wim F A


    Increased src tyrosine kinase expression and activity has been associated with colon cancer cell invasion and survival. Several signaling pathways are involved in the oncogenic activation of src during the adenoma to carcinoma progression and cellular invasion. In the present study, the synthetic ether lipid analog ET-18-OMe was shown to promote invasion of HCT-8/S11 colon cancer cells into collagen type I through the concomitant activation of src by phosphorylation at Tyr416 (5-30 min) in alpha1-integrin immunoprecipitates containing the integrin binding proteins talin and paxillin, as well as the phoshorylated and activated forms of focal adhesion kinase (FAK) at Tyr397 (a FAK kinase activation signal), Tyr576 and Tyr861. This was associated with the lateral redistribution of alpha1-integrins in focal aggregates and persistent activation of the p130Cas/JNK pathways at 5-30 min, with the subsequent induction and activation of the matrix metalloproteinases MMP-2 and MMP-9 (2-12 h). These activated molecular scaffolds and signaling cascades were not observed in immunoprecipitates of alpha2- and beta1-integrins, and tetraspanin CD9, an invasion and metastasis suppressor linked to integrins and FAK signaling. Our data demonstrate that the lateral redistribution and clustering of alpha1-integrins results in the recruitment of the FAK/src motility-promoting signaling complex involved in cancer cell invasion. Disruption of this proinvasive pathway was accomplished by the dominant negative mutant of src (K295R, kinase dead), src pharmacological inhibitor (PP1) and alpha1-integrin function blocking antibodies. These findings support the notion that the alpha1-integrin- and src-dependent signalosome is a relevant therapeutic target against tumor progression in colon cancer patients.

  3. miR-199a-5p regulates β1 integrin through Ets-1 to suppress invasion in breast cancer. (United States)

    Li, Wentong; Wang, Hui; Zhang, Jinbao; Zhai, Limin; Chen, Weijuan; Zhao, Chunling


    Increasing evidence has revealed that miR-199a-5p is actively involved in tumor invasion and metastasis as well as in the decline of breast cancer tissues. In this research, overexpression of miR-199a-5p weakened motility and invasion of breast cancer cells MCF-7 and MDA-MB-231. Upregulation of Ets-1 increased breast cancer cell invasion, but the mechanism by which miR-199a-5p modulates activation of Ets-1 in breast cancer was not clarified. We investigated the relationship between miR-199a-5p and Ets-1 on the basis of 158 primary breast cancer case specimens, and the results showed that Ets-1 expression was inversely correlated with endogenous miR-199a-5p. Overexpression of miR-199a-5p reduced the mRNA and protein levels of Ets-1 in MCF-7 and MDA-MB-231 cells, whereas anti-miR-199a-5p elevated Ets-1. siRNA-mediated Ets-1 knockdown phenocopied the inhibition invasion of miR-199a-5p in vitro. Moreover, luciferase reporter assay revealed that miR-199a-5p directly targeted 3'-UTR of Ets-1 mRNA. This research revealed that miR-199a-5p could descend the levels of β1 integrin by targeting 3'-UTR of Ets-1 to alleviate the invasion of breast cancer via FAK/Src/Akt/mTOR signaling pathway. Our results provide insight into the regulation of β1 integrin through miR-199a-5p-mediated Ets-1 silence and will help in designing new therapeutic strategies to inhibit signal pathways induced by miR-199a-5p in breast cancer invasion.

  4. The α7β1-integrin accelerates fiber hypertrophy and myogenesis following a single bout of eccentric exercise. (United States)

    Lueders, Tara N; Zou, Kai; Huntsman, Heather D; Meador, Benjamin; Mahmassani, Ziad; Abel, Megan; Valero, M Carmen; Huey, Kimberly A; Boppart, Marni D


    The α(7)β(1)-integrin is a heterodimeric transmembrane protein that adheres to laminin in the extracellular matrix, representing a critical link that maintains structure in skeletal muscle. In addition to preventing exercise-induced skeletal muscle injury, the α(7)-integrin has been proposed to act as an intrinsic mechanosensor, initiating cellular growth in response to mechanical strain. The purpose of this study was to determine the extent to which the α(7)-integrin regulates muscle hypertrophy following eccentric exercise. Wild-type (WT) and α(7)-integrin transgenic (α(7)Tg) mice completed a single bout of downhill running exercise (-20°, 17 m/min, 60 min), and gastrocnemius-soleus complexes were collected 1, 2, 4, and 7 days (D) postexercise (PE). Maximal isometric force was maintained and macrophage accumulation was suppressed in α(7)Tg muscle 1D PE. Mean fiber cross-sectional area was unaltered in WT mice but increased 40% in α(7)Tg mice 7D PE. In addition, a rapid and striking fivefold increase in embryonic myosin heavy chain-positive fibers appeared in α(7)Tg mice 2D PE. Although Pax7-positive satellite cells were increased in α(7)Tg muscle 1D PE, the number of nuclei per myofiber was not altered 7D PE. Phosphorylation of mammalian target of rapamycin (mTOR) was significantly elevated in α(7)Tg 1D PE. This study provides the first demonstration that the presence of the α(7)β(1)-integrin in skeletal muscle increases fiber hypertrophy and new fiber synthesis in the early time course following a single bout of eccentric exercise. Further studies are necessary to elucidate the precise mechanism by which the α(7)-integrin can enhance muscle hypertrophy following exercise.

  5. Prostate Problems (United States)

    ... know the exact cause of your prostate problem. Prostatitis The cause of prostatitis depends on whether you ... prostate problem in men older than age 50. Prostatitis If you have a UTI, you may be ...

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

    LENUS (Irish Health Repository)

    Wang, Jiang Huai


    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.

  7. Loss of the α2β1 integrin alters human papilloma virus-induced squamous carcinoma progression in vivo and in vitro.

    Directory of Open Access Journals (Sweden)

    Thuy Tran

    Full Text Available Expression of the α2β1 integrin, a receptor for collagens and laminin, is altered during tumor progression. Recent studies have linked polymorphisms in the α2 integrin gene with oral, squamous cell carcinoma (SCC. To determine the α2β1 integrin's role in SCC progression, we crossed α2-null mice with K14-HPV16 transgenic animals. Pathological progression to invasive carcinoma was evaluated in HPV-positive, α2-null (HPV/KO and HPV-positive, wild-type (HPV/WT animals. α2β1 integrin expression stimulated progression from hyperplasia and papillomatosis to dysplasia with concomitant dermal mast cell infiltration. Moreover, lymph node metastasis was decreased by 31.3% in HPV/KO, compared to HPV/WT, animals. To evaluate the integrin-specific impact on the malignant epithelium versus the microenvironment, we developed primary tumor cell lines. Although transition from dysplasia to carcinoma was unaltered during spontaneous tumor development, isolated primary HPV/KO SCC cell lines demonstrated decreased migration and invasion, compared to HPV/WT cells. When HPV/WT and HPV/KO SCC cells were orthotopically injected into WT or KO hosts, tumor α2β1 integrin expression resulted in decreased tumor latency, regardless of host integrin status. HPV/WT SCC lines failed to demonstrate a proliferative advantage in vitro, however, the HPV/WT tumors demonstrated increased growth compared to HPV/KO SCC lines in vivo. Although contributions of the integrin to the microenvironment cannot be excluded, our studies indicate that α2β1 integrin expression by HPV-transformed keratinocytes modulates SCC growth and progression.

  8. Bone Regeneration using an Alpha 2 Beta 1 Integrin-Specific Hydrogel as a BMP-2 Delivery Vehicle (United States)

    Shekaran, Asha; García, José R.; Clark, Amy Y.; Kavanaugh, Taylor E.; Lin, Angela S.; Guldberg, Robert E.; García, Andrés J.


    Non-healing bone defects present tremendous socioeconomic costs. Although successful in some clinical settings, bone morphogenetic protein (BMP) therapies require supraphysiological dose delivery for bone repair, raising treatment costs and risks of complications. We engineered a protease-degradable poly(ethylene glycol) (PEG) synthetic hydrogel functionalized with a triple helical, α2β1 integrin-specific peptide (GFOGER) as a BMP-2 delivery vehicle. GFOGER-functionalized hydrogels lacking BMP-2 directed human stem cell differentiation and produced significant enhancements in bone repair within a critical-sized bone defect compared to RGD hydrogels or empty defects. GFOGER functionalization was crucial to the BMP-2-dependent healing response. Importantly, these engineered hydrogels outperformed the current clinical carrier in repairing non-healing bone defects at low BMP-2 doses. GFOGER hydrogels provided sustained in vivo release of encapsulated BMP-2, increased osteoprogenitor localization in the defect site, enhanced bone formation and induced defect bridging and mechanically robust healing at low BMP-2 doses which stimulated almost no bone regeneration when delivered from collagen sponges. These findings demonstrate that GFOGER hydrogels promote bone regeneration in challenging defects with low delivered BMP-2 doses and represent an effective delivery vehicle for protein therapeutics with translational potential. PMID:24726536

  9. NG2 Proteoglycan Promotes Endothelial Cell Motility and Angiogenesis via Engagement of Galectin-3 and α3β1 Integrin (United States)

    Fukushi, Jun-ichi; Makagiansar, Irwan T.; Stallcup, William B.


    The NG2 proteoglycan is expressed by microvascular pericytes in newly formed blood vessels. We have used in vitro and in vivo models to investigate the role of NG2 in cross-talk between pericytes and endothelial cells (EC). Binding of soluble NG2 to the EC surface induces cell motility and multicellular network formation in vitro and stimulates corneal angiogenesis in vivo. Biochemical data demonstrate the involvement of both galectin-3 and α3β1 integrin in the EC response to NG2 and show that NG2, galectin-3, and α3β1 form a complex on the cell surface. Transmembrane signaling via α3β1 is responsible for EC motility and morphogenesis in this system. Galectin-3–dependent oligomerization may potentiate NG2-mediated activation of α3β1. In conjunction with recent studies demonstrating the early involvement of pericytes in angiogenesis, these data suggest that pericyte-derived NG2 is an important factor in promoting EC migration and morphogenesis during the early stages of neovascularization. PMID:15181153

  10. Bone marrow-derived mesenchymal stem cells enhance angiogenesis via their α6β1 integrin receptor. (United States)

    Carrion, Bita; Kong, Yen P; Kaigler, Darnell; Putnam, Andrew J


    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.

  11. Proteomic analysis of α4β1 integrin adhesion complexes reveals α-subunit-dependent protein recruitment (United States)

    Byron, Adam; Humphries, Jonathan D; Craig, Sue E; Knight, David; Humphries, Martin J


    Integrin adhesion receptors mediate cell–cell and cell–extracellular matrix interactions, which control cell morphology and migration, differentiation, and tissue integrity. Integrins recruit multimolecular adhesion complexes to their cytoplasmic domains, which provide structural and mechanosensitive signaling connections between the extracellular and intracellular milieux. The different functions of specific integrin heterodimers, such as α4β1 and α5β1, have been attributed to distinct signal transduction mechanisms that are initiated by selective recruitment of adhesion complex components to integrin cytoplasmic tails. Here, we report the isolation of ligand-induced adhesion complexes associated with wild-type α4β1 integrin, an activated α4β1 variant in the absence of the α cytoplasmic domain (X4C0), and a chimeric α4β1 variant with α5 leg and cytoplasmic domains (α4Pα5L), and the cataloguing of their proteomes by MS. Using hierarchical clustering and interaction network analyses, we detail the differential recruitment of proteins and highlight enrichment patterns of proteins to distinct adhesion complexes. We identify previously unreported components of integrin adhesion complexes and observe receptor-specific enrichment of molecules with previously reported links to cell migration and cell signaling processes. Furthermore, we demonstrate colocalization of MYO18A with active integrin in migrating cells. These datasets provide a resource for future studies of integrin receptor-specific signaling events. PMID:22623428

  12. Prostate Ultrasound

    Medline Plus

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

  13. Prostate Ultrasound (United States)

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

  14. Neutrophil elastase cleavage of the gC1q domain impairs the EMILIN1-α4β1 integrin interaction, cell adhesion and anti-proliferative activity (United States)

    Maiorani, Orlando; Pivetta, Eliana; Capuano, Alessandra; Modica, Teresa Maria Elisa; Wassermann, Bruna; Bucciotti, Francesco; Colombatti, Alfonso; Doliana, Roberto; Spessotto, Paola


    The extracellular matrix glycoprotein EMILIN1 exerts a wide range of functions mainly associated with its gC1q domain. Besides providing functional significance for adhesion and migration, the direct interaction between α4β1 integrin and EMILIN1-gC1q regulates cell proliferation, transducing net anti-proliferative effects. We have previously demonstrated that EMILIN1 degradation by neutrophil elastase (NE) is a specific mechanism leading to the loss of functions disabling its regulatory properties. In this study we further analysed the proteolytic activity of NE, MMP-3, MMP-9, and MT1-MMP on EMILIN1 and found that MMP-3 and MT1-MMP partially cleaved EMILIN1 but without affecting the functional properties associated with the gC1q domain, whereas NE was able to fully impair the interaction of gC1q with the α4β1 integrin by cleaving this domain outside of the E933 integrin binding site. By a site direct mutagenesis approach we mapped the bond between S913 and R914 residues and selected the NE-resistant R914W mutant still able to interact with the α4β1 integrin after NE treatment. Functional studies showed that NE impaired the EMILIN1-α4β1 integrin interaction by cleaving the gC1q domain in a region crucial for its proper structural conformation, paving the way to better understand NE effects on EMILIN1-cell interaction in pathological context. PMID:28074935

  15. Interaction between {alpha}5{beta}1 integrin and secreted fibronectin is involved in macrophage differentiation of human HL-60 myeloid leukemia cells.

    Energy Technology Data Exchange (ETDEWEB)

    Laouar, A.; Collart, F. R.; Chubb, C. B. H.; Xie, B.; Huberman, E.; Center for Mechanistic Biology and Biotechnology; anl-cmb


    We examined the role of fibronectin (FN) and FN-binding integrins in macrophage differentiation. Increased FN and {alpha}5{beta}1 integrin gene expression was observed in phorbol 12-myristate 13-acetate PMA-treated HL-60 cells and PMA- or macrophage-CSF-treated blood monocytes before the manifestation of macrophage markers. After treatment of HL-60 cells and monocytes, newly synthesized FN was released and deposited on the dishes. An HL-60 cell variant, HL-525, which is deficient in the protein kinase C{beta} (PKC-{beta}) and resistant to PMA-induced differentiation, failed to express FN after PMA treatment. Transfecting HL-525 cells with a PKC-{beta} expression plasmid restored PMA-induced FN gene expression and macrophage differentiation. Untreated HL-525 cells (which have a high level of the {alpha}5{beta}1 integrin) incubated on FN differentiated into macrophages. The percentage of cells having a macrophage phenotype induced by PMA in HL-60 cells, by FN in HL-525 cells, or by either PMA or macrophage-CSF in monocytes was reduced in the presence of mAbs to FN and {alpha}5{beta}1 integrin. The integrin-signaling nonreceptor tyrosine kinase, p72{sup Syk}, was activated in PMA-treated HL-60 and FN-treated HL-525 cells. We suggest that macrophage differentiation involves the activation of PKC-{beta} and expression of extracellular matrix proteins such as FN and the corresponding integrins, {alpha}5{beta}1 integrin in particular. The stimulated cells, through the integrins, attach to substrates by binding to the deposited FN. This attachment, in turn, may through integrin signaling activate nonreceptor tyrosine kinases, including p72{sup Syk}, and later lead to expression of other genes involved in evoking the macrophage phenotype.

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

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    Annika Sommerfeld


    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.

  17. Alternagin-C, a disintegrin-like protein from the venom of Bothrops alternatus, modulates a2ß1 integrin-mediated cell adhesion, migration and proliferation

    Directory of Open Access Journals (Sweden)

    Selistre-de-Araujo H.S.


    Full Text Available The alpha2ß1 integrin is a major collagen receptor that plays an essential role in the adhesion of normal and tumor cells to the extracellular matrix. Alternagin-C (ALT-C, a disintegrin-like protein purified from the venom of the Brazilian snake Bothrops alternatus, competitively interacts with the alpha2ß1 integrin, thereby inhibiting collagen binding. When immobilized in plate wells, ALT-C supports the adhesion of fibroblasts as well as of human vein endothelial cells (HUVEC and does not detach cells previously bound to collagen I. ALT-C is a strong inducer of HUVEC proliferation in vitro. Gene expression analysis was done using an Affimetrix HU-95A probe array with probe sets of ~10,000 human genes. In human fibroblasts growing on collagen-coated plates, ALT-C up-regulates the expression of several growth factors including vascular endothelial growth factor, as well as some cell cycle control genes. Up-regulation of the vascular endothelial growth factor gene and other growth factors could explain the positive effect on HUVEC proliferation. ALT-C also strongly activates protein kinase B phosphorylation, a signaling event involved in endothelial cell survival and angiogenesis. In human neutrophils, ALT-C has a potent chemotactic effect modulated by the intracellular signaling cascade characteristic of integrin-activated pathways. Thus, ALT-C acts as a survival factor, promoting adhesion, migration and endothelial cell proliferation after binding to alpha2ß1 integrin on the cell surface. The biological activities of ALT-C may be helpful as a therapeutic strategy in tissue regeneration as well as in the design of new therapeutic agents targeting alpha2ß1 integrin.


    Furmento, Verónica A.; Marino, Julieta; Blank, Viviana C.; Cayrol, María Florencia; Cremaschi, Graciela A.; Aguilar, Rubén C.; Roguin, Leonor P.


    Multiple cytokines and growth factors expressed at the fetal-maternal interface are involved in the regulation of trophoblast functions and placental growth, but the role of G-CSF has not been completely established. Based on our previous study showing that G-CSF increases the activity of matrix metalloproteinase-2 and the release of vascular endothelial growth factor in Swan 71 human trophoblast cells, in this work we explore the possible contribution of G-CSF to cell migration and the G-CSF-triggered signaling pathway. We found that G-CSF induced morphological changes on actin cytoskeleton consistent with a migratory cell phenotype. G-CSF also up-regulated the expression levels of β1 integrin and promoted Swan 71 cell migration. By using selective pharmacological inhibitors and dominant negative mutants we showed that PI3K, Erk 1/2 and p38 pathways are required for promoting Swan 71 cell motility. It was also demonstrated that PI3K behaved as an upstream regulator of Erk 1/2 and p38 MAPK. In addition, the increase of β1 integrin expression was dependent on PI3K activation. In conclusion, our results indicate that G-CSF stimulates β1 integrin expression and Swan 71 cell migration by activating PI3K and MAPK signaling pathways, suggesting that G-CSF should be considered as an additional regulatory factor that contributes to a successful embryo implantation and to the placenta development. PMID:26992288

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

    Energy Technology Data Exchange (ETDEWEB)

    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: [Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109 (United States)


    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.

  20. Definition of molecular determinants of prostate cancer cell bone extravasation. (United States)

    Barthel, Steven R; Hays, Danielle L; Yazawa, Erika M; Opperman, Matthew; Walley, Kempland C; Nimrichter, Leonardo; Burdick, Monica M; Gillard, Bryan M; Moser, Michael T; Pantel, Klaus; Foster, Barbara A; Pienta, Kenneth J; Dimitroff, Charles J


    Advanced prostate cancer commonly metastasizes to bone, but transit of malignant cells across the bone marrow endothelium (BMEC) remains a poorly understood step in metastasis. Prostate cancer cells roll on E-selectin(+) BMEC through E-selectin ligand-binding interactions under shear flow, and prostate cancer cells exhibit firm adhesion to BMEC via β1, β4, and αVβ3 integrins in static assays. However, whether these discrete prostate cancer cell-BMEC adhesive contacts culminate in cooperative, step-wise transendothelial migration into bone is not known. Here, we describe how metastatic prostate cancer cells breach BMEC monolayers in a step-wise fashion under physiologic hemodynamic flow. Prostate cancer cells tethered and rolled on BMEC and then firmly adhered to and traversed BMEC via sequential dependence on E-selectin ligands and β1 and αVβ3 integrins. Expression analysis in human metastatic prostate cancer tissue revealed that β1 was markedly upregulated compared with expression of other β subunits. Prostate cancer cell breaching was regulated by Rac1 and Rap1 GTPases and, notably, did not require exogenous chemokines as β1, αVβ3, Rac1, and Rap1 were constitutively active. In homing studies, prostate cancer cell trafficking to murine femurs was dependent on E-selectin ligand, β1 integrin, and Rac1. Moreover, eliminating E-selectin ligand-synthesizing α1,3 fucosyltransferases in transgenic adenoma of mouse prostate mice dramatically reduced prostate cancer incidence. These results unify the requirement for E-selectin ligands, α1,3 fucosyltransferases, β1 and αVβ3 integrins, and Rac/Rap1 GTPases in mediating prostate cancer cell homing and entry into bone and offer new insight into the role of α1,3 fucosylation in prostate cancer development.

  1. α2β1 integrin, GPVI receptor, and common FcRγ chain on mouse platelets mediate distinct responses to collagen in models of thrombosis.

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    Robin J Marjoram

    Full Text Available Platelets express the α2β1 integrin and the glycoprotein VI (GPVI/FcRγ complex, both collagen receptors. Understanding platelet-collagen receptor function has been enhanced through use of genetically modified mouse models. Previous studies of GPVI/FcRγ-mediated collagen-induced platelet activation were perfomed with mice in which the FcRγ subunit was genetically deleted (FcRγ-/- or the complex was depleted. The development of α2β1-/- and GPVI-/- mice permits side-by-side comparison to address contributions of these collagen receptors in vivo and in vitro.To understand the different roles played by the α2β1 integrin, the GPVI receptor or FcRγ subunit in collagen-stimulated hemostasis and thrombosis, we compared α2β1-/-, FcRγ-/-, and GPVI-/- mice in models of endothelial injury and intravascular thrombosis in vivo and their platelets in collagen-stimulated activation in vitro. We demonstrate that both the α2β1 integrin and the GPVI receptor, but not the FcRγ subunit influence carotid artery occlusion in vivo. In contrast, the GPVI receptor and the FcRγ chain, but not the α2β1 integrin, play similar roles in intravascular thrombosis in response to soluble Type I collagen. FcRγ-/- platelets showed less attenuation of tyrosine phosphorylation of several proteins including RhoGDI when compared to GPVI-/- and wild type platelets. The difference between FcRγ-/- and GPVI-/- platelet phosphotyrosine levels correlated with the in vivo thrombosis findings.Our data demonstrate that genetic deletion of GPVI receptor, FcRγ chain, or the α2β1 integrin changes the thrombotic potentials of these platelets to collagen dependent on the stimulus mechanism. The data suggest that the FcRγ chain may provide a dominant negative effect through modulating signaling pathways in platelets involving several tyrosine phosphorylated proteins such as RhoGDI. In addition, these findings suggest a more complex signaling network downstream of the platelet

  2. Junctional adhesion molecule (JAM)-B supports lymphocyte rolling and adhesion through interaction with alpha4beta1 integrin. (United States)

    Ludwig, Ralf J; Hardt, Katja; Hatting, Max; Bistrian, Roxana; Diehl, Sandra; Radeke, Heinfried H; Podda, Maurizio; Schön, Michael P; Kaufmann, Roland; Henschler, Reinhard; Pfeilschifter, Josef M; Santoso, Sentot; Boehncke, Wolf-Henning


    Junctional adhesion molecule-A (JAM-A), JAM-B and JAM-C have been implicated in leucocyte transmigration. As JAM-B binds to very late activation antigen (VLA)-4, a leucocyte integrin that contributes to rolling and firm adhesion of lymphocytes to endothelial cells through binding to vascular cell adhesion molecule (VCAM)-1, we hypothesized that JAM-B is also involved in leucocyte rolling and firm adhesion. To test this hypothesis, intravital microscopy of murine skin microvasculature was performed. Rolling interactions of murine leucocytes were significantly affected by blockade of JAM-B [which reduced rolling interactions from 9.1 +/- 2.6% to 3.2 +/- 1.2% (mean +/- standard deviation)]. To identify putative ligands, T lymphocytes were perfused over JAM-B-coated slides in a dynamic flow chamber system. JAM-B-dependent rolling and sticking interactions were observed at low shear stress [0.3 dyn/cm(2): 220 +/- 71 (mean +/- standard deviation) versus 165 +/- 88 rolling (P JAM-B- compared with baseline], but not at higher shear forces (1.0 dyn/cm(2)). As demonstrated by antibody blocking experiments, JAM-B-mediated rolling and sticking of T lymphocytes was dependent on alpha4 and beta1 integrin, but not JAM-C expression. To investigate whether JAM-B-mediated leucocyte-endothelium interactions are involved in a disease-relevant in vivo model, adoptive transfer experiments in 2,4,-dinitrofluorobenzene (DNFB)-induced contact hypersensitivity reactions were performed in mice in the absence or in the presence of a function-blocking JAM-B antibody. In this model, JAM-B blockade during the sensitization phase impaired the generation of the immune response to DNFB, which was assessed as the increase in ear swelling in untreated, DNFB-challenged mice, by close to 40% [P = 0.037; analysis of variance (anova)]. Overall, JAM-B appears to contribute to leucocyte extravasation by facilitating not only transmigration but also rolling and adhesion.

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

    Energy Technology Data Exchange (ETDEWEB)

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


    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.

  4. Isolation of a germ-tube-forming revertant from Candida albicans B311V6.


    Buckley, H R; Daneo-Moore, L; Ahrens, J C; Sobel, J D


    We describe and partially characterize the isolation of a germ-tube-positive revertant from Candida albicans B311V6. This revertant has all of the properties of a germ-tube-forming strain of C. albicans except that it appears to have a nutrition defect.

  5. Adhesive stripping to remove epidermis in junctional epidermolysis bullosa for revertant cell therapy

    NARCIS (Netherlands)

    Gostynski, A.; Deviaene, F. C. L.; Pasmooij, A. M. G.; Pas, H. H.; Jonkman, M. F.


    Background Replacing mutant skin in epidermolysis bullosa (EB) by epithelial sheets of transduced autologous keratinocytes is the essential surgical step of ex vivo gene therapy. The same applies for revertant cell therapy in which epithelial sheets of revertant autologous keratinocytes are used. Re

  6. In vitro study of intracellular IL-1beta production and beta1 integrins expression in stimulated chondrocytes--effect of rhein. (United States)

    Gigant-Huselstein, C; Dumas, D; Payan, E; Muller, S; Bensoussan, D; Netter, P; Stoltz, J F


    The purpose of the present study was to investigate the intracellular IL-1beta production and beta1 integrins (alpha4/beta1 and alpha5/beta1) expression on chondrocytes. Chondroytes monolayer (human chondrosarcoma cell line HEM-C55) were incubated for 12, 24 and 48 hours in the presence of Tumor Necrosis Factor-alpha (TNF-alpha, Sigma, France) or recombinant human IL-1alpha (rh-IL1alpha, Becton Dickinson, France). After direct immunolabelling, cells were either analyzed on FACScan flow cytometer (Becton Dickinson, France), or observed under an epi-fluorescence inverted microscope equipped with the CellScan EPR optical scanning acquisition system (IPLab-Scanalytics, USA). We found that the IL-1beta mean fluorescence intensity in flow cytometry and in 3D microscopy was increased in the presence of TNF-alpha or rh-IL-1alpha, and alpha4/beta1 or alpha5/beta1 expression was higher on stimulated cells than on control cells. On the other hand, we have evaluated the in vitro effects of rhein (10(-5) M, Negma, France), an active metabolite of diacerein, on the intracellular IL-1beta and beta1 integrins expressed by stimulated or no-stimulated chondrocytes. The results indicated that rhein leads to a reduction of IL-1beta synthesis whereas a weak decrease of beta1 integrins receptors expression is observed. From this study, it seems that rhein partially reduce cytokine-induced intracellular IL-1beta production, and it has a weak action on alpha4/beta1 or alpha5/beta1 receptors.

  7. The role of alpha3beta1 integrin in determining the supramolecular organization of laminin-5 in the extracellular matrix of keratinocytes. (United States)

    deHart, Gregory W; Healy, Kevin E; Jones, Jonathan C R


    Analyses of mice with targeted deletions in the genes for alpha3 and beta1 integrin suggest that the alpha3beta1 integrin heterodimer likely determines the organization of the extracellular matrix within the basement membrane of skin. Here we tested this hypothesis using keratinocytes derived from alpha3 integrin-null mice. We have compared the organizational state of laminin-5, a ligand of alpha3beta1 integrin, in the matrix of wild-type keratinocytes with that of laminin-5 in the matrix of alpha3 integrin-null cells. Laminin-5 distributes diffusely in arc structures in the matrix of wild-type mouse keratinocytes, whereas laminin-5 is organized into linear, spike-like arrays by the alpha3 integrin-null cells. The fact that alpha3 integrin-null cells are deficient in their ability to assemble a proper laminin-5 matrix is also shown by their failure to remodel laminin-5 when plated onto surfaces coated with purified laminin-5 protein. In sharp contrast, wild-type keratinocytes organize exogenously added laminin-5 into discrete ring-like organizations. These findings led us next to assess whether differences in laminin-5 organization in the matrix of the wild-type and alpha3 integrin-null cells impact cell behavior. Our results indicate that alpha3 integrin-null cells are more motile than their wild-type counterparts and leave extensive trails of laminin-5 over the surface on which they move. Moreover, HEK 293 cells migrate significantly more on the laminin-5-rich matrix derived from the alpha3 integrin-null cells than on the wild-type keratinocyte laminin-5 matrix. In addition, alpha3 integrin-null cells show low strength of adhesion to surfaces coated with purified laminin-5 compared to wild-type cells although both the wild type and the alpha3 integrin-null keratinocytes adhere equally strongly to laminin-5 that has been organized into arrays by other epithelial cells. These data suggest: (1) that alpha3beta1 integrin plays an important role in determining the

  8. Prostate Ultrasound

    Medline Plus

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

  9. Binding of Alphaherpesvirus Glycoprotein H to Surface α4β1-Integrins Activates Calcium-Signaling Pathways and Induces Phosphatidylserine Exposure on the Plasma Membrane (United States)

    Gramatica, Andrea; Herrmann, Andreas; Osterrieder, Nikolaus


    ABSTRACT Intracellular signaling connected to integrin activation is known to induce cytoplasmic Ca2+ release, which in turn mediates a number of downstream signals. The cellular entry pathways of two closely related alphaherpesviruses, equine herpesviruses 1 and 4 (EHV-1 and EHV-4), are differentially regulated with respect to the requirement of interaction of glycoprotein H (gH) with α4β1-integrins. We show here that binding of EHV-1, but not EHV-4, to target cells resulted in a rapid and significant increase in cytosolic Ca2+ levels. EHV-1 expressing EHV-4 gH (gH4) in lieu of authentic gH1 failed to induce Ca2+ release, while EHV-4 with gH1 triggered significant Ca2+ release. Blocking the interaction between gH1 and α4β1-integrins, inhibiting phospholipase C (PLC) activation, or blocking binding of inositol 1,4,5-triphosphate (IP3) to its receptor on the endoplasmic reticulum (ER) abrogated Ca2+ release. Interestingly, phosphatidylserine (PS) was exposed on the plasma membrane in response to cytosolic calcium increase after EHV-1 binding through a scramblase-dependent mechanism. Inhibition of both Ca2+ release from the ER and scramblase activation blocked PS scrambling and redirected virus entry to the endocytic pathway, indicating that PS may play a role in facilitating virus entry directly at the plasma membrane. PMID:26489864

  10. 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

    Energy Technology Data Exchange (ETDEWEB)

    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


    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.

  11. Lunasin potentiates the effect of oxaliplatin preventing outgrowth of colon cancer metastasis, binds to α5β1 integrin and suppresses FAK/ERK/NF-κB signaling. (United States)

    Dia, Vermont P; Gonzalez de Mejia, Elvira


    The effect of lunasin on colon cancer metastasis was studied using three human colon cancer cell lines in vitro and a liver metastasis model of colon cancer in vivo. Lunasin bound with α5β1 integrin and internalized into the nucleus of KM12L4 human colon cancer cells. Lunasin (10 μM) inhibited the activation of focal adhesion kinase (FAK) by 28%, 39% and 60% in RKO, HCT-116 and KM12L4 human colon cancer cells, respectively. Lunasin caused an increase in the expression of the inhibitor of kappa B alpha (IκB-α), a decrease in nuclear p50 NF-κB and a reduction in the migration of cancer cells. Lunasin (4 mg/kg bw) inhibited metastasis and potentiated the effect of oxaliplatin by reducing the expression of proliferating cell nuclear antigen. Liver metastatic nodules were reduced from 28 (PBS) to 14 (lunasin, P = 0.047) while combination of lunasin and oxaliplatin to 5 (P = 0.004). The tumor burden was reduced from 0.13 (PBS) to 0.10 (lunasin, P = 0.039) to 0.04 (lunasin + oxaliplatin, P cancer cells by direct binding with α5β1 integrin suppressing FAK/ERK/NF-κB signaling, and potentiated the effect of oxaliplatin in preventing the outgrowth of metastasis.

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

    Directory of Open Access Journals (Sweden)

    Ohannessian Arthur


    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Abreu, Hamilton F.G., E-mail: [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: [Universidade Federal do Ceará, Campus do Pici-Bloco 729, CEP 60440-554 Fortaleza, CE (Brazil)


    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.

  14. Prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

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


    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.

  15. Discoidin domain receptors promote α1β1- and α2β1-integrin mediated cell adhesion to collagen by enhancing integrin activation.

    Directory of Open Access Journals (Sweden)

    Huifang Xu

    Full Text Available The discoidin domain receptors, DDR1 and DDR2, are receptor tyrosine kinases that bind to and are activated by collagens. Similar to collagen-binding β1 integrins, the DDRs bind to specific motifs within the collagen triple helix. However, these two types of collagen receptors recognize distinct collagen sequences. While GVMGFO (O is hydroxyproline functions as a major DDR binding motif in fibrillar collagens, integrins bind to sequences containing Gxx'GEx". The DDRs are thought to regulate cell adhesion, but their roles have hitherto only been studied indirectly. In this study we used synthetic triple-helical collagen-derived peptides that incorporate either the DDR-selective GVMGFO motif or integrin-selective motifs, such as GxOGER and GLOGEN, in order to selectively target either type of receptor and resolve their contributions to cell adhesion. Our data using HEK293 cells show that while cell adhesion to collagen I was completely inhibited by anti-integrin blocking antibodies, the DDRs could mediate cell attachment to the GVMGFO motif in an integrin-independent manner. Cell binding to GVMGFO was independent of DDR receptor signalling and occurred with limited cell spreading, indicating that the DDRs do not mediate firm adhesion. However, blocking the interaction of DDR-expressing cells with collagen I via the GVMGFO site diminished cell adhesion, suggesting that the DDRs positively modulate integrin-mediated cell adhesion. Indeed, overexpression of the DDRs or activation of the DDRs by the GVMGFO ligand promoted α1β1 and α2β1 integrin-mediated cell adhesion to medium- and low-affinity integrin ligands without regulating the cell surface expression levels of α1β1 or α2β1. Our data thus demonstrate an adhesion-promoting role of the DDRs, whereby overexpression and/or activation of the DDRs leads to enhanced integrin-mediated cell adhesion as a result of higher integrin activation state.

  16. 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

    Directory of Open Access Journals (Sweden)

    Maria Elisa Manetti


    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.

  17. Beta-1 integrin-mediated adhesion may be initiated by multiple incomplete bonds, thus accounting for the functional importance of receptor clustering. (United States)

    Vitte, Joana; Benoliel, Anne-Marie; Eymeric, Philippe; Bongrand, Pierre; Pierres, Anne


    The regulation of cell integrin receptors involves modulation of membrane expression, shift between different affinity states, and topographical redistribution on the cell membrane. Here we attempted to assess quantitatively the functional importance of receptor clustering. We studied beta-1 integrin-mediated attachment of THP-1 cells to fibronectin-coated surfaces under low shear flow. Cells displayed multiple binding events with a half-life of the order of 1 s. The duration of binding events after the first second after arrest was quantitatively accounted for by a model assuming the existence of a short-time intermediate binding state with 3.6 s(-1) dissociation rate and 1.3 s(-1) transition frequency toward a more stable state. Cell binding to surfaces coated with lower fibronectin densities was concluded to be mediated by single molecular interactions, whereas multiple bonds were formed intermediate state. Receptor aggregation was induced by treating cells with neutral antiintegrin antibody and antiimmunoglobulin antibodies. A semiquantitative confocal microscopy study suggested that this treatment increased between 40% and 100% the average number of integrin receptors located in a volume of approximately 0.045 microm(3) surrounding each integrin. This aggregation induced up to 2.7-fold increase of the average number of bonds. Flow cytometric analysis of fluorescent ligand binding showed that THP-1 cells displayed low-affinity beta-1 integrins with a dissociation constant in the micromolar range. It is concluded that the initial step of cell adhesion was mediated by multiple incomplete bonds rather than a single equilibrium-state ligand receptor association. This interpretation accounts for the functional importance of integrin clustering.

  18. 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

    DEFF Research Database (Denmark)

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


    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...

  19. Prostatitis - nonbacterial (United States)

    NBP; Prostatodynia; Pelvic pain syndrome; CPPS; Chronic nonbacterial prostatitis; Chronic genitourinary pain ... Possible causes of nonbacterial prostatitis include: A past ... common types of bacteria Irritation caused by a backup of urine ...

  20. Prostate Ultrasound

    Medline Plus

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

  1. Prostate Ultrasound

    Medline Plus

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

  2. Prostate Cancer (United States)

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

  3. Chronic prostatitis


    Le, Brian; Schaeffer, Anthony J.


    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.

  4. Chronic prostatitis


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


    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.

  5. Enlarged prostate (United States)

    ... prostate URL of this page: // Enlarged prostate To use the sharing ... sperm during ejaculation. The prostate gland surrounds the urethra, the tube ... hyperplasia (BPH). It is not cancer, and it does not raise your risk for ...

  6. Carbon nanotube-based substrates promote cardiogenesis in brown adipose-derived stem cells via β1-integrin-dependent TGF-β1 signaling pathway

    Directory of Open Access Journals (Sweden)

    Sun H


    Full Text Available Hongyu Sun,1,* Yongchao Mou,2,* Yi Li,3,* Xia Li,4,* Zi Chen,2 Kayla Duval,2 Zhu Huang,1 Ruiwu Dai,1 Lijun Tang,1 Fuzhou Tian1 1Department of General Surgery, Chengdu Military General Hospital, Chengdu, People’s Republic of China; 2Thayer School of Engineering, Dartmouth College, Hanover, NH, USA; 3Department of Cardiology, The General Hospital of Chinese People’s Armed Police Forces, Beijing, People’s Republic of China; 4Affiliated Hospital of Academy of Military Medical Sciences, Beijing, People’s Republic of China *These authors contributed equally to this work Abstract: Stem cell-based therapy remains one of the promising approaches for cardiac repair and regeneration. However, its applications are restricted by the limited efficacy of cardiac differentiation. To address this issue, we examined whether carbon nanotubes (CNTs would provide an instructive extracellular microenvironment to facilitate cardiogenesis in brown adipose-derived stem cells (BASCs and to elucidate the underlying signaling pathways. In this study, we systematically investigated a series of cellular responses of BASCs due to the incorporation of CNTs into collagen (CNT-Col substrates that promoted cell adhesion, spreading, and growth. Moreover, we found that CNT-Col substrates remarkably improved the efficiency of BASCs cardiogenesis by using fluorescence staining and quantitative real-time reverse transcription-polymerase chain reaction. Critically, CNTs in the substrates accelerated the maturation of BASCs-derived cardiomyocytes. Furthermore, the underlying mechanism for promotion of BASCs cardiac differentiation by CNTs was determined by immunostaining, quantitative real-time reverse transcription-polymerase chain reaction, and Western blotting assay. It is notable that β1-integrin-dependent TGF-β1 signaling pathway modulates the facilitative effect of CNTs in cardiac differentiation of BASCs. Therefore, it is an efficient approach to regulate cardiac

  7. Laminin isoforms and their integrin receptors in glioma cell migration and invasiveness: Evidence for a role of alpha5-laminin(s) and alpha3beta1 integrin. (United States)

    Kawataki, Tomoyuki; Yamane, Tetsu; Naganuma, Hirofumi; Rousselle, Patricia; Andurén, Ingegerd; Tryggvason, Karl; Patarroyo, Manuel


    Glioma cell infiltration of brain tissue often occurs along the basement membrane (BM) of blood vessels. In the present study we have investigated the role of laminins, major structural components of BMs and strong promoters of cell migration. Immunohistochemical studies of glioma tumor tissue demonstrated expression of alpha2-, alpha3-, alpha4- and alpha5-, but not alpha1-, laminins by the tumor vasculature. In functional assays, alpha3 (Lm-332/laminin-5)- and alpha5 (Lm-511/laminin-10)-laminins strongly promoted migration of all glioma cell lines tested. alpha1-Laminin (Lm-111/laminin-1) displayed lower activity, whereas alpha2 (Lm-211/laminin-2)- and alpha4 (Lm-411/laminin-8)-laminins were practically inactive. Global integrin phenotyping identified alpha3beta1 as the most abundant integrin in all the glioma cell lines, and this laminin-binding integrin exclusively or largely mediate the cell migration. Moreover, pretreatment of U251 glioma cells with blocking antibodies to alpha3beta1 integrin followed by intracerebral injection into nude mice inhibited invasion of the tumor cells into the brain tissue. The cell lines secreted Lm-211, Lm-411 and Lm-511, at different ratios. The results indicate that glioma cells secrete alpha2-, alpha4- and alpha5-laminins and that alpha3- and alpha5-laminins, found in brain vasculature, selectively promote glioma cell migration. They identify alpha3beta1 as the predominant integrin and laminin receptor in glioma cells, and as a brain invasion-mediating integrin.

  8. Neurite outgrowth on a fibronectin isoform expressed during peripheral nerve regeneration is mediated by the interaction of paxillin with α4β1 integrins

    Directory of Open Access Journals (Sweden)

    Ginsberg Mark H


    Full Text Available Abstract Background The regeneration of peripheral nerve is associated with a change in the alternative splicing of the fibronectin primary gene transcript to re-express embryonic isoforms containing a binding site for α4β1 integrins that promote neurite outgrowth. Here we use PC12 cells to examine the role of the interaction between paxillin and the α4 integrin cytoplasmic domain in neurite outgrowth. Results Expression of α4 with mutations in the paxillin-binding domain reduced neurite outgrowth on recombinant embryonic fibronectin fragments relative to wild type α4. Over-expression of paxillin promoted neurite outgrowth while a mutant isoform lacking the LD4 domain implicated in the regulation of ARF and Rac GTPases was less effective. Optimal α4-mediated migration in leucocytes requires spatial regulation of α4 phosphorylation at Ser988, a post-translational modification that blocks paxillin binding to the integrin cytoplasmic domain. In keeping with this α4(S988D, which mimics phosphorylated α4, did not promote neurite outgrowth. However, α4 was not phosphorylated in the PC12 cells, and a non-phosphorylatable α4(S988A mutant promoted neurite outgrowth indistinguishably from the wild type integrin. Conclusion We establish the importance of the α4 integrin-paxillin interaction in a model of axonal regeneration and highlight differing dependence on phosphorylation of α4 for extension of neuronal growth cones and migration of non-neural cells.

  9. Hsp70 stabilizes lysosomes and reverts Niemann-Pick disease-associated lysosomal pathology

    DEFF Research Database (Denmark)

    Kirkegaard, Thomas; Roth, Anke G; Petersen, Nikolaj H T


    inhibition of ASM, effectively revert the Hsp70-mediated stabilization of lysosomes. Notably, the reduced ASM activity in cells from patients with Niemann-Pick disease (NPD) A and B-severe lysosomal storage disorders caused by mutations in the sphingomyelin phosphodiesterase 1 gene (SMPD1) encoding for ASM...

  10. About Reverted Austenite in Carburized Layers of Low-Carbon Martensitic Steels (United States)

    Ivanov, A. S.; Bogdanova, M. V.; Vylezhnev, V. P.


    Processes of surface hardening in low-carbon martensitic steel 24Kh2G2NMFTB under carburizing and subsequent quenching from the intercritical temperature range are studied. Special features of formation of reverted austenite with high strength and stability are considered.

  11. Multiple correcting COL17A1 mutations in patients with revertant mosaicism of epidermolysis bullosa

    NARCIS (Netherlands)

    Pasmooij, AMG; Pas, HH; Deviaene, FCL; Nijenhuis, Albertine; Jonkman, MF


    Revertant mosaicism by somatic reversion of inherited mutations has been described for a number of genetic diseases. Several mechanisms can underlie this reversion process, such as gene conversion, crossing-over, true back mutation, and second-site mutation. Here, we report the occurrence of multipl

  12. Prostate Cancer


    Eggener, Scott


    Prostate cancer continues to be a significant public health issue worldwide, particularly in countries where men have life expectancies long enough to clinically manifest the disease. In many countries, it remains one of the leading causes of cancer-related morbidity and mortality.Although significant progress has been made over the past few decades, many elements regarding the diagnosis and management of patients with prostate cancer remain enigmatic. In this Prostate Cancer special issue, o...

  13. Apoptotic and anti-adhesion effect of ajoene, a garlic derived compound, on the murine melanoma B16F10 cells: possible role of caspase-3 and the alpha(4)beta(1) integrin. (United States)

    Ledezma, Eliades; Apitz-Castro, Rafael; Cardier, José


    In this study we evaluated the hypothesis that the antitumor activity of ajoene could be associated with its apoptosis-inducing effect, and with its ability to block the expression of the alpha(4)beta(1) integrin, in the murine melanoma B16F10 cells. Ajoene induced a significant reduction in B16F10 viability (IC(50)=62 microM), in a dose-dependent manner. Flow cytometric analysis showed that the cytotoxic effect of this compound was associated with caspase-3 activation. Ajoene at 25 microM altered the alpha(4)beta(1) integrin expression on B16F10, and induced a significant reduction in the adhesion of these cells to an endothelial cell monolayer.

  14. Prostate-specific membrane antigen (PSMA) assembles a macromolecular complex regulating growth and survival of prostate cancer cells "in vitro" and correlating with progression "in vivo". (United States)

    Perico, Maria Elisa; Grasso, Silvia; Brunelli, Matteo; Martignoni, Guido; Munari, Enrico; Moiso, Enrico; Fracasso, Giulio; Cestari, Tiziana; Naim, Hassan Y; Bronte, Vincenzo; Colombatti, Marco; Ramarli, Dunia


    The expression of Prostate Specific-Membrane Antigen (PSMA) increases in high-grade prostate carcinoma envisaging a role in growth and progression. We show here that clustering PSMA at LNCaP or PC3-PSMA cell membrane activates AKT and MAPK pathways thus promoting proliferation and survival. PSMA activity was dependent on the assembly of a macromolecular complex including filamin A, beta1 integrin, p130CAS, c-Src and EGFR. Within this complex beta1 integrin became activated thereby inducing a c-Src-dependent EGFR phosphorylation at Y1086 and Y1173 EGF-independent residues. Silencing or blocking experiments with drugs demonstrated that all the complex components were required for full PSMA-dependent promotion of cell growth and/or survival in 3D culture, but that p130CAS and EGFR exerted a major role. All PSMA complex components were found assembled in multiple samples of two high-grade prostate carcinomas and associated with EGFR phosphorylation at Y1086. The expression of p130CAS and pEGFRY1086 was thus analysed by tissue micro array in 16 castration-resistant prostate carcinomas selected from 309 carcinomas and stratified from GS 3+4 to GS 5+5. Patients with Gleason Score ≤5 resulted negative whereas those with GS≥5 expressed p130CAS and pEGFRY1086 in 75% and 60% of the cases, respectively.Collectively, our results demonstrate for the first time that PSMA recruits a functionally active complex which is present in high-grade patients. In addition, two components of this complex, p130CAS and the novel pEGFRY1086, correlate with progression in castration-resistant patients and could be therefore useful in therapeutic or surveillance strategies of these patients.


    Institute of Scientific and Technical Information of China (English)

    Hu Yaozhong; Long Hongwei


    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.

  16. La Spagna dell’età napoleonica nei romanzi storici di Arturo Pérez-Reverte

    Directory of Open Access Journals (Sweden)

    Luca Maramotti


    Full Text Available Four of the historical novels of Arturo Pérez-Reverte are set in the context of the Napoleonic era. The skilful descriptive ability of the author focus primarily on the military aspect: it is the character’s perspective, involved in war actions, which provides an interesting interpretation of the period, through a subjective evaluation which often departs from documentary work.

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

    Directory of Open Access Journals (Sweden)

    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.


    Directory of Open Access Journals (Sweden)

    D. Lesmono


    Full Text Available We study a stochastic differential equation (SDE describing a class of mean-reverting diffusions on a bounded interval. The drift coefficient is not continuous near theboundaries. Nor does it satisfy either of the usual Lipschitz or linear growth conditions.We characterize the boundary behaviour, identifying two possibilities: entrance boundaryand regular boundary. In the case of an entrance boundary we establish existence anduniqueness of the solution to the SDE.

  19. MRI of the Prostate (United States)

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

  20. Benign prostate hyperplasia (BPH) - resources (United States)

    Resources - benign prostatic hyperplasia (BPH); Prostate enlargement resources; BPH resources ... The following organizations provide information on benign prostatic hyperplasia ( prostate enlargement ... Urology Care Foundation -- www. ...

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

    Directory of Open Access Journals (Sweden)

    Jia Dongxuan


    Full Text Available Abstract Background 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. Methods 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. Results 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. Conclusions 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.

  2. Prostatic melanosis

    Directory of Open Access Journals (Sweden)

    Kemal DENİZ


    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

  3. Xanthogranulomatous Prostatitis, a Rare Prostatic Entity

    Directory of Open Access Journals (Sweden)

    Alejandro Noyola


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

  4. Xanthogranulomatous Prostatitis, a Rare Prostatic Entity. (United States)

    Noyola, Alejandro; Gil, José Fernando; Lujano, Heriberto; Piñon, Omar; Muñoz, Gabriel; Michel, José Manuel; Garcia, Jorge; Valdez, Jorge; Morales, Omar


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

  5. Prostate brachytherapy (United States)

    ... the prostate. The doctor may use a computerized robot to do this. The radioactive material is removed ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  6. Prostatitis - bacterial (United States)

    ... infection in or around the testicles ( epididymitis or orchitis ), you may also have symptoms of that condition. ... In: Wein AJ, ed. Prostatitis and related conditions, orchitis, and epididymitis. Campbell-Walsh Urology . 10th ed. Philadelphia, ...

  7. Prostate Cancer (United States)

    ... may help you cope with your distress, including: Art therapy Dance or movement therapy Exercise Meditation Music ... . Mayo Clinic Footer Legal Conditions and ...

  8. Prostate Ultrasound

    Medline Plus

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

  9. Prostate Ultrasound

    Medline Plus

    Full Text Available ... also known as benign prostatic hyperplasia (BPH) , with measurements acquired as needed for any treatment planning. detect ... Rarely, a small amount of blood may be present in the sperm or urine following the procedure. ...

  10. Prostate Ultrasound

    Medline Plus

    Full Text Available ... also known as benign prostatic hyperplasia (BPH) , with measurements acquired as needed for any treatment planning. detect ... accredited facilities database . This website does not provide cost information. The costs for specific medical imaging tests, ...

  11. Prostate cancer

    DEFF Research Database (Denmark)

    Chabanova, Elizaveta; Balslev, Ingegerd; Logager, Vibeke


    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....

  12. The expressiom of β1 integrin in colons of Hirschsprung disease%先天性肠无神经节细胞症中β1整联蛋白的表达

    Institute of Scientific and Technical Information of China (English)

    赵占波; 王秀良; 丁雄辉; 孙艳辉; 段文娟; 金鑫; 金先庆


    Objective To investigate the expression of β1 integrin (ITGB1) in the tissue samples from patients with Hirschsprung's disease (HD).Methods The stenotic,transitional and normal appearance intestines from forty patients with HD were collected during operation.For comparative gene expression studies,the expression levels of β1 integrin was detected using immunohistochemistry,Real-time PCR (RT-PCR) and western blotting.Results Immunohistochemistry studies shows that β1 integrin immunoprecipitation product was mainly localized to the cytoplasm and membrane of the ganglion cells.The mean optical density(OD) value was 0.86 ± 0.16,0.61 ± 0.15,and 0.35 ± 0.07 (give in descending order) in normal,transitional and stenotic segments of HD,respectively,the difference was statistically significant (P < 0.05).The mRNA expression of β1 integrin in stenotic and transitional segments was significantly lower than that in the normal bowel segment (the relative quantification was 0.77 ± 0.17,1.08 ± 0.15,2.26 ± 0.29,respectively,P<0.05).The protein expression profile of β1 integrin in these patients were similar to that of mRNA.Conclusions The expression of β1 integrin is decreased in the affected colon from the patients with HD,which may play a role in the pathogenesis of HD.%目的 探讨β1整联蛋白(integrin)在先天性肠无神经节细胞症(Hirsehsprung disease,HD)患儿不同肠段各层中有无变化及在HD发病中的可能作用.方法 取40例先天性肠无神经节细胞症患儿的痉挛段、移行段、正常段.采用免疫组织化学法染色、Western blot和RT-PCR检测肠壁中β1 integrin蛋白和mRNA的表达情况,并结合图像分析,比较表达的差异.结果 免疫组织化学结果示β1 integrin免疫沉淀产物主要表达在神经节细胞的胞质和胞膜中表达,正常对照组、移行段和痉挛段肠壁中阳性区域平均光密度值分别为0.86±0.16、0.61±0.15和0.35±0.07,呈依次递减,

  13. Monoclonal antibodies to human laminin α4 chain globular domain inhibit tumor cell adhesion and migration on laminins 411 and 421, and binding of α6β1 integrin and MCAM to α4-laminins. (United States)

    Ishikawa, Taichi; Wondimu, Zenebech; Oikawa, Yuko; Ingerpuu, Sulev; Virtanen, Ismo; Patarroyo, Manuel


    α4-Laminins, such as laminins 411 and 421, are mesenchymal laminins expressed by vascular and lymphatic endothelial cells, leukocytes and other normal cell types. These laminins are recognized by α6β1 and α6β4 integrins and MCAM (CD146), and promote adhesion and migration of the cells. α4-Laminins are also expressed and secreted by some tumor cells and strongly promote tumor cell migration. Moreover, the abluminal side of blood and/or lymphatic vessels and the nerve perineurium, common tracks of tumor cell dissemination, express α4-laminins, and these laminin isoforms, when expressed in the stroma, may contribute to tumor invasion. In the present study, we examined ten mAbs to human laminin α4 chain for their reactivity with the isolated laminin α4 globular domain, their ability to inhibit tumor cell adhesion and migration on laminins 411 and 421, and their effect on the binding of α6β1 integrin and MCAM to both α4-laminins. Most of the mAbs reacted with the laminin α4 globular domain, but only two, mAbs FC10 and 084, significantly inhibited tumor cell adhesion and migration on laminin-411. When used in combination, these antibodies practically abolished the cell adhesion and migration on laminin-411 and significantly reduced the cellular responses on laminin-421. Accordingly, mAbs FC10 and 084 significantly inhibited the binding of purified α6β1 integrin and MCAM to laminins 411 and 421. These results indicate that mAbs to the laminin α4 globular domain are able to inhibit tumor cell adhesion and migration on laminins 411 and 421, and that α6β1 integrin and MCAM bind α4-laminins at very close sites on the globular domain. These reagents contribute to a better understanding of the biology of α4-laminins and may have a therapeutic potential in malignant and inflammatory diseases.

  14. Inhibition on Apoptosis Induced by Elevated Hydrostatic Pressure in Retinal Ganglion Cell-5 via Laminin Upregulating β1-integrin/Focal Adhesion Kinase/Protein Kinase B Signaling Pathway

    Institute of Scientific and Technical Information of China (English)

    Yi Li; Yan-Ming Chen; Ming-Ming Sun; Xiao-Dan Guo; Ya-Chen Wang; Zhong-Zhi Zhang


    Background:Glaucoma is a progressive optic neuropathy characterized by degeneration of neurons due to loss of retinal ganglion cells (RGCs).High intraocular pressure (HIOP),the main risk factor,causes the optic nerve damage.However,the precise mechanism of HIOP-induced RGC death is not yet completely understood.This study was conducted to determine apoptosis of RGC-5 cells induced by elevated hydrostatic pressures,explore whether laminin is associated with apoptosis under pressure,whether laminin can protect RGCs from apoptosis and affirm the mechanism that regulates the process of RGCs survival.Methods:RGC-5 cells were exposed to 0,20,40,and 60 mmHg in a pressurized incubator for 6,12,and 24 h,respectively.The effect of elevated hydrostatic pressure on RGC-5 cells was measured by Annexin V-fluorescein isothiocyanate/propidium iodide staining,3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay,and Western blotting of cleaved caspase-3 protein.Location and expression oflaminin were detected by immunofluorescence.The expression of β 1-integrin,phosphorylation of focal adhesion kinase (FAK) and protein kinase B (PKB,or AKT) were investigated with real-time polymerase chain reaction and Western blotting analysis.Results:Elevated hydrostatic pressure induced apoptosis in cultured RGC-5 cells.Pressure with 40 mmHg for 24 h induced a maximum apoptosis.Laminin was declined in RGC-5 cells after exposing to 40 mmHg for 24 h.After pretreating with laminin,RGC-5 cells survived from elevated pressure.Furthermore,β1-integrin and phosphorylation of FAK and AKT were increased compared to 40 mmHg group.Conclusions:The data show apoptosis tendency of RGC-5 cells with elevated hydrostatic pressure.Laminin can protect RGC-5 cells against high pressure via β 1-integrin/FAK/AKT signaling pathway.These results suggest that the decreased laminin of RGC-5 cells might be responsible for apoptosis induced by elevated hydrostatic pressure,and laminin or activating β1

  15. 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

    Energy Technology Data Exchange (ETDEWEB)

    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)


    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

  16. Gray level entropy matrix is a superior predictor than multiplex ELISA in the detection of reactive stroma and metastatic potential of high-grade prostatic adenocarcinoma. (United States)

    Jia, Xiaopeng; Sun, Yanan; Wang, Baozhi


    Recent reports have indicated that not only the primary glandular tissue but also the surrounding stromal tissue plays an active role in the progression of carcinoma. Such is true for cancer tissues arising in the prostate. However, the precise role of stromal tissue in benign prostatic hyperplasia (BPH) and prostate adenocarcinoma is not well described. We undertook this current investigation to examine the changes in orientation of the extracellular matrix and correlate with prostatic cancer progression. We used a novel form of image analysis called gray level entropy matrix (GLEM) texture analysis to evaluate morphometric changes in stromal tissues. We used normal prostatic tissue obtained from cadaveric specimen and compared with BPH, prostatic intraepithelium neoplastic, hormone responsive prostatic adenocarcinoma and castration-resistant prostatic adenocarcinoma tissues. GLEM showed higher entropy in disease-resistant prostatic tissues, compared with benign forms of all spectra of pathologically diagnosed prostatic tissues (P entropy is reflective of the disorganized morphological organization of the stroma, possibly reflecting the reactive matrix. In contrast, ELISA revealed that although individually correlated with the progressive stages of benign and carcinomatous prostatic tissues and trend correlation between groups, intergroup comparisons failed to arrive at statistical significance of comparisons between markers of neovasculogenesis, vascular endothelial growth factor, epithelial-mesenchymal transition (beta1-integrin, E-cadherin, MMP3) and osteogenic metastasis (RANKL and osteoprotegerin). The results of our study demonstrate the potential of GLEM entropy of gray level pixel in providing quasiquantitative estimate of a reactive stroma in advance stages of prostatic adenocarcinoma and thus can be routinely used in clinical decision making.

  17. Prostatic paracoccidioidomycosis: differential diagnosis of prostate cancer

    Directory of Open Access Journals (Sweden)

    Daniel Lima Lopes


    Full Text Available Symptomatic prostatic paracoccidioidomycosis (PCM is a very rare condition; however, it may express as a typical benign prostatic hyperplasia or a simulating prostatic adenocarcinoma. This case report presents PCM mimicking prostatic adenocarcinoma. The purpose of this paper is to call the general physician's attention to this important differential diagnosis.

  18. Formation and Growth Kinetics of Reverted Austenite During Tempering of a High Co-Ni Steel (United States)

    Gruber, Marina; Ressel, Gerald; Méndez Martín, Francisca; Ploberger, Sarah; Marsoner, Stefan; Ebner, Reinhold


    It is well known that high Co-Ni steels exhibit excellent toughness. Since the good toughness in these steels is supposed to be related to thin layers of austenite between martensite crystals, this work presents an experimental study corroborated with diffusional calculations to characterize the evolution of reverted austenite. Atom probe measurements were conducted for analyzing the element distribution in austenite and martensite during tempering. These results were correlated with crystallographic information, which was obtained by using transmission electron microscopy investigations. Additionally, the experimental findings were compared with kinetic calculations with DICTRA™. The investigations reveal that reverted austenite formation during tempering is connected with a redistribution of Ni, Co, Cr, and Mo atoms. The austenite undergoes a Ni and Cr enrichment and a Co depletion, while in the neighboring martensite, a zone of Ni and Cr depletion and Co enrichment is formed. The changes in the chemical composition of austenite during tempering affect the stability of the austenite against phase transformation to martensite during plastic deformation and have thus decisive influence on the toughness of the material.

  19. Mononuclear cell therapy reverts cuff-induced thrombosis in apolipoprotein E-deficient mice

    Directory of Open Access Journals (Sweden)

    Lima Leandro C F


    Full Text Available Abstract Background Stem/progenitor cell-based therapy has successfully been used as a novel therapeutic strategy for vascular diseases triggered by endothelial dysfunction. The aim of this study was to investigate the effects of mononuclear cell (MNC therapy in situ on carotid cuff-induced occlusive thrombus in the apolipoprotein E knockout (apoE-/- mouse. Methods Spleen-derived MNCs were isolated from green fluorescent protein (GFP-transgenic mice for cell treatment. A cuff-induced thrombus model was produced by placing a nonconstrictive silastic collar around the left common carotid artery in 20-week-old female apoE-/- mice. After 10 days, the cuff was removed, and the animals received in situ MNCs (Cuff-MNC or vehicle (Cuff-Vehicle and were compared with sham-operated animals (Sham. Results The histological analysis showed that the MNC treatment reverted occlusive thrombus formation compared to the vehicle and the vessel lumen area to that observed in the Sham group (MNC, 50 ± 4; Vehicle, 20 ± 4; Sham, 55 ± 2 x103 μm2; p -/- mice. Conclusion In situ short-term MNC therapy was able to revert cuff-induced occlusive thrombi in the carotid arteries of apoE-/- mice, possibly through the homing of EPCs, reduction of oxidative stress and decreased apoptosis.

  20. A completely calcified prostate

    Directory of Open Access Journals (Sweden)

    Vinod Priyadarshi


    Full Text Available Prostatic calcification and prostatic calculus formation is commonly seen in adult population with chronic prostatitis, however, gross prostatic calcification which involves more than 3 cm2 of the gland is quite rare. We are presenting here one such case in which almost whole glandular prostate was converted into stone which is never reported so far.

  1. 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. (United States)

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


    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.

  2. Revertant fibers in the mdx murine model of Duchenne muscular dystrophy: an age- and muscle-related reappraisal.

    Directory of Open Access Journals (Sweden)

    Sarah R Pigozzo

    Full Text Available Muscles in Duchenne dystrophy patients are characterized by the absence of dystrophin, yet transverse sections show a small percentage of fibers (termed "revertant fibers" positive for dystrophin expression. This phenomenon, whose biological bases have not been fully elucidated, is present also in the murine and canine models of DMD and can confound the evaluation of therapeutic approaches. We analyzed 11 different muscles in a cohort of 40 mdx mice, the most commonly model used in pre-clinical studies, belonging to four age groups; such number of animals allowed us to perform solid ANOVA statistical analysis. We assessed the average number of dystrophin-positive fibers, both absolute and normalized for muscle size, and the correlation between their formation and the ageing process. Our results indicate that various muscles develop different numbers of revertant fibers, with different time trends; besides, they suggest that the biological mechanism(s behind dystrophin re-expression might not be limited to the early development phases but could actually continue during adulthood. Importantly, such finding was seen also in cardiac muscle, a fact that does not fit into the current hypothesis of the clonal origin of "revertant" myonuclei from satellite cells. This work represents the largest, statistically significant analysis of revertant fibers in mdx mice so far, which can now be used as a reference point for improving the evaluation of therapeutic approaches for DMD. At the same time, it provides new clues about the formation of revertant fibers/cardiomyocytes in dystrophic skeletal and cardiac muscle.

  3. Nanodiamond-DGEA peptide conjugates for enhanced delivery of doxorubicin to prostate cancer

    Directory of Open Access Journals (Sweden)

    Amanee D Salaam


    Full Text Available The field of nanomedicine has emerged as an approach to enhance the specificity and efficacy of cancer treatments as stand-alone therapies and in combination with standard chemotherapeutic treatment regimens. The current standard of care for metastatic cancer, doxorubicin (DOX, is presented with challenges, namely toxicity due to a lack of specificity and targeted delivery. Nano-enabled targeted drug delivery systems can provide an avenue to overcome these issues. Nanodiamonds (ND, in particular, have been researched over the past five years for use in various drug delivery systems but minimal work has been done that incorporates targeting capability. In this study, a novel targeted drug delivery system for bone metastatic prostate cancer was developed, characterized, and evaluated in vitro. NDs were conjugated with the Asp–Gly–Glu–Ala (DGEA peptide to target α2β1 integrins over-expressed in prostate cancers during metastasis. To facilitate drug delivery, DOX was adsorbed to the surface of the ND-DGEA conjugates. Successful preparation of the ND-DGEA conjugates and the ND-DGEA+DOX system was confirmed with transmission electron microscopy, hydrodynamic size, and zeta potential measurements. Since traditional DOX treatment regimens lack specificity and increased toxicity to normal tissues, the ND-DGEA conjugates were designed to distinguish between cells that overexpress α2β1 integrin, bone metastatic prostate cancers cells (PC3, and cells that do not, human mesenchymal stem cells (hMSC. Utilizing the ND-DGEA+DOX system, the efficacy of 1 µg/mL and 2 µg/mL DOX doses increased from 2.5% to 12% cell death and 11% to 34% cell death, respectively. These studies confirmed that the delivery and efficacy of DOX were enhanced by ND-DGEA conjugates. Thus, the targeted ND-DGEA+DOX system provides a novel approach for decreasing toxicity and drug doses.

  4. Prostate Cancer Foundation (United States)

    ... P 2 rovocative Questions PCCTC Scientific Retreat Coffey-Holden Research News Faces of Prostate Cancer [4] Survivors ... Foundation News The Prostate Cancer Foundation’s 2016 Coffey-Holden Prostate Cancer Academy Meeting accelerates advances in the ...

  5. Prostate Cancer Symptoms (United States)

    ... Patient Support Guides Why no symptoms? Because prostate cancer hardly ever starts in the most convenient part of the prostate for symptoms to occur, near the urethra (the tube that carries urine through the prostate ...

  6. Seminal plasma proteins interacting with sperm surface revert capacitation indicators in frozen-thawed ram sperm. (United States)

    Ledesma, Alba; Fernández-Alegre, Estela; Cano, Adriana; Hozbor, Federico; Martínez-Pastor, Felipe; Cesari, Andreína


    This study was conducted to evaluate the effects of interacting seminal plasma proteins (iSPP) obtained by AV or EE on frozen-thawed ram sperm in order to test the hypothesis whether this fraction could be sufficient to emulate the effect of complete seminal plasma (SP). Additionally, we evaluated whether these proteins have a differential effect between spermatozoa from high and low fertility rams and between breeding and non-breeding seasons. We assessed sperm motility, quality parameters (intracellular reactive oxygen species, membrane fluidity, plasma membrane permeability and mitochondrial activity) and capacitation status. The main findings from this work were: i) iSPP had no effect on sperm motility, whereas SP (AV or EE) addition produced the highest values of total motility (74.13±2.99 and 72.27±2.99 for AV and EE, respectively) and progressive motility (64.97±2.64 and 63.73±2.64 for AV and EE, respectively); ii) iSPP had no effect on sperm quality parameters (p>0.05), but whole SP improved all parameters evaluated. Moreover, SP collected by AV yielded significantly higher viability (44.60±2.87) and sperm with stable plasma membrane (44.56±2.49) comparing with the addition of SP collected by EE (35.80±2.47 and 36.67±1.71, respectively); iii) iSPP and SP collected by EE, but not by AV, reverted molecular signals of capacitation as protein tyrosine phosphorylation caused by freezing temperatures; iv) there were no effects of fertility or season in sperm quality parameters evaluated. This study demonstrated that, although the iSPP have a clear decapacitating effect, including the ability to revert cryo-capacitation indicators, they are not sufficient to emulate the effects of complete SP regarding sperm functional parameters.

  7. Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Scott Eggener


    Full Text Available Prostate cancer continues to be a significant public health issue worldwide, particularly in countries where men have life expectancies long enough to clinically manifest the disease. In many countries, it remains one of the leading causes of cancer-related morbidity and mortality.

  8. Significance of prostatic weight in prostatism

    DEFF Research Database (Denmark)

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


    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...

  9. Empirical features of the second-generation target zone models : Mean-reverting fundamentals and endogenous devaluation risk

    NARCIS (Netherlands)

    Knot, K.H.W.; Dijkstra, T.K.; de Haan, J.


    We show that within Bertola and Svensson's second-generation target zone model, mean-reverting interventions and endogenous devaluation risk are closely interrelated. Over the period 1983-93 we analyze the degree of mean reversion in the underlying fundamental process as well as the term structure o

  10. Revertants of the amylose-free (amf) potato clone 86.040 (2n=1x=12)

    NARCIS (Netherlands)

    Jacobsen, Evert; KRIJGSHELD, HT; Hermelink, J; Ponstein, A.S.; Witholt, Bernard; Feenstra, W.J.


    The amylose-free (amf) potato clone 86.040 (2n = 1x = 12), in which the enzyme granule bound starch synthase (GBSS) is affected, has been used for the induction and isolation of revertants with loosely branched amylopectin. Screening of 5500 microtubers, which were induced on stem segments of 685 ir

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

    NARCIS (Netherlands)

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


    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;

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

    Energy Technology Data Exchange (ETDEWEB)

    White, Thornton C [SCRA Appiled R& D


    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

  13. Significance of prostatic weight in prostatism

    DEFF Research Database (Denmark)

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


    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....... Resected prostatic weight correlated with estimated weight at cystoscopy and with obstructive symptoms, but not with urodynamic variables of infravesical obstruction. Patients with small prostates improved symptomatologically to the same degree as patients with larger glands, although they did not improve...... to the same degree urodynamically. Prostatic weight, therefore, could not be used to predict the outcome of transurethral surgery....

  14. Vaccine Treatment for Prostate Cancer (United States)

    ... Back After Treatment Prostate Cancer Treating Prostate Cancer 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 ...

  15. Isoorientin reverts TNF-α-induced insulin resistance in adipocytes activating the insulin signaling pathway. (United States)

    Alonso-Castro, Angel Josabad; Zapata-Bustos, Rocio; Gómez-Espinoza, Guadalupe; Salazar-Olivo, Luis A


    Isoorientin (ISO) is a plant C-glycosylflavonoid with purported antidiabetic effects but unexplored mechanisms of action. To gain insight into its antidiabetic mechanisms, we assayed nontoxic ISO concentrations on the 2-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2-deoxy-d-glucose (2-NBDG) uptake by murine 3T3-F442A and human sc adipocytes. In insulin-sensitive adipocytes, ISO stimulated the 2-NBDG uptake by 210% (murine) and 67% (human), compared with insulin treatment. Notably, ISO also induced 2-NBDG uptake in murine (139%) and human (60%) adipocytes made resistant to insulin by treatment with TNF-α, compared with the incorporation induced in these cells by rosiglitazone. ISO induction of glucose uptake in adipocytes was abolished by inhibitors of the insulin signaling pathway. These inhibitors also blocked the proper phosphorylation of insulin signaling pathway components induced by ISO in both insulin-sensitive and insulin-resistant adipocytes. Additionally, ISO stimulated the transcription of genes encoding components of insulin signaling pathway in murine insulin-sensitive and insulin-resistant adipocytes. In summary, we show here that ISO exerts its antidiabetic effects by activating the insulin signaling pathway in adipocytes, reverts the insulin resistance caused in these cells by TNF-α by stimulating the proper phosphorylation of proteins in this signaling pathway, and induces the expression of genes encoding these proteins.

  16. Zibibbo nero characterization, a red-wine grape revertant of muscat of Alexandria. (United States)

    De Lorenzis, Gabriella; Squadrito, Margherita; Brancadoro, Lucio; Scienza, Attilio


    Muscat of Alexandria is known in Italy as Zibibbo. Zibibbo nero, red-wine grapes, is a sport mutation of Zibibbo variety. A biochemical and molecular characterization of berry colour (VvMybA1 and VvMybA2 genes, Vitis vinifera MYeloBlastosis) and aroma Muscat (VvDXS gene, 1-deoxy-D-xylulose 5-phosphate synthase) traits in both Zibibbo cultivars was performed, as well as ampelographic and genetic identification analyses. Molecular investigations were performed also for two putative Zibibbo parents (Moscato Bianco and Triboto), in order to prove the white-to-red shift of the red-skinned mutant. Ampelographic and genetic analysis demonstrated the high similarity between Zibibbo and Zibibbo nero, as well as a comparable aroma profile, characterized mainly by high content of linalool, geranic acid and geraniol (about 70 %). The Zibibbo nero anthocyanin profile was characterized by a high proportion in cyanidin-3-O-glucoside (about 69.23 %). The molecular characterization of VvMybA1 and VvMybA2 locus detected non-functional alleles for white-skinned samples, while also the functional alleles were observed for red-skinned samples. About the VvDXS locus, the aromatic varieties showed the typical pattern of Muscat variety, while Triboto (Zibibbo parent) showed the non-Muscat-like flavour pattern. The colour locus structure of Zibibbo and its putative parents suggested that Zibibbo nero is a berry colour revertant of Zibibbo.

  17. Triazole RGD antagonist reverts TGFβ1-induced endothelial-to-mesenchymal transition in endothelial precursor cells. (United States)

    Bianchini, Francesca; Peppicelli, Silvia; Fabbrizzi, Pierangelo; Biagioni, Alessio; Mazzanti, Benedetta; Menchi, Gloria; Calorini, Lido; Pupi, Alberto; Trabocchi, Andrea


    Fibrosis is the dramatic consequence of a dysregulated reparative process in which activated fibroblasts (myofibroblasts) and Transforming Growth Factor β1 (TGFβ1) play a central role. When exposed to TGFβ1, fibroblast and epithelial cells differentiate in myofibroblasts; in addition, endothelial cells may undergo endothelial-to-mesenchymal transition (EndoMT) and actively participate to the progression of fibrosis. Recently, the role of αv integrins, which recognize the Arg-Gly-Asp (RGD) tripeptide, in the release and signal transduction activation of TGFβ1 became evident. In this study, we present a class of triazole-derived RGD antagonists that interact with αvβ3 integrin. Above different compounds, the RGD-2 specifically interferes with integrin-dependent TGFβ1 EndoMT in Endothelial Colony-Forming Cells (ECPCs) derived from circulating Endothelial Precursor Cells (ECPCs). The RGD-2 decreases the amount of membrane-associated TGFβ1, and reduces both ALK5/TGFβ1 type I receptor expression and Smad2 phosphorylation in ECPCs. We found that RGD-2 antagonist reverts EndoMT, reducing α-smooth muscle actin (α-SMA) and vimentin expression in differentiated ECPCs. Our results outline the critical role of integrin in fibrosis progression and account for the opportunity of using integrins as target for anti-fibrotic therapeutic treatment.

  18. Sunitinib Improves Some Clinical Aspects and Reverts DMBA-Induced Hyperplasic Lesions in Hamster Buccal Pouch (United States)

    de Souza, Fernanda Lopes; Oliveira, Mariana; Nunes, Marianne Brochado; Serafim, Lucas Horstmann; Azambuja, Alan Arrieira; Braga, Luisa Maria G. de M.; Saur, Lisiani; de Souza, Maria Antonieta Lopes; Xavier, Léder Leal


    Oral squamous cell carcinoma (OSCC) is a public health problem. The hamster buccal pouch model is ideal for analyzing the development of OSCC. This research analysed the effects of sunitinib (tyrosine kinase inhibitor) in precancerous lesions induced by 7,12-dimethylbenz(a)anthracene (DMBA) in this model. Thirty-four male hamsters, divided into six groups: control—C (n = 7), acetone—A (n = 12), carbamide peroxide—CP (n = 5 ), acetone and CP—A+CP (n = 8), 1% DMBA in acetone and CP—DA+CP (n = 6), and 1% DMBA in acetone and CP and 4-week treatment with sunitinib—DA+CP+S (n = 7). The aspects evaluated were anatomopathological features (peribuccal area, paws, nose, and fur), histological sections of the hamster buccal pouches (qualitatively analyzed), epithelium thickness, and the rete ridge density (estimated). Sunitinib was unable to attenuate the decrease in weight gain induced by DMBA; no increase in volume was detected in the pouch and/or ulceration, observed in 43% of the animals in the DA+CP group. DA+CP groups presented a significant increase in rete ridge density compared to the control groups (P < 0.01) which was reverted by sunitinib in the DA+CP+S group. Sunitinib seems to have important benefits in early stage carcinogenesis and may be useful in chemoprevention. PMID:24693453

  19. Keeping it simple: flowering plants tend to retain, and revert to, simple leaves. (United States)

    Geeta, R; Dávalos, Liliana M; Levy, André; Bohs, Lynn; Lavin, Mathew; Mummenhoff, Klaus; Sinha, Neelima; Wojciechowski, Martin F


    • A wide range of factors (developmental, physiological, ecological) with unpredictable interactions control variation in leaf form. Here, we examined the distribution of leaf morphologies (simple and complex forms) across angiosperms in a phylogenetic context to detect patterns in the directions of changes in leaf shape. • Seven datasets (diverse angiosperms and six nested clades, Sapindales, Apiales, Papaveraceae, Fabaceae, Lepidium, Solanum) were analysed using maximum likelihood and parsimony methods to estimate asymmetries in rates of change among character states. • Simple leaves are most frequent among angiosperm lineages today, were inferred to be ancestral in angiosperms and tended to be retained in evolution (stasis). Complex leaves slowly originated ('gains') and quickly reverted to simple leaves ('losses') multiple times, with a significantly greater rate of losses than gains. Lobed leaves may be a labile intermediate step between different forms. The nested clades showed mixed trends; Solanum, like the angiosperms in general, had higher rates of losses than gains, but the other clades had higher rates of gains than losses. • The angiosperm-wide pattern could be taken as a null model to test leaf evolution patterns in particular clades, in which patterns of variation suggest clade-specific processes that have yet to be investigated fully.

  20. Risks of Prostate Cancer Screening (United States)

    ... prostate may be similar to symptoms of prostate cancer . Enlarge Normal prostate and benign prostatic hyperplasia (BPH). A normal prostate does not block the flow of urine from the bladder. An enlarged prostate presses on the bladder and urethra and blocks the flow of urine. See the ...

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

    Directory of Open Access Journals (Sweden)

    Monika Schmelz


    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.

  2. Baicalein reverts L-valine-induced persistent sodium current up-modulation in primary cortical neurons. (United States)

    Caioli, Silvia; Candelotti, Elena; Pedersen, Jens Z; Saba, Luana; Antonini, Alessia; Incerpi, Sandra; Zona, Cristina


    L-valine is a branched-chain amino acid (BCAA) largely used as dietary integrator by athletes and involved in some inherited rare diseases such as maple syrup urine disease. This pathology is caused by an altered BCAA metabolism with the accumulation of toxic keto acids in tissues and body fluids with consequent severe neurological symptoms. In animal models of BCAA accumulation, increased oxidative stress levels and lipid peroxidation have been reported. The aim of this study was to analyze both whether high BCAA concentrations in neurons induce reactive oxygen species (ROS) production and whether, by performing electrophysiological recordings, the neuronal functional properties are modified. Our results demonstrate that in primary cortical cultures, a high dose of valine increases ROS production and provokes neuronal hyperexcitability because the action potential frequencies and the persistent sodium current amplitudes increase significantly compared to non-treated neurons. Since Baicalein, a flavone obtained from the Scutellaria root, has been shown to act as a strong antioxidant with neuroprotective effects, we evaluated its possible antioxidant activity in primary cortical neurons chronically exposed to L-valine. The preincubation of cortical neurons with Baicalein prevents the ROS production and is able to revert both the neuronal hyperexcitability and the increase of the persistent sodium current, indicating a direct correlation between the ROS production and the altered physiological parameters. In conclusion, our data show that the electrophysiological alterations of cortical neurons elicited by high valine concentration are due to the increase in ROS production, suggesting much caution in the intake of BCAA dietary integrators.

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

    Directory of Open Access Journals (Sweden)

    Heike eBenecke


    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.

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

    Directory of Open Access Journals (Sweden)

    Sam eAgus


    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.

  5. Granulomatous prostatitis - an infrequent diagnosis

    Directory of Open Access Journals (Sweden)

    RPS Punia


    Full Text Available Granulomatous prostatitis is a rare disorder of pros-tate. We encountered 10 cases of′grmudomatous prosta-titis consisting of 5 cases of non-specific granulomatous prostatitis, 2 cases of xanthogranulomatous prostatitis, I case of tuberculous prostatitis, I case of malakoplakia prostate and I case of granulomatous prostatitis associ-ated with adenocarcinoma prostate. The diagnosis was made by histopathologic examination of trucut biopsy, TURP chips or retropubic prostatectomy specimen. In all the cases, granulomatous prostatitis was an incidental find-ing.

  6. Construction and Genetic Analysis of Murine Hepatitis Virus Strain A59 Nsp16 Temperature Sensitive Mutant and the Revertant Virus

    Institute of Scientific and Technical Information of China (English)

    Guo-hui Chang; Bao-jun Luo; Pin Lu; Lei Lin; Xiao-yan Wu; Jing Li; Yi Hu; Qing-yu Zhu


    Coronaviruses (CoVs) are generally associated with respiratory and enteric infections and have long been recognized as important pathogens of livestock and companion animals. Mouse hepatitis virus (MHV) is a widely studied model system for Coronavirus replication and pathogenesis. In this study, we created a MHV-A59 temperature sensitive (ts) mutant Wu"-ts18(cd) using the recombinant vaccinia reverse genetics system. Virus replication assay in 17C1-1 cells showed the plaque phenotype and replication characterization of constructed Wu"-ts18(cd) were indistinguishable from the reported ts mutant Wu"-ts 18. Then we cultured the ts mutant Wu"-ts 18(cd) at non-permissive temperature 39.5℃, which "forced" the ts recombinant virus to use second-site mutation to revert from a ts to a non-ts phenotype. Sequence analysis showed most of the revertants had the same single amino acid mutation at Nsp16 position 43. The single amino acid mutation at Nsp16 position 76 or position 130 could also revert the ts mutant Wu"-ts 18 (cd) to non-ts phenotype, an additional independent mutation in Nsp13 position 115 played an important role on plaque size. The results provided us with genetic information on the functional determinants of Nsp16. This allowed us to build up a more reasonable model of CoVs replication-transcription complex.


    Directory of Open Access Journals (Sweden)

    Blinova M. P.


    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

  8. Late-Onset Combined Immunodeficiency with a Novel IL2RG Mutation and Probable Revertant Somatic Mosaicism. (United States)

    Okuno, Yusuke; Hoshino, Akihiro; Muramatsu, Hideki; Kawashima, Nozomu; Wang, Xinan; Yoshida, Kenichi; Wada, Taizo; Gunji, Masaharu; Toma, Tomoko; Kato, Tamaki; Shiraishi, Yuichi; Iwata, Atsuko; Hori, Toshinori; Kitoh, Toshiyuki; Chiba, Kenichi; Tanaka, Hiroko; Sanada, Masashi; Takahashi, Yoshiyuki; Nonoyama, Shigeaki; Ito, Masafumi; Miyano, Satoru; Ogawa, Seishi; Kojima, Seiji; Kanegane, Hirokazu


    Primary immunodeficiency disease (PID) is caused by mutations of more than two hundred immunity-related genes. In addition to the heterogeneity of the diseases, the atypical presentation of each disease caused by hypomorphic mutations or somatic mosaicism makes genetic diagnosis challenging. Next-generation sequencing tests all genes simultaneously and has proven its innovative efficacy in genomics. We describe a male PID patient without any family history of immunodeficiency. This patient suffered from recurrent infections from 1 year of age. Laboratory analysis showed hypogammaglobulinemia. T, B, and NK cells were present, but the T cell proliferative response decreased. Whole-exome sequencing analysis identified an IL2RG p.P58T missense mutation. CD8(+) and CD56(+) cells showed revertant somatic mosaicism to the wild-type allele. A late-onset and atypical presentation of the X-linked severe combined immunodeficiency (X-SCID) phenotype might be associated with revertant somatic mosaicism in T and NK cells. This patient is the seventh reported case of X-SCID with revertant somatic mosaicism. His classical clinical management did not result in a molecular diagnosis because of the atypical presentation. The coverage that is provided by whole-exome sequencing of most PID genes effectively excluded differential diagnoses other than X-SCID. As next-generation sequencing becomes available in clinical practice, it will enhance our knowledge of PID and rescue currently undiagnosed patients.

  9. [Benign prostatic hypertrophy and prostate cancer]. (United States)

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


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

  10. Prostate cancer in Denmark

    DEFF Research Database (Denmark)

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


    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....

  11. Prostate Cancer FAQs (United States)

    ... of Prostate Cancer Annual Report & Financials Our Leadership Leadership Team Board Members A Legacy of Leadership Featured Take ... Partners Faces of Prostate Cancer Annual Report & Financials Leadership Team Board Members Featured A Legacy of Leadership Take ...

  12. Cryotherapy for prostate cancer (United States)

    ... this page: // Cryotherapy for prostate cancer To use the sharing features ... first treatment for prostate cancer. What Happens During Cryotherapy Before the procedure, you will be given medicine ...

  13. About the Prostate (United States)

    ... develops from the transition zone that surrounds the urethra, or urinary tube. This is why BPH may cause more difficulty with urination than prostate cancer typically does. Treatment-Related Changes Because the prostate ...

  14. Learning about Prostate Cancer (United States)

    ... diagnosed and treated? Symptoms : The symptoms of prostate cancer may include problems with urination and sexual function. As the prostate grows larger it can squeeze the urethra and cause frequent, small urination, difficulty beginning urination ...

  15. Revertant mosaicism for family mutations is not observed in BRCA1/2 phenocopies (United States)

    Azzollini, Jacopo; Pesenti, Chiara; Ferrari, Luca; Fontana, Laura; Calvello, Mariarosaria; Peissel, Bernard; Portera, Giorgio; Tabano, Silvia; Carcangiu, Maria Luisa; Riva, Paola; Manoukian, Siranoush


    In BRCA1/2 families, early-onset breast cancer (BrCa) cases may be also observed among non-carrier relatives. These women are considered phenocopies and raise difficult counselling issues concerning the selection of the index case and the residual risks estimate in negative family members. Few studies investigated the presence of potential genetic susceptibility factors in phenocopies, mainly focussing on BrCa-associated single-nucleotide polymorphisms. We hypothesized that, as for other Mendelian diseases, a revertant somatic mosaicism, resulting from spontaneous correction of a pathogenic mutation, might occur also in BRCA pedigrees. A putative low-level mosaicism in phenocopies, which has never been investigated, might be the causal factor undetected by standard diagnostic testing. We selected 16 non-carriers BrCa-affected from 15 BRCA1/2 families, and investigated the presence of mosaicism through MALDI-TOF mass spectrometry. The analyses were performed on available tumour samples (7 cases), blood leukocytes, buccal mucosa and urine samples (2 cases) or on blood only (7 cases). In one family (n.8), real-time PCR was also performed to analyse the phenocopy and her healthy parents. On the 16 phenocopies we did not detect the family mutations neither in the tumour, expected to display the highest mutation frequency, nor in the other analysed tissues. In family 8, all the genotyping assays did not detect mosaicism in the phenocopy or her healthy parents, supporting the hypothesis of a de novo occurrence of the BRCA2 mutation identified in the proband. These results suggest that somatic mosaicism is not likely to be a common phenomenon in BRCA1/2 families. As our families fulfilled high-risk selection criteria, other genetic factors might be responsible for most of these cases and have a significant impact on risk assessment in BRCA1/2 families. Finally, we found a de novo BRCA2 mutation, suggesting that, although rare, this event should be taken into account in the

  16. [Prostatic abscesses. A review]. (United States)

    Rabii, R; Rais, H; Joual, A; el Mrini, M; Benjelloun, S


    We review the literature to the diagnosis and therapeutic aspect of prostatic abscess. The prostatic abscess having become an uncommon disease. The diagnosis of prostatic abscess has been nearly made by transrectal ultrasound and computed tomography scan. The best diagnostic method is considered to be the transrectal ultrasound. The choice therapy was intravenous antibiotic, and drainage by ultrasound guided transperineal percutaneous puncture.

  17. What is Prostate Cancer? (United States)

    ... make most of the fluid for semen. The urethra, which is the tube that carries urine and semen out of the body through the penis, goes through the center of the prostate. Types of prostate cancer Almost all prostate cancers are adenocarcinomas . These cancers ...

  18. Prostate resection - minimally invasive (United States)

    ... invasive URL of this page: // Prostate resection - minimally invasive To use ... into your bladder instead of out through the urethra ( retrograde ... on New Developments in Prostate Cancer and Prostate Diseases. Evaluation and treatment of lower ...

  19. Linking Estrogens, Prostatitis and Prostate Cancer (United States)


    provide the first direct evidence linking phy siologic estr ogen up- regulation an d pr ostate ma lignancy via inflammation. Ellem, Stuart J...inflammation and malignancy in the prostate. The identification of estr ogen as a cause of prostatitis, as well as a fac tor in the development of

  20. Danish Prostate Cancer Registry

    DEFF Research Database (Denmark)

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


    of the prostate (TUR-Ps), and the remaining 22,028 (13.6%) specimens were derived from radical prostatectomies, bladder interventions, etc. A total of 48,078 (42.2%) males had histopathologically verified prostate cancer, and of these, 78.8% and 16.8% were diagnosed on prostate biopsies and TUR-Ps, respectively....... FUTURE PERSPECTIVES: A validated algorithm was successfully developed to convert complex prostate SNOMED codes into clinical useful data. A unique database, including males with both normal and cancerous histopathological data, was created to form the most comprehensive national prostate database to date...

  1. Ultrasound- and MRI-Guided Prostate Biopsy (United States)

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

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

    Directory of Open Access Journals (Sweden)

    Isaac Gómez Laguna


    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.

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


    Isaac Gómez Laguna


    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...

  4. La tabla de Flandes, de Arturo Pérez Reverte: cifra de las pasiones humanas


    Borowski de Llanos, Haydée; Escalada, María Aurelia; García Saraví, Mercedes


    Siguiendo la línea de aproximación a la obra de Arturo Pérez Reverte, nos proponemos investigar acerca de procedimientos y modalidades textuales en función de la hibridez genérica que lo caracteriza. Nos centraremos en La tabla de Flandes de 1990, ya que en trabajos anteriores hemos indagado publicaciones más recientes. La estrategia revertiana ha ido modificándose paulatinamente desde sus comienzos como narrador, y considerar esta novela nos permitirá visualizar uno de los puntos de partida ...

  5. Hormone Therapy for Prostate Cancer (United States)

    ... Galvão DA, Taaffe DR, Spry N, Newton RU. Exercise can prevent and even reverse adverse effects of androgen suppression treatment in men with prostate cancer. Prostate Cancer and Prostatic Diseases 2007; 10(4): ...

  6. TRP Channels in Human Prostate

    Directory of Open Access Journals (Sweden)

    Carl Van Haute


    Full Text Available This review gives an overview of morphological and functional characteristics in the human prostate. It will focus on the current knowledge about transient receptor potential (TRP channels expressed in the human prostate, and their putative role in normal physiology and prostate carcinogenesis. Controversial data regarding the expression pattern and the potential impact of TRP channels in prostate function, and their involvement in prostate cancer and other prostate diseases, will be discussed.

  7. Chemopreventive effect of quercetin in MNU and testosterone induced prostate cancer of Sprague-Dawley rats. (United States)

    Sharmila, Govindaraj; Athirai, Thavadurainathan; Kiruthiga, Balakrishnan; Senthilkumar, Kalimuthu; Elumalai, Perumal; Arunkumar, Ramachandran; Arunakaran, Jagadeesan


    Prostate cancer becomes an ideal target for chemoprevention because of its high incidence and extended natural history. The consumption of quercetin (plant flavonoid) in diet is associated with decreased risk of disease and many cancers but then this was not elucidated in prostate malignancy. Hence, a study in which the male Sprague-Dawley rats were induced prostate cancer by hormone (testosterone) and carcinogen (MNU) and simultaneously supplemented with quercetin (200 mg/Kg body weight) thrice a week, was conducted. After the treatment period, rats were killed; ventral and dorsolateral lobes of the prostate were dissected. Histology and oxidative stress markers LPO, H2O2, and antioxidant GSH level were measured in both lobes. The lipid peroxidation, H2O2, in (MNU+T) treated rats were increased and GSH level was decreased, whereas simultaneous quercetin-treated rats reverted back to normal level in both ventral and dorsolateral regions. The different patterns of PIN were observed with associated hyperplasia and dysplasia; changes in these regions and the occurrence of this lesion were reduced in simultaneous quercetin-treated rats. The study concluded that dietary quercetin prevented MNU + T-induced prostate carcinogenesis on both ventral and dorsolateral lobes of Sprague-Dawley rats.

  8. The Lifestyle Carbon Dividend: Assessment of the Carbon Sequestration Potential of Grasslands and Pasturelands Reverted to Native Forests (United States)

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


    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.

  9. Nonspecific granulomatous prostatitis with prostatic adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Murugan Paari


    Full Text Available Granulomatous prostatitis is an infrequently seen entity in routine practice. One of its most common subtypes is nonspecific granulomatous prostatitis (NSGP, the etiology of which is still under debate. Such cases may be mistaken for adenocarcinoma clinically and radiologically. Histological resemblance to adenocarcinoma may arise when there is a xanthogranulomatous pattern or a prominence of epithelioid histiocytes. However, NSGP may rarely coexist with adenocarcinoma and it is critical to sample these cases thoroughly to exclude the presence of malignancy.

  10. Stromal microcalcification in prostate. (United States)

    Muezzinoglu, B; Gurbuz, Y


    Prostatic calcification is most commonly encountered as calculus or intraluminal calcifications within atypical small glandular proliferations. This study was undertaken to detect stromal microcalcifications in prostate tissue. All slides from 194 needle biopsies were retrospectively reviewed. Six cases (3.1%) had stromal microcalcifications constantly associated with mononuclear inflammatory infiltrate around the each focus. Association with prostatic glands was not seen in any of the microcalcification foci. Three cases had simultaneous adenocarcinoma and one had high-grade prostatic intraepithelial neoplasia, all of which were apart from the microcalcification foci. In conclusion, stromal microcalcification is a dystrophic, inflammation-mediated, benign process.

  11. [Imaging of cancer prostate]. (United States)

    Ghouadni, Mehdi; Sandoz, Catherine; Eiss, David; Cornud, François; Thiounn, Nicolas; Hélénon, Olivier


    Imaging of prostate cancer relies mainly on ultrasonography (US) and magnetic resonance imaging (MRI). It plays a diagnostic role in detecting and staging prostate carcinomas. Prostate biopsies are performed under endorectal US guidance at best with additional colour Doppler information. US also may provide useful information regarding the significance of an abnormal digital rectal examination sometimes related to some benign prostate alterations that can mimic a neoplastic nodule. In all cases imaging studies need to be interpreted in light of clinical and biological data including the results of biopsy especially in staging carcinoma with MR. Finally, CT and scintigraphy are helpful in screening for distant metastases.

  12. Living with Prostate Cancer (United States)

    ... cancer treatment and can improve many aspects of health, including muscle strength, balance, fatigue, cardiovascular fitness, and depression. Physical activity after a prostate cancer diagnosis is linked to ...

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

    Directory of Open Access Journals (Sweden)

    P. S. Zubeev


    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.

  14. El club Dumas d’Arturo Pérez-Reverte ou une métaphore de la lecture


    Marie-Thérèse Garcia


    Corso, personnage-lecteur de El club Dumas d’Arturo Pérez-Reverte assiste impuissant à la contamination de son univers référentiel « réel dans le roman » par des êtres de fiction issus des Trois mousquetaires d’Alexandre Dumas. Gagné peu à peu par le syndrome de don Quichotte, le détective de livres interprète sa réalité fictionnelle à travers le prisme de son imaginaire. L’infortuné Corso, dupé par un narrateur-personnage d’une mauvaise foi aussi efficace que redoutable et manipulé par un au...

  15. L’Enquêteur quitte la scène. Arturo Pérez-Reverte, La Tabla de Flandes


    Bonnaffoux, Denise


    Un assassinat au XVe siècle, non élucidé, découvert au hasard de la restauration d’un tableau d’un maître flamand, conduit à un enchaînement d’assassinats dans le Madrid de la fin du XXe siècle. Folie ? Délire des personnages ? Pourtant Arturo Pérez-Reverte ne verse pas là dans la littérature fantastique. Julia, l’héroïne en danger, César, son vieil ami fidèle, et Muñoz, joueur d’échecs d’élite qui trouvera la clé de l’énigme en continuant la partie restée en suspens sur l’échiquier de la toi...

  16. Fluoxetine reverts chronic restraint stress-induced depression-like behaviour and increases neuropeptide Y and galanin expression in mice

    DEFF Research Database (Denmark)

    Christiansen, Søren Hofman Oliveira; Olesen, Mikkel Vestergaard; Wörtwein, Gitta


    -like behaviour, NPY and galanin gene expression was studied in brains of mice subjected to chronic restraint stress (CRS) and concomitant treatment with the antidepressant fluoxetine (FLX). CRS caused a significant increase in depression-like behaviour that was associated with increased NPY mRNA levels......Stressful life events and chronic stress are implicated in the development of depressive disorder in humans. Neuropeptide Y (NPY) and galanin have been shown to modulate the stress response, and exert antidepressant-like effects in rodents. To further investigate these neuropeptides in depression...... in the medial amygdala. Concomitant FLX treatment reverted depression-like effects of CRS and led to significant increases in levels of NPY and galanin mRNA in the dentate gyrus, amygdala, and piriform cortex. These findings suggest that effects on NPY and galanin gene expression could play a role...

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

    DEFF Research Database (Denmark)

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


    the 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......), in the presence or absence of inhibitors, showed that these compounds function well. All the resistance modifying agents potentiated IDA activity inducing a significant reduction (P... 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...

  18. Tuberculous prostatitis: mimicking a cancer. (United States)

    Aziz, El Majdoub; Abdelhak, Khallouk; Hassan, Farih Moulay


    Genitourinary tuberculosis is a common type of extra-pulmonary tuberculosis . The kidneys, ureter, bladder or genital organs are usually involved. Tuberculosis of the prostate has mainly been described in immune-compromised patients. However, it can exceptionally be found as an isolated lesion in immune-competent patients. Tuberculosis of the prostate may be difficult to differentiate from carcinoma of the prostate and the chronic prostatitis when the prostate is hard and nodular on digital rectal examination and the urine is negative for tuberculosis bacilli. In many cases, a diagnosis of tuberculous prostatitis is made by the pathologist, or the disease is found incidentally after transurethral resection. Therefore, suspicion of tuberculous prostatitis requires a confirmatory biopsy of the prostate. We report the case of 60-year-old man who presented a low urinary tract syndrome. After clinical and biological examination, and imaging, prostate cancer was highly suspected. Transrectal needle biopsy of the prostate was performed and histological examination showed tuberculosis lesions.

  19. Optimizing prostate biopsy for repeat transrectal prostate biopsies patients

    Institute of Scientific and Technical Information of China (English)

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


    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.

  20. The Prostate Exam (United States)

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


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

  1. Cryosurgery for prostate cancer. (United States)

    Fahmy, W E; Bissada, N K


    Choice of management for patients with prostate cancer is influenced by patient and disease characteristics and life expectancy. Management options include expectance (watchful waiting), radical prostatectomy, external beam radiotherapy, brachytherapy, and cryosurgical ablation of the prostate (CSAP). The role of cryotherapy in the management of prostate cancer is still evolving. Continued research has allowed the introduction of efficient and safe cryosurgical equipment exemplified by the current third-generation cryosurgical machines. CSAP can be performed in an ambulatory surgery setting or as inpatient surgery with overnight stay. The procedure is performed under continuous ultrasonic monitoring. Mature data from the use of second-generation cryosurgical equipment indicate that CSAP is an effective therapeutic modality for managing patients with prostate cancer. Current data with the third-generation cryosurgical equipment are not mature. However, the favorable side effect profile and the good early responses seem to indicate that this modality will have a prominent role in the management of patients with prostate cancer.

  2. Epidemiology of Prostate Cancer. (United States)

    Bashir, Muhammad Naeem


    Prostate cancer is the most common malignancy among males worldwide, and is the second leading cause of cancer death among men in United States. According to GLOBOCAN (2012), an estimated 1.1 million new cases and 307,000 deaths were reported in 2012. The reasons for the increase of this disease are not known, but increasing life expectancy and modified diagnostic techniques have been suggested as causes. The established risk factors for this disease are advancing age, race, positive family history of prostate cancer and western diet (use of fat items). Several other risk factors, such as obesity, physical activity, sexual activity, smoking and occupation have been also associated with prostate cancer risk, but their roles in prostate cancer etiology remain uncertain. This mini-review aims to provide risk factors, disease knowledge, prevalence and awareness about prostate cancer.

  3. Prostate Cancer and Sexual Function


    Hyun, Jae Saog


    Prostate cancer is now ranked fifth in incidence among cancers in Korean adult males. This is attributable to the more Westernized dietary style which increases the morbidity of prostate cancer and the development of cancer diagnostic technologies, such as prostate-specific antigen and advanced medical systems, increasing the rate of prostate cancer diagnosis. Prostate cancer effects include not only erectile dysfunction caused by the disease itself, but also by psychiatric disorders caused b...

  4. Stromal Androgen Receptor Roles in the Development of Normal Prostate, Benign Prostate Hyperplasia, and Prostate Cancer


    Wen, Simeng; Chang, Hong-Chiang; Tian, Jing; Shang, Zhiqun; Niu, Yuanjie; Chang, Chawnshang


    The prostate is an androgen-sensitive organ that needs proper androgen/androgen receptor (AR) signals for normal development. The progression of prostate diseases, including benign prostate hyperplasia (BPH) and prostate cancer (PCa), also needs proper androgen/AR signals. Tissue recombination studies report that stromal, but not epithelial, AR plays more critical roles via the mesenchymal-epithelial interactions to influence the early process of prostate development. However, in BPH and PCa,...

  5. Prostate cancer; Cancer de la prostate

    Energy Technology Data Exchange (ETDEWEB)

    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)


    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)

  6. In vivo biomarker expression patterns are preserved in 3D cultures of Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Windus, Louisa C.E.; Kiss, Debra L.; Glover, Tristan [Eskitis Institute for Cell and Molecular Therapies, Discovery Biology, Griffith University, Nathan 4111, Brisbane, Queensland (Australia); Avery, Vicky M., E-mail: [Eskitis Institute for Cell and Molecular Therapies, Discovery Biology, Griffith University, Nathan 4111, Brisbane, Queensland (Australia)


    Here we report that Prostate Cancer (PCa) cell-lines DU145, PC3, LNCaP and RWPE-1 grown in 3D matrices in contrast to conventional 2D monolayers, display distinct differences in cell morphology, proliferation and expression of important biomarker proteins associated with cancer progression. Consistent with in vivo growth rates, in 3D cultures, all PCa cell-lines were found to proliferate at significantly lower rates in comparison to their 2D counterparts. Moreover, when grown in a 3D matrix, metastatic PC3 cell-lines were found to mimic more precisely protein expression patterns of metastatic tumour formation as found in vivo. In comparison to the prostate epithelial cell-line RWPE-1, metastatic PC3 cell-lines exhibited a down-regulation of E-cadherin and {alpha}6 integrin expression and an up-regulation of N-cadherin, Vimentin and {beta}1 integrin expression and re-expressed non-transcriptionally active AR. In comparison to the non-invasive LNCaP cell-lines, PC3 cells were found to have an up-regulation of chemokine receptor CXCR4, consistent with a metastatic phenotype. In 2D cultures, there was little distinction in protein expression between metastatic, non-invasive and epithelial cells. These results suggest that 3D cultures are more representative of in vivo morphology and may serve as a more biologically relevant model in the drug discovery pipeline. -- Highlights: Black-Right-Pointing-Pointer We developed and optimised 3D culturing techniques for Prostate Cancer cell-lines. Black-Right-Pointing-Pointer We investigated biomarker expression in 2D versus 3D culture techniques. Black-Right-Pointing-Pointer Metastatic PC3 cells re-expressed non-transcriptionally active androgen receptor. Black-Right-Pointing-Pointer Metastatic PCa cell lines retain in vivo-like antigenic profiles in 3D cultures.

  7. The link between benign prostatic hyperplasia and prostate cancer

    DEFF Research Database (Denmark)

    Ørsted, David Dynnes; Bojesen, Stig E


    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....... 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...

  8. Characterization of Laminin Binding Integrin Internalization in Prostate Cancer Cells. (United States)

    Das, Lipsa; Anderson, Todd A; Gard, Jaime M C; Sroka, Isis C; Strautman, Stephanie R; Nagle, Raymond B; Morrissey, Colm; Knudsen, Beatrice S; Cress, Anne E


    Laminin binding integrins α6 (CD49f) and α3 (CD49c) are persistently but differentially expressed in prostate cancer (PCa). Integrin internalization is an important determinant of their cell surface expression and function. Using flow cytometry, and first order kinetic modeling, we quantitated the intrinsic internalization rates of integrin subunits in a single cycle of internalization. In PCa cell line DU145, α6 integrin internalized with a rate constant (kactual ) of 3.25 min(-1) , threefold faster than α3 integrin (1.0 min(-1) ), 1.5-fold faster than the vitronectin binding αv integrin (CD51) (2.2 min(-1) ), and significantly slower than the unrelated transferrin receptor (CD71) (15 min(-1) ). Silencing of α3 integrin protein expression in DU145, PC3, and PC3B1 cells resulted in up to a 1.71-fold increase in kactual for α6 integrin. The internalized α6 integrin was targeted to early endosomes but not to lamp1 vesicles. Depletion of α3 integrin expression resulted in redistribution of α6β4 integrin to an observed cell-cell staining pattern that is consistent with a suprabasal distribution observed in epidermis and early PIN lesions in PCa. Depletion of α3 integrin increased cell migration by 1.8-fold, which was dependent on α6β1 integrin. Silencing of α6 integrin expression however, had no significant effect on the kactual of α3 integrin or its distribution in early endosomes. These results indicate that α3 and α6 integrins have significantly different internalization kinetics and that coordination exists between them for internalization. J. Cell. Biochem. 118: 1038-1049, 2017. © 2016 Wiley Periodicals, Inc.

  9. Cholesterol and prostate cancer. (United States)

    Pelton, Kristine; Freeman, Michael R; Solomon, Keith R


    Prostate cancer risk can be modified by environmental factors, however the molecular mechanisms affecting susceptibility to this disease are not well understood. As a result of a series of recently published studies, the steroidal lipid, cholesterol, has emerged as a clinically relevant therapeutic target in prostate cancer. This review summarizes the findings from human studies as well as animal and cell biology models, which suggest that high circulating cholesterol increases risk of aggressive prostate cancer, while cholesterol lowering strategies may confer protective benefit. Relevant molecular processes that have been experimentally tested and might explain these associations are described. We suggest that these promising results now could be applied prospectively to attempt to lower risk of prostate cancer in select populations.

  10. Epigenetics in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Costantine Albany


    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.

  11. Prostate Cancer Foundation (United States)

    ... Financials Our Leadership Leadership Team A Legacy of Leadership Featured ... Medicine Revolution Welcome to the world of precision medicine—where doctors can target each prostate cancer with new, more effective drugs. And this is just the beginning. Learn ...

  12. Transcriptionally regulated, prostate-targeted gene therapy for prostate cancer. (United States)

    Lu, Yi


    Prostate cancer is the most frequently diagnosed cancer and the second leading cause of cancer deaths in American males today. Novel and effective treatment such as gene therapy is greatly desired. The early viral based gene therapy uses tissue-nonspecific promoters, which causes unintended toxicity to other normal tissues. In this chapter, we will review the transcriptionally regulated gene therapy strategy for prostate cancer treatment. We will describe the development of transcriptionally regulated prostate cancer gene therapy in the following areas: (1) Comparison of different routes for best viral delivery to the prostate; (2) Study of transcriptionally regulated, prostate-targeted viral vectors: specificity and activity of the transgene under several different prostate-specific promoters were compared in vitro and in vivo; (3) Selection of therapeutic transgenes and strategies for prostate cancer gene therapy (4) Oncolytic virotherapy for prostate cancer. In addition, the current challenges and future directions in this field are also discussed.

  13. Presence of PSA auto-antibodies in men with prostate abnormalities (prostate cancer/benign prostatic hyperplasia/prostatitis). (United States)

    Lokant, M T; Naz, R K


    Prostate-specific antigen (PSA), produced by the prostate, liquefies post-ejaculate semen. PSA is detected in semen and blood. Increased circulating PSA levels indicate prostate abnormality [prostate cancer (PC), benign prostatic hyperplasia (BPH), prostatitis (PTIS)], with variance among individuals. As the prostate has been proposed as an immune organ, we hypothesise that variation in PSA levels among men may be due to presence of auto-antibodies against PSA. Sera from healthy men (n = 28) and men having prostatitis (n = 25), BPH (n = 30) or PC (n = 29) were tested for PSA antibody presence using enzyme-linked immunosorbent assay (ELISA) values converted to standard deviation (SD) units, and Western blotting. Taking ≥2 SD units as cut-off for positive immunoreactivity, 0% of normal men, 0% with prostatitis, 33% with BPH and 3.45% with PC demonstrated PSA antibodies. One-way analysis of variance (anova) performed on the mean absorbance values and SD units of each group showed BPH as significantly different (P prostatitis. All others were nonsignificant (P prostate abnormalities, especially differentiating BPH from prostate cancer and prostatitis.

  14. Benign Prostatic Hyperplasia


    Gil Ortega, Joan


    Benign prostatic hyperplasia (BPH) is a prevalent disease but its molecular mechanism remains unknown. Using human tissue samples from 16 patients diagnosed with BPH, we performed an ultrastructural study to clarify the mechanism and the role of glandular cells in this pathology. We have made a description of all the changes that suffers the prostatic epithelium. We have shown that the glandular architecture presents many non-physiological forms such as papillae and papillary fronds. Basal c...

  15. Prostatitis - eine endlose Geschichte?

    Directory of Open Access Journals (Sweden)

    Riedl CR


    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".



    SILVIO ALTARAC; Galić, Josip; Vidas, Željko; Savić, Ivan; ŠTAJCAR, DAMIR; Rajković, Zoran; Arslani, Nuhi; Vučemilo, Luka; BUBNJAR, JOSIP; Papeš, Dino


    Za rak prostate može se reći da je jedan od najvažnijih medicinskih problema u muškoj populaciji. U razvoju i progresiji karcinoma prostate bitne su epigenetska regulacija ekspresije gena pomoću promotora metilacije i acetilacije histona, proupalni enzim ciklooksigenaza-2, kao i somatske mutacije različitih gena s različitim biološkim funkcijama.

  17. El club Dumas d’Arturo Pérez-Reverte ou une métaphore de la lecture

    Directory of Open Access Journals (Sweden)

    Marie-Thérèse Garcia


    Full Text Available Corso, personnage-lecteur de El club Dumas d’Arturo Pérez-Reverte assiste impuissant à la contamination de son univers référentiel « réel dans le roman » par des êtres de fiction issus des Trois mousquetaires d’Alexandre Dumas. Gagné peu à peu par le syndrome de don Quichotte, le détective de livres interprète sa réalité fictionnelle à travers le prisme de son imaginaire. L’infortuné Corso, dupé par un narrateur-personnage d’une mauvaise foi aussi efficace que redoutable et manipulé par un auteur expert en stratégie narrative, vit une aventure « métaleptique ». Par un jeu spéculaire, le comportement irrationnel du protagoniste renvoie le lecteur réel à sa propre responsabilité dans l’acte de lecture. La fable, traitée de façon ludique, illustre une métaphore de la lecture et donne lieu à un questionnement vertigineux sur les frontières entre réalité et fiction.

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

    Energy Technology Data Exchange (ETDEWEB)

    Littleton, Harry; Griffin, John


    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).

  19. Imaging Prostatic Lipids to Distinguish Aggressive Prostate Cancer (United States)


    Award Number: W81XWH-12-1-0168 TITLE: Imaging prostatic lipids to distinguish aggressive prostate cancer PRINCIPAL INVESTIGATOR: Jackilen...Imaging prostatic lipids to distinguish aggressive prostate Cancer 5a. CONTRACT NUMBER W81XWH-12-1-0168 5b. GRANT NUMBER PC110361 5c. PROGRAM...Mechanisms linking fatty acid synthase overexpression, lipid accumulation, lipid oxidation, and tumor aggressiveness will be explored using

  20. Understanding Prostate Cancer: Newly Diagnosed (United States)

    ... of Prostate Cancer Annual Report & Financials Our Leadership Leadership Team Board Members A Legacy of Leadership Featured Take ... Partners Faces of Prostate Cancer Annual Report & Financials Leadership Team Board Members Featured A Legacy of Leadership Take ...

  1. Medical Tests for Prostate Problems (United States)

    ... frequency—urination eight or more times a day urinary urgency—the inability to delay urination urinary incontinence—the ... prostatitis and another with BPH may both experience urinary urgency. Sometimes symptoms for the same prostate problem differ ...

  2. New Prostate Cancer Treatment Target (United States)

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

  3. Center for Prostate Disease Research (United States)

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

  4. Nasal tolerance with collagen v protein reverts bronchovascular axis remodeling in experimental bronchiolitis obliterans Tolerância nasal com a proteína colágeno V reverte o remodelamento no eixo broncovascular na bronquiolite obliterante experimental

    Directory of Open Access Journals (Sweden)

    Ana Garippo


    Full Text Available INTRODUCTION: The precise role of the remodeling process and possible therapies for bronchiolitis obliterans remain to be established. OBJETIVE: In the present study, we sought to validate the importance of nasal collagen V tolerance to verify whether bronchovascular axis remodeling could be reverted by this therapeutic approach when compared to steroid treatment. METHODS: Mice were randomly divided into 4 groups: control, bronchiolitis obliterans, collagen V tolerance, and prednisone groups. Morphometry was employed to evaluate bronchovascular axis dimensions, collagen density, and immune cell response. Collagen V nasal tolerance and steroid-treated mice showed significantly lower values of terminal bronchiole wall thickness and reduction in peribronchovascular cells; bronchioalveolar lymphoid tissue; and CD3+, CD4+, CD8+, and CD20+ lymphocytes. A significant decrease in CD68+ macrophage density was found in prednisone-treated mice. In addition, a strong quantitative relationship was found between collagen V tolerance, and reduction in density of immune cells and collagen. RESULTS: Our results indicate that bronchovascular axis remodeling in bronchiolitis obliterans can be reverted by collagen V nasal tolerance, possibly as the result of T-cell suppression. CONCLUSION: We concluded that the tolerance effects in this model were strongly related to the improvement in bronchovascular remodeling, and these may be an appropriate targets for further prospective studies on nasal collagen V tolerance.INTRODUÇÃO: A participação precisa do processo de remodelamento e possíveis implicações no tratamento da bronquiolite obliterante ainda não está estabelecida. OBJETIVOS: Estabelecer a importância da tolerância nasal induzida pelo colágeno do tipo V e verificar se o processo de remodelamento do eixo broncovascular pode ser revertido com esta estratégia terapêutica comparada ao efeito do tratamento com esteróides. MATERIAL E M

  5. Computed tomography of the prostate. (United States)

    Van Engelshoven, J M; Kreel, L


    The conventional anatomy of the prostate is reviewed and the computed tomography (CT) anatomy described and illustrated. The results of 55 "normal" cases were analyzed for size and relationship to the symphysis pubis, retropubic space, and bladder, as shown on CT sections correlating the features with age and possible urinary symptoms. Attention is also drawn to the differences between phleboliths and prostatic calcification. Computed tomography is an effective method of demonstrating the prostate and surrounding structures and of assessing prostatic enlargement.

  6. Molecular markers for prostate cancer.

    NARCIS (Netherlands)

    Reynolds, M.A.; Kastury, K.; Groskopf, J.; Schalken, J.A.; Rittenhouse, H.G.


    Serum PSA testing has been used for over 20 years as an aid in the diagnosis and management of prostate cancer. Although highly sensitive, it suffers from a lack of specificity, showing elevated serum levels in a variety of other conditions including prostatitis, benign prostate hyperplasia, and non

  7. Cholesterol and benign prostate disease. (United States)

    Freeman, Michael R; Solomon, Keith R


    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.

  8. Prostatic uptake of Ga-67

    Energy Technology Data Exchange (ETDEWEB)

    Sullivan, W.T.; Rosen, P.R.; Weiland, F.L.; Ritchey, M.L.


    Midline activity low in the pelvis seen on Ga-67 scans is frequently attributed to colonic excretion of radionuclide. Two cases of infectious prostatitis with focal uptake of Ga-67 within the prostate gland are described. A technique of using limited quantities of barium administered by enema and appropriate positional imaging, which localized pelvic activity to the prostate, is described.

  9. Utility of ADC measurement on diffusion-weighted MRI in differentiation of prostate cancer, normal prostate and prostatitis. (United States)

    Esen, Meltem; Onur, Mehmet Ruhi; Akpolat, Nusret; Orhan, Irfan; Kocakoc, Ercan


    To determine the utility of apparent diffusion coefficient (ADC) values in differentiation of prostate cancer from normal prostate parenchyma and prostatitis we obtained ADC values of 50 patients at b 100, 600 and 1,000 s/mm(2) diffusion gradients. The ADC values of prostate cancer group were significantly lower than normal prostate and prostatitis group at b 600 and 1,000 s/mm(2) gradients. The ADC values at high diffusion gradients may be used in differentiation prostate cancer from normal prostate and prostatitis.

  10. Calcium supplementation reverts central adiposity, leptin, and insulin resistance in adult offspring programed by neonatal nicotine exposure. (United States)

    Nobre, J L; Lisboa, P C; Santos-Silva, A P; Lima, N S; Manhães, A C; Nogueira-Neto, J F; Cabanelas, A; Pazos-Moura, C C; Moura, E G; de Oliveira, E


    Obesity is a worldwide epidemic. Calcium influences energy metabolism regulation, causing body weight loss. Because maternal nicotine exposure during lactation programs for obesity, hyperleptinemia, insulin resistance (IR), and hypothyroidism, we decided to evaluate the possible effect of dietary calcium supplementation on these endocrine dysfunctions in this experimental model. Osmotic minipumps containing nicotine solution (N: 6 mg/kg per day for 14 days) or saline (C) were s.c. implanted in lactating rats 2 days after giving birth (P2). At P120, N and C offspring were subdivided into four groups: 1) C - standard diet; 2) C with calcium supplementation (CCa, 10 g calcium carbonate/kg rat chow); 3) N - standard diet; and 4) N with calcium supplementation (NCa). Rats were killed at P180. As expected, N offspring showed higher visceral and total body fat, hyperleptinemia, lower hypothalamus leptin receptor (OB-R) content, hyperinsulinemia, and higher IR index. Also, higher tyrosine hydroxylase (TH) expression (+51%), catecholamine content (+37%), and serum 25-hydroxyvitamin D(3) (+76%) were observed in N offspring. Dietary calcium supplementation reversed adiposity, hyperleptinemia, OB-R underexpression, IR, TH overexpression, and vitamin D. However, this supplementation did not reverse hypothyroidism. In NCa offspring, Sirt1 mRNA was lower in visceral fat (-37%) and higher in liver (+42%). In conclusion, dietary calcium supplementation seems to revert most of the metabolic syndrome parameters observed in adult offspring programed by maternal nicotine exposure during lactation. It is conceivable that the reduction in fat mass per se, induced by calcium therapy, is the main mechanism that leads to the increment of insulin action.

  11. Integrated Proteomics and Genomics Analysis Reveals a Novel Mesenchymal to Epithelial Reverting Transition in Leiomyosarcoma through Regulation of Slug* (United States)

    Yang, Jilong; Eddy, James A.; Pan, Yuan; Hategan, Andrea; Tabus, Ioan; Wang, Yingmei; Cogdell, David; Price, Nathan D.; Pollock, Raphael E.; Lazar, Alexander J. F.; Hunt, Kelly K.; Trent, Jonathan C.; Zhang, Wei


    Leiomyosarcoma is one of the most common mesenchymal tumors. Proteomics profiling analysis by reverse-phase protein lysate array surprisingly revealed that expression of the epithelial marker E-cadherin (encoded by CDH1) was significantly elevated in a subset of leiomyosarcomas. In contrast, E-cadherin was rarely expressed in the gastrointestinal stromal tumors, another major mesenchymal tumor type. We further sought to 1) validate this finding, 2) determine whether there is a mesenchymal to epithelial reverting transition (MErT) in leiomyosarcoma, and if so 3) elucidate the regulatory mechanism responsible for this MErT. Our data showed that the epithelial cell markers E-cadherin, epithelial membrane antigen, cytokeratin AE1/AE3, and pan-cytokeratin were often detected immunohistochemically in leiomyosarcoma tumor cells on tissue microarray. Interestingly, the E-cadherin protein expression was correlated with better survival in leiomyosarcoma patients. Whole genome microarray was used for transcriptomics analysis, and the epithelial gene expression signature was also associated with better survival. Bioinformatics analysis of transcriptome data showed an inverse correlation between E-cadherin and E-cadherin repressor Slug (SNAI2) expression in leiomyosarcoma, and this inverse correlation was validated on tissue microarray by immunohistochemical staining of E-cadherin and Slug. Knockdown of Slug expression in SK-LMS-1 leiomyosarcoma cells by siRNA significantly increased E-cadherin; decreased the mesenchymal markers vimentin and N-cadherin (encoded by CDH2); and significantly decreased cell proliferation, invasion, and migration. An increase in Slug expression by pCMV6-XL5-Slug transfection decreased E-cadherin and increased vimentin and N-cadherin. Thus, MErT, which is mediated through regulation of Slug, is a clinically significant phenotype in leiomyosarcoma. PMID:20651304

  12. Construction and preliminary immunobiological characterization of a novel, non-reverting, intranasal live attenuated whooping cough vaccine candidate. (United States)

    Cornford-Nairns, Renee; Daggard, Grant; Mukkur, Trilochan


    We describe the construction and immunobiological properties of a novel whooping cough vaccine candidate, in which the aroQ gene, encoding 3-dehydroquinase, was deleted by insertional inactivation using the kanamycin resistance gene cassette and allelic exchange using a Bordetella suicide vector. The aroQ B. pertussis mutant required supplementation of media to grow but failed to grow on an unsupplemented medium. The aroQ B. pertussis mutant was undetectable in the trachea and lungs of mice at days 6 and 12 post-infection, respectively. Antigen-specific antibody isotypes IgG1 and IgG2a, were produced, and cell-mediated immunity [CMI], using interleukin-2 and interferon-gamma as indirect indicators, was induced in mice vaccinated with the aroQ B. pertussis vaccine candidate, which were substantially enhanced upon second exposure to virulent B. pertussis. Interleukin- 12 was also produced in the aroQ B. pertussis-vaccinated mice. On the other hand, neither IgG2a nor CMI-indicator cytokines were produced in DTaP-vaccinated mice, although the CMI-indicator cytokines became detectable post-challenge with virulent B. pertussis. Intranasal immunization with one dose of the aroQ B. pertussis mutant protected vaccinated mice against an intranasal challenge infection, with no pathogen being detected in the lungs of immunized mice by day 7 post-challenge. B. pertussis aroQ thus constitutes a safe, non-reverting, metabolite-deficient vaccine candidate that induces both humoral and cellmediated immune responses with potential for use as a single-dose vaccine in adolescents and adults, in the first instance, with a view to disrupting the transmission cycle of whooping cough to infants and the community.

  13. Angiogenic activity of breast cancer patients' monocytes reverted by combined use of systems modeling and experimental approaches.

    Directory of Open Access Journals (Sweden)

    Nicolas Guex


    Full Text Available Angiogenesis plays a key role in tumor growth and cancer progression. TIE-2-expressing monocytes (TEM have been reported to critically account for tumor vascularization and growth in mouse tumor experimental models, but the molecular basis of their pro-angiogenic activity are largely unknown. Moreover, differences in the pro-angiogenic activity between blood circulating and tumor infiltrated TEM in human patients has not been established to date, hindering the identification of specific targets for therapeutic intervention. In this work, we investigated these differences and the phenotypic reversal of breast tumor pro-angiogenic TEM to a weak pro-angiogenic phenotype by combining Boolean modelling and experimental approaches. Firstly, we show that in breast cancer patients the pro-angiogenic activity of TEM increased drastically from blood to tumor, suggesting that the tumor microenvironment shapes the highly pro-angiogenic phenotype of TEM. Secondly, we predicted in silico all minimal perturbations transitioning the highly pro-angiogenic phenotype of tumor TEM to the weak pro-angiogenic phenotype of blood TEM and vice versa. In silico predicted perturbations were validated experimentally using patient TEM. In addition, gene expression profiling of TEM transitioned to a weak pro-angiogenic phenotype confirmed that TEM are plastic cells and can be reverted to immunological potent monocytes. Finally, the relapse-free survival analysis showed a statistically significant difference between patients with tumors with high and low expression values for genes encoding transitioning proteins detected in silico and validated on patient TEM. In conclusion, the inferred TEM regulatory network accurately captured experimental TEM behavior and highlighted crosstalk between specific angiogenic and inflammatory signaling pathways of outstanding importance to control their pro-angiogenic activity. Results showed the successful in vitro reversion of such an

  14. Granulomatous prostatitis: a pitfall in MR imaging of prostatic carcinoma

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    Gevenois, P.A. [Dept. of Radiology, Cliniques Univ. de Bruxelles, Hopital Erasme (Belgium); Stallenberg, B. [Dept. of Radiology, Cliniques Univ. de Bruxelles, Hopital Erasme (Belgium); Sintzoff, S.A. [Dept. of Radiology, Cliniques Univ. de Bruxelles, Hopital Erasme (Belgium); Salmon, I. [Dept. of Pathology, Cliniques Univ. de Bruxelles, Hopital Erasme (Belgium); Regemorter, G. van [Dept. of Urology, Cliniques Univ. de Bruxelles, Hopital Erasme (Belgium); Struyven, J. [Dept. of Radiology, Cliniques Univ. de Bruxelles, Hopital Erasme (Belgium)


    Granulomatous prostatitis is an uncommon disease that can mimic prostatic carcinoma on both digital rectal examination and transrectal ultrasound. Four patients who underwent magnetic resonance imaging of the prostate had a histological diagnosis of granulomatous prostatitis; three of them had recent urinary tract infections. The other patient had an associated midline prostatic cyst and a focus of malignancy. T1- and T2-weighted spin-echo images were obtained in all cases. Peripheral zone lesions of decreased signal intensity, suggestive of carcinoma, were found in all four patients on T2-weighted images. Granulomatous prostatitis should be considered in the differential diagnosis of low signal intensity areas with prostatic magnetic resonance imaging. (orig.)

  15. Granulomatous prostatitis after intravesical immunotherapy mimicking prostate cancer. (United States)

    Białek, Waldemar; Rudzki, Sławomir; Iberszer, Paweł; Wronecki, Lech


    Intravesical immunotherapy with attenuated strains of Mycobacterium bovis is a widely used therapeutic option in patients with non-muscle-invasive transitional cell carcinoma of the bladder. A rare complication of intravesical therapy with the Bacillus Calmette-Guérin vaccine is granulomatous prostatitis, which due to increasing levels of prostate-specific antigen and abnormalities found in transrectal examination of the prostate may suggest concomitant prostate cancer. A case of extensive granulomatous prostatitis in a 61-year-old patient which occurred after the first course of a well-tolerated Bacillus Calmette-Guérin therapy is presented. Due to abnormalities found in rectal examination and an abnormal transrectal ultrasound image of the prostate with extensive infiltration mimicking neoplastic hyperplasia a core biopsy of the prostate was performed. Histopathological examination revealed inflammatory infiltration sites of tuberculosis origin.

  16. Chronic prostatitis: Current concepts

    Directory of Open Access Journals (Sweden)

    Ram Vaidyanathan


    Full Text Available Purpose: Chronic prostatitis (CP is a common condition. It causes significant suffering to the patients and constitutes a sizeable workload for the urologists. The purpose of this review is to describe the currently accepted concepts regarding the aspects of CP. Materials and Methods: Relevant papers on the epidemiology, etiology, diagnosis, evaluation and management of CP were identified through a search of MEDLINE using text terms "prostatitis", "chronic prostatitis" and "chronic pelvic pain syndrome". The list of articles thus obtained was supplemented by manual search of bibliographies of the identified articles and also by exploring the MEDLINE option "Related Articles". Results: The salient points of the relevant articles on each aspect of CP have been summarized in the form of a non-systematic narrative review. Conclusion: Chronic prostatitis is caused by a variety of infective and non-infective factors and is characterized by a rather long remitting and relapsing clinical course. The diagnosis is based on symptoms comprising pain and nonspecific urinary and/or ejaculatory disturbances and microbiological tests to localize bacteria and/or leucocytes in segmented urinary tract specimens. The contemporary classification was proposed by the National Institutes of Health/National Institute of Diabetes Digestive Kidney Diseases (NIH/NIDDK. National Institutes of Health - Chronic Prostatitis Symptom Index (NIH-CPSI is the patient evaluation tool used extensively in clinical practice and research. Management should be individualized, multimodal and of an appropriate duration.

  17. ETS rearrangements in prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Mark A Rubin


    Prostate cancer is a clinically and molecularly heterogeneous disease.Understanding the biologic underpinning of prostate cancer is necessary to best determine how biology is associated with the risk of disease progression and how this understanding might provide insight into the development of novel therapeutic approaches.The focus of this review is on the recently identified common ETS and non-ETS gene rearrangements in prostate cancer.Although multiple molecular alterations have been detected in prostate cancer,a basic understanding of gene fusion prostate cancer should help explain the clinical and biologic diversity,providing a rationale for a molecular subclassification of the disease.


    Directory of Open Access Journals (Sweden)

    E. N. Gorbunova


    Full Text Available The authors determined the detection rates of prostatic intraepithelial neoplasia (PIN in 2317 patients with benign prostatic hyperplasia (BPH and prostate cancer (PC; and those of chronic prostatitis and fibrosis in patients with PIN, BPH, or PC. There was no difference in median age between the groups. PC was found to be more concurrent with PIN 2 than with BPH. The severer inflammation or fibrosis is, more likely there is a concomitance with PIN 2 or PC. There is evidence for the theory of inflammation is a factor of carcinogenesis. Prostatic fibrosis may also initiate carcinogenesis.


    Directory of Open Access Journals (Sweden)

    E. N. Gorbunova


    Full Text Available The authors determined the detection rates of prostatic intraepithelial neoplasia (PIN in 2317 patients with benign prostatic hyperplasia (BPH and prostate cancer (PC; and those of chronic prostatitis and fibrosis in patients with PIN, BPH, or PC. There was no difference in median age between the groups. PC was found to be more concurrent with PIN 2 than with BPH. The severer inflammation or fibrosis is, more likely there is a concomitance with PIN 2 or PC. There is evidence for the theory of inflammation is a factor of carcinogenesis. Prostatic fibrosis may also initiate carcinogenesis.

  20. Transurethral resection of the prostate (TURP) - Series (image) (United States)

    An enlarged prostate gland compresses the urethra, causing problems with urination. Prostate enlargement is caused by prostate gland overgrowth (benign prostatic hypertrophy or hyperplasia) or in some cases, prostate cancer.

  1. Osteoporosis and prostate cancer

    DEFF Research Database (Denmark)

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


    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....... The study was approved by the local ethics committee. None of the patients had received prior androgen deprivation or osteoporosis treatment. Results. In total, 105 individuals were included. The mean age of the participants was 70 years (range 53-91 years, SD 6.3). The median prostate-specific antigen...

  2. Staging of prostate cancer. (United States)

    Cheng, Liang; Montironi, Rodolfo; Bostwick, David G; Lopez-Beltran, Antonio; Berney, Daniel M


    Prostatic carcinoma (PCa) is a significant cause of cancer morbidity and mortality worldwide. Accurate staging is critical for prognosis assessment and treatment planning for PCa. Despite the large volume of clinical activity and research, the challenge to define the most appropriate and clinically relevant staging system remains. The pathologically complex and uncertain clinical course of prostate cancer further complicates the design of staging classification and a substaging system suitable for individualized care. This review will focus on recent progress and controversial issues related to prostate cancer staging. The 2010 revision of the American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC) tumour, node and metastasis (TNM) system is the most widely used staging system at this time. Despite general acceptance of the system as a whole, there is controversy and uncertainty about its application, particularly for T2 subclassification. The three-tiered T2 classification system for organ-confined prostate cancer is superfluous, considering the biology and anatomy of PCa. A tumour size-based substaging system may be considered in the future TNM subclassification of pT2 cancer. Lymph node status is one of the most important prognostic factors for prostate cancer. Nevertheless, clinical outcomes in patients with positive lymph nodes are variable. Identification of patients at the greatest risk of systemic progression helps in the selection of appropriate therapy. The data suggest that the inherent aggressiveness of metastatic prostate cancer is closely linked to the tumour volume of lymph node metastasis. We recommend that a future TNM staging system should consider subclassification of node-positive cancer on the basis of nodal cancer volume, using the diameter of the largest nodal metastasis and/or the number of positive nodes.

  3. Prostatitis-bacterial - self-care (United States)

    ... this page: // Prostatitis- bacterial - self-care To use the sharing features ... enable JavaScript. You have been diagnosed with bacterial prostatitis . This is an infection of the prostate gland. ...

  4. Giant prostatic fossa with misleading radiographic features. (United States)

    Stenzl, A; Fuchs, G J


    The long-term complication of a perforation of the prostatic capsule during transurethral resection of the prostate is described. Calcifications in a giant prostatic fossa led to initially misleading radiologic findings.

  5. Ultrasound- and MRI-Guided Prostate Biopsy (United States)

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

  6. Enlarged prostate - what to ask your doctor (United States)

    What to ask your doctor about enlarged prostate; Benign prostatic hypertrophy - what to ask your doctor; BPH - what to ... . Roehrborn CG. Benign prostatic hyperplasia: Etiology, pathophysiology, epidemiology, and natural history. In: Wein ...

  7. Androgen and prostatic stroma

    Institute of Scientific and Technical Information of China (English)

    Yuan-JieNIU; Teng-XiangMA; IuZHANG; YongXU; Rui-FaHAN; GuangSUN


    Aim:To investigate the effect of androgen on the proliferation,differentiation and regression of canine prostatic stromal cells in vivo and human stromal cells in vitro.Methods:Twenty-two dogs,including 15 normal prostate doge and 7 prostatic hyperplasia dogs,had their serum concentration of testosterone and estrodiol determined by radioimmunoassay before and after castration.The expression of androgen receptor(AR)and estrogen receptor(ER)in the prostate were analysed by immunohistochemistry and semi-quantitative RT-PCR before and after castration.Light microscopy,transmission electron microscopy and TUNEL assay were carried out successively before and after castration to evaluate the prostatic histomorphology.In vitro serum-free cell cultures from human prostatic stroma were established and exposed to dihydrotestosterone(DHT).The proliferation of the cell culture was detected by MTT assay.The expression of TGFβ bFGF,AR,and smooth muscle cell(SMC) specific proteins (myosin and/or smoothelin)were detected using immunohistochemistry and RT-PCR.The differentiation from fibroblasts to smooth muscle cells was deduced by measuring the expression of SMC specific proteins.Results:Before castration,the serum concentrations of testosterone and estrodiol were not statistically different between normal and hyperplasia groups.Following castration,the serum concentration of testerone decreased rapidly in 2 days,and the concentration of estrodiol had no significant change compared with the pre-castration data.In the prostate,AR was presented in both the epithelial and stromal cells and the AR mRNA level was higher in hyperplasia than in normal prostate tissues(P<0.05).While ER predominantly existed in the prostate stromal cells and the ER mRNA had no difference between the hyperplasia and the normal group.Within the early phase of castration(

  8. Common Questions About Chronic Prostatitis. (United States)

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


    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

  9. A novel cryptic binding motif, LRSKSRSFQVSDEQY, in the C-terminal fragment of MMP-3/7-cleaved osteopontin as a novel ligand for α9β1 integrin is involved in the anti-type II collagen antibody-induced arthritis.

    Directory of Open Access Journals (Sweden)

    Shigeyuki Kon

    Full Text Available Osteopontin (OPN is a multifunctional protein that has been linked to various intractable inflammatory diseases. One way by which OPN induces inflammation is the production of various functional fragments by enzyme cleavage. It has been well appreciated that OPN is cleaved by thrombin, and/or matrix metalloproteinase-3 and -7 (MMP-3/7. Although the function of thrombin-cleaved OPN is well characterized, little is known about the function of MMP-3/7-cleaved OPN. In this study, we found a novel motif, LRSKSRSFQVSDEQY, in the C-terminal fragment of MMP-3/7-cleaved mouse OPN binds to α9β1 integrin. Importantly, this novel motif is involved in the development of anti-type II collagen antibody-induced arthritis (CAIA. This study provides the first in vitro and in vivo evidence that OPN cleavage by MMP-3/7 is an important regulatory mechanism for CAIA.

  10. Comparability of prostate trials

    DEFF Research Database (Denmark)

    Suciu, S; Sylvester, R; Iversen, P


    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...

  11. Enlarged prostate - after care (United States)

    ... . NcNicholas TA, Kirby RS, Lepor H. Evaluation and nonsurgical management of benign prostatic hyperplasia. In: Wein AJ, Kavoussi LR, Novick AC, Partin AW, Peters CA, eds. Campbell-Walsh Urology . 10th ed. Philadelphia, ...

  12. [Grading of prostate cancer]. (United States)

    Kristiansen, G; Roth, W; Helpap, B


    The current grading of prostate cancer is based on the classification system of the International Society of Urological Pathology (ISUP) following a consensus conference in Chicago in 2014. The foundations are based on the frequently modified grading system of Gleason. This article presents a brief description of the development to the current ISUP grading system.

  13. Benign Prostatic Hyperplasia (United States)

    ... prostate gets bigger, it may press on the urethra and cause the flow of urine to be slower and less forceful. "Benign" means the enlargement isn't caused by cancer or infection. "Hyperplasia" means enlargement. SymptomsWhat are the ...

  14. Proteoglycans in prostate cancer. (United States)

    Edwards, Iris J


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

  15. Interphase cytogenetics of prostatic adenocarcinoma


    Alers, Janneke


    textabstractIn the first part of this chapter an overview will be presented on the structural, histological and functional aspects of the normal human prostate. The second part describes the epidemiological and clinicopathological features of prostatic adenocarcinoma. Further, a state of the art of (cyto)genetic aberrations occurring in prostatic cancer is given. The third part of this introduction will discuss methodological aspects of this thesis, i.e., the development and methodology of no...

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

    DEFF Research Database (Denmark)

    Bødker, A; Bruun, J; Balslev, E


    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...... in the stroma, but in BPH specimens they can also be found in the glandular epithelium. Biochemically, the use of the DCC analysis is of limited value, since ER content in the human prostate and prostatic urethra is at the limit of detection with this method....

  17. Le livre au coeur du labyrinthe : Le Club Dumas ou l'ombre de Richelieu d'Arturo Pérez-Reverte


    Garcia, Marie-Thérèse


    Dans le Club Dumas ou l’ombre de Richelieu, l’écrivain Arturo Pérez-Reverte, fervent lecteur, rend un hommage ludique au Livre. Deux manuscrits sont au cœur de sa construction labyrinthique, nouent l’intrigue et surtout dessinent, révèlent et déterminent les personnages. Héros d’Alexandre Dumas et créatures romanesques, filles de Conan Doyle et de Jacques Cazotte envahissent la fiction, poursuivent le protagoniste et l’amènent aux limites du fantastique. Mêlant les structures génériques du ro...

  18. Reverted glutathione S-transferase-like genes that influence flower color intensity of carnation (Dianthus caryophyllus L.) originated from excision of a transposable element


    Momose, Masaki; Itoh, Yoshio; Umemoto, Naoyuki; Nakayama, Masayoshi; Ozeki, Yoshihiro


    A glutathione S-transferase-like gene, DcGSTF2, is responsible for carnation (Dianthus caryophyllus L.) flower color intensity. Two defective genes, DcGSTF2mu with a nonsense mutation and DcGSTF2-dTac1 containing a transposable element dTac1, have been characterized in detail in this report. dTac1 is an active element that produces reverted functional genes by excision of the element. A pale-pink cultivar ‘Daisy’ carries both defective genes, whereas a spontaneous deep-colored mutant ‘Daisy-V...

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

    Directory of Open Access Journals (Sweden)

    George Camara-Lopes


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

  20. Nonspecific Presentation of a Multiloculated Prostatic Abscess After Transurethral Prostatic Biopsy for Elevated Prostate-specific Antigen Level

    Directory of Open Access Journals (Sweden)

    Nilay M. Gandhi


    Full Text Available Prostate postbiopsy infectious complications typically present in the form of prostatitis and uncommonly urosepsis. Prostatic abscesses are generally found after multiple bouts of prostatitis and are associated with a clinically septic picture requiring intensive care unit admission and resuscitation. We report the case of a 65-year-old man who presented with prostatic abscess in the setting of nonspecific urinary symptoms after transrectal ultrasonography–guided prostate biopsy. At 4-month follow-up, he is currently free of disease with undetectable prostate-specific antigen level and negative imaging.

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

    NARCIS (Netherlands)

    Borren, A.


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

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

    DEFF Research Database (Denmark)

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


    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...

  3. Acupuncture Treatment of Prostatitis

    Institute of Scientific and Technical Information of China (English)

    HU Jin-sheng


    @@ 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.

  4. Chemotherapeutic prevention studies of prostate cancer

    DEFF Research Database (Denmark)

    Djavan, Bob; Zlotta, Alexandre; Schulman, Claude


    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....

  5. Prostate-specific antigen (PSA) blood test (United States)

    Prostate-specific antigen; Prostate cancer screening test; PSA ... special steps are needed to prepare for this test. ... Reasons for a PSA test: This test may be done to screen for prostate cancer. It is also used to follow people after prostate cancer ...

  6. Incidental fleurodeoxyglucose uptake in the prostate. (United States)

    Wong, W L; Moule, R N; Nunan, T


    This commentary confirms the rarity of prostatic cancer associated with incidental prostatic fleurodeoxyglucose (FDG) uptake. The study adds to the literature by showing that even if a prostate lesion is FDG avid it is unlikely to be due to cancer. The commentary considers the management of incidental prostate FDG uptake on the basis of the available evidence.

  7. Blood lipids and prostate cancer

    DEFF Research Database (Denmark)

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


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

  8. Imaging of recurrent prostate cancer

    NARCIS (Netherlands)

    Futterer, J.J.


    Approximately 30\\% of patients who underwent radical prostatectomy or radiation therapy will develop biochemical recurrent disease. Biochemical recurrent disease is defined as an increase in the serum value of prostate-specific antigen (PSA) after reaching the nadir. Prostate recurrence can present

  9. Biomarkers in Prostate Cancer Epidemiology

    Directory of Open Access Journals (Sweden)

    Mudit Verma


    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.


    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...

  11. Interphase cytogenetics of prostatic adenocarcinoma

    NARCIS (Netherlands)

    J.C. Alers (Janneke)


    textabstractIn the first part of this chapter an overview will be presented on the structural, histological and functional aspects of the normal human prostate. The second part describes the epidemiological and clinicopathological features of prostatic adenocarcinoma. Further, a state of the art of

  12. Genetic Analysis of Prostate Cancer

    NARCIS (Netherlands)

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


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

  13. Prostatic acid phosphatase by radioimmunoassay

    Energy Technology Data Exchange (ETDEWEB)

    Lindholm, G.R.; Stirton, M.S.; Liedtke, R.J.; Batjer, J.D.


    Prostatic acid phosphatase values in 98 patients with prostatic carcinoma were measured by a commmercial radioimmunoassay (RIA) and by enzymatic assay. Forty-three carcinomas were staged by rigorous pathological criteria. Patients (N = 129) with benign prostatic hyperplasia were the control group. At 94% specificity, sensitivities of the RIA vs the enzymatic assay for clinically staged patients were as follows: stage A, 22% vs 6%; B, 29% vs 10%; C, 52% vs 38%; and D, 87% vs 80%. However, none of the seven patients with pathological stage A and B disease had a positive test result, and we suggest that variability in staging criteria accounts for the discrepant sensitivity claims reported. Prostatic acid phosphatase RIA should not be used for screening but as an adjunct for staging known prostatic carcinoma.

  14. MAGI-2 in prostate cancer

    DEFF Research Database (Denmark)

    Goldstein, Jeffery; Borowsky, Alexander D; Goyal, Rajen;


    described in prostate cancer. We studied the immunohistochemical expression of MAGI-2 protein in prostate tissue. Seventy-eight radical prostatectomies were used to construct 3 tissue microarrays consisting of 512 cores, including benign tissue, benign prostatic hyperplasia, high-grade prostatic...... to distinguish benign tissue and adenocarcinoma, a receiver operating curve yielded an area under the curve of 0.902. A STAIN threshold of 1470 yielded a sensitivity of 0.66 and specificity of 0.96. There was a significant correlation between PTEN and MAGI-2 staining for normal and benign prostatic hyperplasia...... by %AREA (STAIN). By visual and image analysis, MAGI-2 was significantly higher in adenocarcinoma and HGPIN compared with benign (benign versus HGPIN P benign versus adenocarcinoma, P

  15. New drugs in prostate cancer

    Directory of Open Access Journals (Sweden)

    Sangjun Yoo


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

  16. A Prospective Randomized Trial of Two Different Prostate Biopsy Schemes (United States)


    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

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

    Directory of Open Access Journals (Sweden)

    Soleiman Mahjoub


    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.

  18. Role of CT in patients with prostatic disease; Usefulness of depiction of prostatic zonal anatomy

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    Yoshizako, Takeshi; Sugimura, Kazuro; Kaji, Yasushi; Moriyama, Masahiro; Ishida, Tetsuya (Shimane Medical Univ., Izumo (Japan))


    The purpose of this study was to evaluate the role of CT in patients with and without prostatic disease. CT and MR findings were reviewed in 25 patients without known prostatic disease, 11 patients with benign prostatic hyperplasia and 11 patients with prostatic cancer. Differential attenuation allowed for distinction of the peripheral zone and inner gland of the prostate by CT in 72% of normal patients. The distinction rate of prostatic zonal anatomy by CT decreased to 30% in the diseased group. When zonal anatomy of the prostate is not visualized on pelvic enhanced CT, the presence of prostatic disease might be considered. (author).

  19. Photoacoustic imaging of prostate brachytherapy seeds in ex vivo prostate (United States)

    Kuo, Nathanael; Kang, Hyun Jae; DeJournett, Travis; Spicer, James; Boctor, Emad


    The localization of brachytherapy seeds in relation to the prostate is a key step in intraoperative treatment planning (ITP) for improving outcomes in prostate cancer patients treated with low dose rate prostate brachytherapy. Transrectal ultrasound (TRUS) has traditionally been the modality of choice to guide the prostate brachytherapy procedure due to its relatively low cost and apparent ease of use. However, TRUS is unable to visualize seeds well, precluding ITP and producing suboptimal results. While other modalities such as X-ray and magnetic resonance imaging have been investigated to localize seeds in relation to the prostate, photoacoustic imaging has become an emerging and promising modality to solve this challenge. Moreover, photoacoustic imaging may be more practical in the clinical setting compared to other methods since it adds little additional equipment to the ultrasound system already adopted in procedure today, reducing cost and simplifying engineering steps. In this paper, we demonstrate the latest efforts of localizing prostate brachytherapy seeds using photoacoustic imaging, including visualization of multiple seeds in actual prostate tissue. Although there are still several challenges to be met before photoacoustic imaging can be used in the operating room, we are pleased to present the current progress in this effort.

  20. mPGES-1 in prostate cancer controls stemness and amplifies epidermal growth factor receptor-driven oncogenicity. (United States)

    Finetti, Federica; Terzuoli, Erika; Giachetti, Antonio; Santi, Raffaella; Villari, Donata; Hanaka, Hiromi; Radmark, Olof; Ziche, Marina; Donnini, Sandra


    There is evidence that an inflammatory microenvironment is associated with the development and progression of prostate cancer (PCa), although the determinants of intrinsic inflammation in PCa cells are not completely understood. Here we investigated whether expression of intrinsic microsomal PGE synthase-1 (mPGES-1) enhanced aggressiveness of PCa cells and might be critical for epidermal growth factor receptor (EGFR)-mediated tumour progression. In PCa, overexpression of EGFR promotes metastatic invasion and correlates with a high Gleason score, while prostaglandin E2 (PGE2) has been reported to modulate oncogenic EGFR-driven oncogenicity. Immunohistochemical studies revealed that mPGES-1 in human prostate tissues is correlated with EGFR expression in advanced tumours. In DU145 and PC-3 cell lines expressing mPGES-1 (mPGES-1(SC) cells), we demonstrate that silencing or 'knock down' of mPGES-1 (mPGES-1(KD)) or pharmacological inhibition by MF63 strongly attenuates overall oncogenic drive. Indeed, mPGES-1(SC) cells express stem-cell-like features (high CD44, β1-integrin, Nanog and Oct4 and low CD24 and α6-integrin) as well as mesenchymal transition markers (high vimentin, high fibronectin, low E-cadherin). They also show increased capacity to survive irrespective of anchorage condition, and overexpress EGFR compared to mPGES-1(KD) cells. mPGES-1 expression correlates with increased in vivo tumour growth and metastasis. Although EGFR inhibition reduces mPGES-1(SC) and mPGES-1(KD) cell xenograft tumour growth, we show that mPGES-1/PGE2 signalling sensitizes tumour cells to EGFR inhibitors. We propose mPGES-1 as a possible new marker of tumour aggressiveness in PCa.

  1. Prostate Artery Embolization for Benign Prostatic Hyperplasia: Current Status. (United States)

    Mirakhur, Anirudh; McWilliams, Justin P


    Prostate artery embolization has garnered much attention as a promising treatment for lower urinary tract symptoms secondary to benign prostatic hyperplasia. We aim to provide an up-to-date review of this minimally invasive technique, including discussion of potential benefits and technical challenges. Current evidence suggests it is a safe and effective option for patients with medication-refractory urinary obstructive symptoms who are poor surgical candidates or refuse surgical therapy. Larger, randomized studies with long-term follow-up data are needed for this technique to be formally established in the treatment paradigm for benign prostatic hyperplasia.

  2. A histological study of prostate

    Directory of Open Access Journals (Sweden)

    Ashfaq U. Hassan


    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. Targeting Prostate Cancer Metastasis (United States)


    AWARD NUMBER: W81XWH-14-1-0412 TITLE: "Targeting Prostate Cancer Metastasis " PRINCIPAL INVESTIGATOR: Yong Teng CONTRACTING ORGANIZATION: Prost a t e Cancer Metastasi s Sb. GRANT NUMBER W81XWH- 14- 1- 0 41 2 Sc. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Sd. PROJECT NUMBER YongTeng Se...r egulator in contr olling metastasis of p r ost a t e cancer and i nhi b i t i ng i t prevent s met ast asis . There are no drugs available to tar

  4. Comparability of prostate trials

    DEFF Research Database (Denmark)

    Suciu, S; Sylvester, R; Iversen, P;


    The present overview of advanced prostate cancer required the identification of randomized clinical trials studying the question of maximal androgen blockade versus the classic castration therapy. The heterogeneity of the trials concerned the type of castration (surgical or chemical) and the type...... of antiandrogen (flutamide, Anandron, or cyproterone acetate) added to castration. This paper reviews the different types of heterogeneity that might exist among trials that are involved in the overview: study design, randomization procedure, treatment evaluation, statistical evaluation, and data maturity...... with a larger number of patients and a longer follow-up will contribute more to the overview's results....

  5. Nebraska Prostate Cancer Research Program (United States)


    Annual National Symposium on Prostate Cancer by CCRTD, CAU, March 16-19, 2014. 15. Appendix #15: Peer- reviewed scientific publication with inputs...and  Immunology Y. Tu CU Regulation of G‐Protein‐Coupled  Receptors in Prostate  Cancer     Acknowledgements: DOD CDMRP PCa Research Program PC121645...AWARD NUMBER: W81XWH-13-1-0264 TITLE: Nebraska Prostate Cancer Research Program PRINCIPAL INVESTIGATOR: Ming-Fong Lin, Ph.D

  6. INaP selective inhibition reverts precocious inter- and motorneurons hyperexcitability in the Sod1-G93R zebrafish ALS model (United States)

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


    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

  7. Prostatic urethral lift vs transurethral resection of the prostate

    DEFF Research Database (Denmark)

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


    OBJECTIVES: To compare prostatic urethral lift (PUL) with transurethral resection of the prostate (TURP) with regard to symptoms, recovery experience, sexual function, continence, safety, quality of life, sleep and overall patient perception. PATIENTS AND METHODS: A total of 80 patients with lowe...... in statistically significant improvement in sleep. CONCLUSION: PUL was compared to TURP in a randomised, controlled study which further characterized both modalities so that care providers and patients can better understand the net benefit when selecting a treatment option....

  8. Creation of Mice Bearing a Partial Duplication of HPRT Gene Marked with a GFP Gene and Detection of Revertant Cells In Situ as GFP-Positive Somatic Cells.

    Directory of Open Access Journals (Sweden)

    Asao Noda

    Full Text Available It is becoming clear that apparently normal somatic cells accumulate mutations. Such accumulations or propagations of mutant cells are thought to be related to certain diseases such as cancer. To better understand the nature of somatic mutations, we developed a mouse model that enables in vivo detection of rare genetically altered cells via GFP positive cells. The mouse model carries a partial duplication of 3' portion of X-chromosomal HPRT gene and a GFP gene at the end of the last exon. In addition, although HPRT gene expression was thought ubiquitous, the expression level was found insufficient in vivo to make the revertant cells detectable by GFP positivity. To overcome the problem, we replaced the natural HPRT-gene promoter with a CAG promoter. In such animals, termed HPRT-dup-GFP mouse, losing one duplicated segment by crossover between the two sister chromatids or within a single molecule of DNA reactivates gene function, producing hybrid HPRT-GFP proteins which, in turn, cause the revertant cells to be detected as GFP-positive cells in various tissues. Frequencies of green mutant cells were measured using fixed and frozen sections (liver and pancreas, fixed whole mount (small intestine, or by means of flow cytometry (unfixed splenocytes. The results showed that the frequencies varied extensively among individuals as well as among tissues. X-ray exposure (3 Gy increased the frequency moderately (~2 times in the liver and small intestine. Further, in two animals out of 278 examined, some solid tissues showed too many GFP-positive cells to score (termed extreme jackpot mutation. Present results illustrated a complex nature of somatic mutations occurring in vivo. While the HPRT-dup-GFP mouse may have a potential for detecting tissue-specific environmental mutagens, large inter-individual variations of mutant cell frequency cause the results unstable and hence have to be reduced. This future challenge will likely involve lowering the

  9. Reverted glutathione S-transferase-like genes that influence flower color intensity of carnation (Dianthus caryophyllus L.) originated from excision of a transposable element. (United States)

    Momose, Masaki; Itoh, Yoshio; Umemoto, Naoyuki; Nakayama, Masayoshi; Ozeki, Yoshihiro


    A glutathione S-transferase-like gene, DcGSTF2, is responsible for carnation (Dianthus caryophyllus L.) flower color intensity. Two defective genes, DcGSTF2mu with a nonsense mutation and DcGSTF2-dTac1 containing a transposable element dTac1, have been characterized in detail in this report. dTac1 is an active element that produces reverted functional genes by excision of the element. A pale-pink cultivar 'Daisy' carries both defective genes, whereas a spontaneous deep-colored mutant 'Daisy-VPR' lost the element from DcGSTF2-dTac1. This finding confirmed that dTac1 is active and that the resulting reverted gene, DcGSTF2rev1, missing the element is responsible for this color change. Crosses between the pale-colored cultivar '06-LA' and a deep-colored cultivar 'Spectrum' produced segregating progeny. Only the deep-colored progeny had DcGSTF2rev2 derived from the 'Spectrum' parent, whereas progeny with pale-colored flowers had defective forms from both parents, DcGSTF2mu and DcGSTF2-dTac1. Thus, DcGSTF2rev2 had functional activity and likely originated from excision of dTac1 since there was a footprint sequence at the vacated site of the dTac1 insertion. Characterizing the DcGSTF2 genes in several cultivars revealed that the two functional genes, DcGSTF2rev1 and DcGSTF2rev2, have been used for some time in carnation breeding with the latter in use for more than half a century.

  10. Dystrophic calcification of the prostate after cryotherapy. (United States)

    Dru, Christopher; Bender, Leon


    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.

  11. Understanding your prostate cancer risk (United States)

    Skip navigation U.S. National Library of Medicine The navigation menu has been collapsed. ... // Understanding your prostate cancer risk To use the sharing features ...

  12. Prostatic carcinosarcoma with lung metastases. (United States)

    Furlan, Stefanie R; Kang, David J; Armas, Armando


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

  13. Neuroendocrine differentiation in prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Jiaoti Huang


    @@ 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.

  14. ESUR prostate MR guidelines 2012

    DEFF Research Database (Denmark)

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


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

  15. Prostatic Carcinosarcoma with Lung Metastases

    Directory of Open Access Journals (Sweden)

    Stefanie R. Furlan


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

  16. Drugs Approved for Prostate Cancer (United States)

    ... 2015 2014 2013 2012 Media Resources Media Contacts Multicultural ... This page lists cancer drugs approved by the Food and Drug Administration (FDA) for prostate cancer. The list includes generic ...

  17. Multiparametric MR imaging in diagnosis of chronic prostatitis and its differentiation from prostate cancer

    Directory of Open Access Journals (Sweden)

    Vivek Kumar Sah


    Full Text Available Chronic prostatitis is a heterogeneous condition with high prevalence rate. Chronic prostatitis has overlap in clinical presentation with other prostate disorders and is one of the causes of high serum prostate specific antigen (PSA level. Chronic prostatitis, unlike acute prostatitis, is difficult to diagnose reliably and accurately on the clinical grounds alone. Not only this, it is also challenging to differentiate chronic prostatitis from prostate cancer with imaging modalities like TRUS and conventional MR Imaging, as the findings can mimic those of prostate cancer. Even biopsy doesn't play promising role in the diagnosis of chronic prostatitis as it has limited sensitivity and specificity. As a result of this, chronic prostatitis may be misdiagnosed as a malignant condition and end up in aggressive surgical management resulting in increased morbidity. This warrants the need of reliable diagnostic tool which has ability not only to diagnose it reliably but also to differentiate it from the prostate cancer. Recently, it is suggested that multiparametric MR Imaging of the prostate could improve the diagnostic accuracy of the prostate cancer. This review is based on the critically published literature and aims to provide an overview of multiparamateric MRI techniques in the diagnosis of chronic prostatitis and its differentiation from prostate cancer.

  18. Prostate cancer, prostate cancer death, and death from other causes, among men with metabolic aberrations.


    Häggström, Christel; Stocks, Tanja; Nagel, Gabriele; Manjer, Jonas; Bjørge, Tone; Hallmans, Göran; Engeland, Anders; Ulmer, Hanno; Lindkvist, Björn; Selmer, Randi; Concin, Hans; Tretli, Steinar; Jonsson, Håkan; Stattin, Pär


    Few previous studies of metabolic aberrations and prostate cancer risk have taken into account the fact that men with metabolic aberrations have an increased risk of death from causes other than prostate cancer. The aim of this study was to calculate, in a real-life scenario, the risk of prostate cancer diagnosis, prostate cancer death, and death from other causes.

  19. Solitary Fibrous Tumor of the Prostate Which Was Initially Misdiagnosed as Prostate Cancer (United States)

    Osamu, Soma; Murasawa, Hiromi; Yoneyama, Takahiro; Koie, Takuya; Ohyama, Chikara


    Solitary fibrous tumor (SFT) of the prostate is a very rare tumor. We report a case of 65-year-old man with SFT of the prostate which was initially misdiagnosed as prostate cancer. Finally, we performed total prostatectomy and the tumor was histologically diagnosed as SFT of the prostate. The patient's clinical course has progressed favorably with no obvious recurrence 18 months postoperatively.

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

    NARCIS (Netherlands)

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


    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,

  1. VEGF and prostatic cancer: a systematic review. (United States)

    Botelho, Francisco; Pina, Francisco; Lunet, Nuno


    Elevated vascular endothelial growth factor (VEGF) blood concentration reflects its prostatic production, making this a potentially interesting tumour marker to support the decision of submitting a patient for prostatic biopsy. The objective was to review systematically the evidence on the role of VEGF blood concentration in prostate cancer detection. Published studies addressing the relation between serum or plasma VEGF levels and prostate cancer were identified by searching Pubmed, ISI Web of Knowledge, SCOPUS and LILACS up to January 2010, and reviewed following a standardized protocol. Three studies reported higher plasma VEGF (pg/ml) in patients with localized prostate cancer than in healthy controls (7.0 vs. 0.0, 9.9 vs. 2.2, and 210 vs. 26.5, Pprostate cancer patients than in patients with benign prostate hypertrophy (518.9 vs. 267.9, Pbenign prostate hypertrophy, localized or metastatic prostate cancer. The three studies that used controls with previous suspicion of prostatic cancer but a negative biopsy reported non-statistically significant difference in VEGF serum levels (pg/ml) between controls and localized prostate cancer patients (241 vs. 206; 69.5 vs. 55; 215.2 vs. 266.4). Higher VEGF plasma levels are observed in prostatic cancer patients compared with healthy controls, but serum levels do not appear to be useful in differentiating benign from malignant prostatic disease using, as controls, individuals with high risk of prostate cancer and negative biopsy.

  2. Biomarkers in Prostate Cancer Epidemiology


    Mudit Verma; Mukesh Verma; Payal Patel


    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 ris...

  3. Nebraska Prostate Cancer Research Program (United States)


    MacDonald, Richard G; Mehta, Parmender P; Mott, Justin L; Naslavsky, Naava; Palanimuthu Ponnusamy, Moorthy; Ramaley, Robert F; Sorgen, Paul L; regulation of PI3K and androgen receptor signaling in PTEN-deficient prostate cancer, Cancer Cell 19 (2011) 575–586. [29] B.J. Feldman , D... Feldman , The development of androgen-independent prostate cancer, Nat. Rev. Cancer 1 (2001) 34–45. [30] J.D. Debes, D.J. Tindall, Mechanisms of androgen

  4. Cyclooxygenase-2 and prostate carcinogenesis. (United States)

    Hussain, Tajamul; Gupta, Sanjay; Mukhtar, Hasan


    In recent years a dramatic surge has occurred on studies defining to the role of cyclooxygenase (COX)-2 in causation and prevention of cancer. Prostaglandin (PG) endoperoxidase synthase also commonly referred to as COX is a key enzyme involved in the conversion of arachidonic acid to PGs and other eicosanoids. COX exists as two isoforms, namely COX-1 and COX-2 with distinct tissue distribution and physiological functions. COX-1 is constitutively expressed in many tissues and cell types and is involved in normal cellular physiological functions whereas COX-2 is pro-inflammatory in nature and is inducible by mitogens, cytokines, tumor promoters and growth factors. A large volume of data exists showing that COX-2 is overexpressed in a large number of human cancers and cancer cell lines. The possibility of COX-2 as a candidate player in cancer development and progression evolved from the epidemiological studies which suggest that regular use of aspirin or other non-steroidal anti-inflammatory drugs could significantly decrease the risk of developing cancers in experimental animals and in humans. In our recently published study (Prostate, 42 2000 73-78), we provided the first evidence that COX-2 is overexpressed in human prostate adenocarcinoma. Many other studies verified our initial observation and reported that compared to normal tissue, COX-2 is overexpressed in human prostate cancer. It should be noted that some recent work has suggested that COX-2 is only up-regulated in proliferative inflammatory atrophy of the prostate, but not in prostate carcinoma. In this scenario, COX-2 inhibitors could afford their effects against prostate carcinogenesis by modulating COX-2 activity in other cells in prostate. An exciting corollary to this ongoing work is that selective COX-2 inhibitors may exhibit chemopreventive and even chemotherapeutic effects against prostate carcinogenesis in humans.

  5. Prostate cancer in Latin America. (United States)

    Pow-Sang, Mariela; Destefano, Víctor; Astigueta, Juan Carlos; Castillo, Octavio; Gaona, José Luis; Santaella, Félix; Sotelo, Rene


    There is a very low rate of early prostate cancer detection in Latin America, since patients usually are diagnosed when the disease is in advanced stages. Sporadic prostate cancer screening campaigns do exist which allow us to diagnose this disease in earlier stages. Incidence and mortality rates differ widely from country to country, and they are probable underreported in our region since registers may be city-based instead of country-based.

  6. Review of Prostate Anatomy and Embryology and the Etiology of Benign Prostatic Hyperplasia. (United States)

    Aaron, LaTayia; Franco, Omar E; Hayward, Simon W


    Prostate development follows a common pattern between species and depends on the actions of androgens to induce and support ductal branching morphogenesis of buds emerging from the urogenital sinus. The human prostate has a compact zonal anatomy immediately surrounding the urethra and below the urinary bladder. Rodents have a lobular prostate with lobes radiating away from the urethra. The human prostate is the site of benign hyperplasia, prostate cancer, and prostatitis. The rodent prostate has little naturally occurring disease. Rodents can be used to model aspects of human benign hyperplasia, but care should be taken in data interpretation and extrapolation to the human condition.

  7. The role of prostatitis in prostate cancer: meta-analysis.

    Directory of Open Access Journals (Sweden)

    Junyi Jiang

    Full Text Available OBJECTIVE: Use systematic review methods to quantify the association between prostatitis and prostate cancer, under both fixed and random effects model. EVIDENCE ACQUISITION: Case control studies of prostate cancer with information on prostatitis history. All studies published between 1990-2012, were collected to calculate a pooled odds ratio. SELECTION CRITERIA: the selection criteria are as follows: human case control studies; published from May 1990 to July 2012; containing number of prostatitis, and prostate cancer cases. EVIDENCE SYNTHESIS: In total, 20 case control studies were included. A significant association between prostatitis and prostate cancer was found, under both fixed effect model (pooled OR=1.50, 95%CI: 1.39-1.62, and random effects model (OR=1.64, 95%CI: 1.36-1.98. Personal interview based case control studies showed a high level of association (fixed effect model: pooled OR=1.59, 95%CI: 1.47-1.73, random effects model: pooled OR= 1.87, 95%CI: 1.52-2.29, compared with clinical based studies (fixed effect model: pooled OR=1.05, 95%CI: 0.86-1.28, random effects model: pooled OR= 0.98, 95%CI: 0.67-1.45. Additionally, pooled ORs, were calculated for each decade. In a fixed effect model: 1990's: OR=1.58, 95% CI: 1.35-1.84; 2000's: OR=1.59, 95% CI: 1.40-1.79; 2010's: OR=1.37, 95% CI: 1.22-1.56. In a random effects model: 1990's: OR=1.98, 95% CI: 1.08-3.62; 2000's: OR=1.64, 95% CI: 1.23-2.19; 2010's: OR=1.34, 95% CI: 1.03-1.73. Finally a meta-analysis stratified by each country was conducted. In fixed effect models, U.S: pooled OR =1.45, 95%CI: 1.34-1.57; China: pooled OR =4.67, 95%CI: 3.08-7.07; Cuba: pooled OR =1.43, 95%CI: 1.00-2.04; Italy: pooled OR =0.61, 95%CI: 0.13-2.90. In random effects model, U.S: pooled OR=1.50, 95%CI: 1.25-1.80; China: pooled OR =4.67, 95%CI: 3.08-7.07; Cuba: pooled OR =1.43, 95%CI: 1.00-2.04; Italy: pooled OR =0.61, 95%CI: 0.13-2.90. CONCLUSIONS: the present meta-analysis provides the statistical

  8. Immunotherapy in metastatic prostate cancer (United States)

    Slovin, Susan F.


    Introduction: Prostate cancer remains a challenge as a target for immunological approaches. The approval of the first cell-based immune therapy, Sipuleucel-T for prostate cancer introduced prostate cancer as a solid tumor with the potential to be influenced by the immune system. Methods: We reviewed articles on immunological management of prostate cancer and challenges that lie ahead for such strategies. Results: Treatments have focused on the identification of novel cell surface antigens thought to be unique to prostate cancer. These include vaccines against carbohydrate and blood group antigens, xenogeneic and naked DNA vaccines, and pox viruses used as prime-boost or checkpoint inhibitors. No single vaccine construct to date has resulted in a dramatic antitumor effect. The checkpoint inhibitor, anti-CTLA-4 has resulted in several long-term remissions, but phase III trials have not demonstrated an antitumor effect or survival benefit. Conclusions: Multiple clinical trials suggest that prostate cancer may not be optimally treated by single agent immune therapies and that combination with biologic agents, chemotherapies, or radiation may offer some enhancement of benefit. PMID:27843208

  9. Immunotherapy in metastatic prostate cancer

    Directory of Open Access Journals (Sweden)

    Susan F Slovin


    Full Text Available Introduction: Prostate cancer remains a challenge as a target for immunological approaches. The approval of the first cell-based immune therapy, Sipuleucel-T for prostate cancer introduced prostate cancer as a solid tumor with the potential to be influenced by the immune system. Methods: We reviewed articles on immunological management of prostate cancer and challenges that lie ahead for such strategies. Results: Treatments have focused on the identification of novel cell surface antigens thought to be unique to prostate cancer. These include vaccines against carbohydrate and blood group antigens, xenogeneic and naked DNA vaccines, and pox viruses used as prime-boost or checkpoint inhibitors. No single vaccine construct to date has resulted in a dramatic antitumor effect. The checkpoint inhibitor, anti-CTLA-4 has resulted in several long-term remissions, but phase III trials have not demonstrated an antitumor effect or survival benefit. Conclusions: Multiple clinical trials suggest that prostate cancer may not be optimally treated by single agent immune therapies and that combination with biologic agents, chemotherapies, or radiation may offer some enhancement of benefit.

  10. Zonal differences in prostate diseases

    Institute of Scientific and Technical Information of China (English)

    JIANG Qi; XIA Shu-jie


    Regardless of its relatively small size,the prostate is the most common site of pathology in human male,1,2 and the prostate is the site of the two most frequent medical problems affecting elderly men,benign prostatic hyperplasia (BPH) and prostate cancer (PCa).Using the urethra as the key anatomical reference point,the prostate is conventionally divided into three distinct zones:peripheral zone,transition zone,and central zone.2This morphology is of clinical significance in the development of age-associated conditions such as BPH and PCa.3 Each of these zones exhibit a specific susceptibility to pathology,PCa develops mainly in the peripheral zone,whereas BPH occurs almost exclusively in the transition zone,whilst the central zone remains mostly disease-free.2,4,5 The functional basis and molecular mechanisms underlying these differences in disease susceptibility between the zones of the human prostate are unknown.Some of the differences in susceptibility to disease may have an embryological basis.

  11. Ureteral metastasis from prostate cancer. (United States)

    Hongo, Hiroshi; Kosaka, Takeo; Yoshimine, Shunsuke; Oya, Mototsugu


    A 59-year-old man had an elevated prostate-specific antigen (PSA) concentration (439 ng/mL) in December 2008. We diagnosed prostatic adenocarcinoma by prostate needle biopsy. CT and MRI showed a prostatic tumour with bone and lymph node metastases. Combined androgen blockade therapy reduced the PSA level temporarily. After the PSA level gradually started to increase again and reached 27.27 ng/mL in October 2010, the patient was diagnosed with castration-resistant prostate cancer and treated with docetaxel chemotherapy. Radiological examination detected left hydronephrosis and a tumour in the left lower ureter in March 2011. Retrograde pyelography and urine cytology of class 3 from the left ureter indicated that the ureteral mass was a urothelial carcinoma. A left nephroureterectomy was performed. After the operation, the pathological examination showed a metastatic prostate carcinoma, accompanied by a decrease in the serum PSA level from 59.56 to 45.33 ng/mL.

  12. Immunohistochemical Analysis of Omi/HtrA2 Expression in Prostate Cancer and Benign Prostatic Hyperplasia

    Institute of Scientific and Technical Information of China (English)

    HU Xiaoyong; CHEN Xiaochun; PING Hao; CHEN Zhaohui; ZENG Fuqing; LU Gongcheng


    To study the expression and significance of the serine protease Omi/HtrA2 in prostate cancer and benign prostatic hyperplasia. The expression of Omi/HtrA2 was assayed by means of immunohistochemical technique in 41 prostate cancer (Cap), 20 benign prostatic hyperplasia (BPH) and 10 normal prostate (NP) specimens. Omi/HtrA2 expression was positive in 30 (73.17%) prostate cancer specimens, and the positive rate of Omi/HtrA2 was lower in well differentiated than in poorly and moderately differentiated groups (P<0.05). By contrast, the cells in normal prostate and benign prostatic hyperplasia groups showed no or weak expression of Omi/HtrA2.Prostate cancer cells in vivo may need Omi/HtrA2 expression for apoptosis, and that Omi/HtrA2expression might be involved in prostate cancer development.

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

    Energy Technology Data Exchange (ETDEWEB)

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


    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.

  14. Xanthogranulomatous prostatitis: Rare presentation of rare disease

    Directory of Open Access Journals (Sweden)

    Rohan S Valsangkar


    Full Text Available Granulomatous inflammation of the prostate is a rare type of inflammation of the prostate. It is of various types, with the non-specific type of granulomatous inflammation being the most common. Xanthogranulomatous prostatitis is a rare type of granulomatous prostatitis of which very few cases have been reported. Histologically it is characterized by the presence of pale-looking foamy macrophages. It can be an incidental finding after transurethral resection of the prostate (TURP, although it may mimic prostatic malignancy clinically, biochemically, and rarely histologically. We report a rare case of xanthogranulomatous prostatitis which presented as a prostatic abscess, a presentation never reported in literature so far. The patient was managed with TURP.

  15. Alcohol May Fuel Prostate Cancer Risk (United States)

    ... page: Alcohol May Fuel Prostate Cancer Risk The more men ... and Australian scientists found a significant association between alcohol and prostate cancer risk, though they did not ...

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

    NARCIS (Netherlands)

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


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

  17. A case of giant prostatic hyperplasia


    Luke Wang; Paul Davis; Kevin McMillan


    Benign prostatic hyperplasia (BPH) is one of the most common conditions experienced by aging males and a frequent cause of bladder outlet obstruction and macroscopic haematuria. Giant prostatic hyperplasia (GPH) is an extremely rare form of prostatic hyperplasia. We present a case of a patient with GPH of 800 mL. To our knowledge, this is the fourth largest prostatic hyperplasia ever reported in the literature.

  18. Oxidative stress in prostate hyperplasia and carcinogenesis


    Udensi K. Udensi; Tchounwou, Paul B.


    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 a...

  19. Potential Prognostic Markers for Human Prostate Cancer (United States)


    Prostate 35: 185-192, 1998 osteoblasts on prostate carcinoma proliferation and chemo- 32. Trikha M, Cai Y, Grignon D, Honn KV: Identification taxis ...Markers for Human Prostate Cancer PRINCIPAL INVESTIGATOR: Bruce R. Zetter, Ph.D. CONTRACTING ORGANIZATION: Children’s Hospital Boston, Massachusetts...March 2001 Final (1 Sep 98 - 28 Feb 01) 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS Potential Prognostic Markers for Human Prostate Cancer DAMD17-98-1

  20. A case of giant prostatic hyperplasia

    Directory of Open Access Journals (Sweden)

    Luke Wang


    Full Text Available Benign prostatic hyperplasia (BPH is one of the most common conditions experienced by aging males and a frequent cause of bladder outlet obstruction and macroscopic haematuria. Giant prostatic hyperplasia (GPH is an extremely rare form of prostatic hyperplasia. We present a case of a patient with GPH of 800 mL. To our knowledge, this is the fourth largest prostatic hyperplasia ever reported in the literature.

  1. Diagnosis and treatment for prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Zuoxing Niu; Guohua Ren; Shuping Song


    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.

  2. Epidermal growth factor in the rat prostate

    DEFF Research Database (Denmark)

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


    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....

  3. Magnetic resonance imaging of the prostate

    DEFF Research Database (Denmark)

    Iversen, P; Kjaer, L; Thomsen, C


    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....

  4. BCG induced granulomatous prostatitis ; a case report

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Min Hoan; Seong, Chang Kyu; Lee, Kyoung Ho; Kim, Seung Hyup [College of Medicine and the Institute of Radiation Medicine, Seoul National University, Seoul (Korea, Republic of)


    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

    DEFF Research Database (Denmark)

    Iversen, P; Kjaer, L; Thomsen, C


    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. What Do Prostate Cancer Patients Die Of?


    Riihimäki, Matias; Thomsen, Hauke; Brandt, Andreas; Sundquist, Jan; Hemminki, Kari


    The cause of death in prostate cancer patients is examined using the Swedish Family-Cancer Database. Prostate cancer patients were found to have a higher risk for dying from various causes other than prostate cancer, including external causes and heart failure.

  7. Prostatic Adenosquamous Carcinoma Metastasizing to Testis

    Directory of Open Access Journals (Sweden)

    Dilek Ertoy Baydar


    Full Text Available Adenosquamous carcinoma of the prostate is an unusual tumor with poor prognosis. Most arise after hormonal or radiotherapy of conventional prostatic adenocarcinoma. Sarcomatous transformation in them has been reported in only a few cases. Here, we present a unique case of “de novo prostatic adenosquamous carcinoma with focal sarcomatoid areas” that showed testicular metastasis, detected after scrotal orchiectomy.

  8. Constitutional characteristics of zones of prostate structure

    Directory of Open Access Journals (Sweden)

    Vinnik Y.Y.


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

  9. Low Risk Prostate Cancer and Active Surveillance

    NARCIS (Netherlands)

    M. Bul (Meelan)


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

  10. Prevention and early detection of prostate cancer

    NARCIS (Netherlands)

    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)


    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

  11. Characterization of prostate cancer, benign prostatic hyperplasia and normal prostates using transrectal 31phosphorus magnetic resonance spectroscopy: a preliminary report

    Energy Technology Data Exchange (ETDEWEB)

    Narayan, P.; Jajodia, P.; Kurhanewicz, J.; Thomas, A.; MacDonald, J.; Hubesch, B.; Hedgcock, M.; Anderson, C.M.; James, T.L.; Tanagho, E.A. (Univ. of California School of Medicine, San Francisco (USA))


    We assessed the ability of 31phosphorus (31P) transrectal magnetic resonance spectroscopy to characterize normal human prostates as well as prostates with benign and malignant neoplasms. With a transrectal probe that we devised for surface coil spectroscopy we studied 15 individuals with normal (5), benign hyperplastic (4) and malignant (6) prostates. Digital rectal examination, transrectal ultrasonography and magnetic resonance imaging were used to aid in accurate positioning of the transrectal probe against the region of interest within the prostate. The major findings of the in vivo studies were that normal prostates had phosphocreatine-to-adenosine triphosphate (ATP) ratios of 1.2 +/- 0.2, phosphomonoester-to-beta-ATP ratios of 1.1 +/- 0.1 and phosphomonoester-to-phosphocreatine ratios of 0.9 +/- 0.1. Malignant prostates had phosphocreatine-to-beta-ATP ratios that were lower (0.7 +/- 0.1) than those of normal prostates (p less than 0.02) or prostates with benign hyperplasia. Malignant prostates had phosphomonoester-to-beta-ATP ratios (1.8 +/- 0.2) that were higher than that of normal prostates (p less than 0.02). Using the phosphomonoester-to-phosphocreatine ratio, it was possible to differentiate metabolically malignant (2.7 +/- 0.3) from normal prostates (p less than 0.001), with no overlap of individual ratios. The mean phosphomonoester-to-phosphocreatine ratio (1.5 +/- 0.5) of prostates with benign hyperplasia was midway between the normal and malignant ratios, and there was overlap between individual phosphomonoester-to-phosphocreatine ratios of benign prostatic hyperplasia glands with that of normal and malignant glands. To verify the in vivo results, we performed high resolution magnetic resonance spectroscopy on perchloric acid extracts of benign prostatic hyperplasia tissue obtained at operation and on a human prostatic cancer cell line DU145.

  12. Prostate specific antigen levels following transurethral resection of the prostate

    Directory of Open Access Journals (Sweden)

    Roberto C. Fonseca


    Full Text Available OBJECTIVE: Determine how serum prostate-specific antigen (t-PSA levels and free PSA (f/t PSA ratio change following transurethral resection of the prostate (TURP. MATERIALS AND METHODS: Thirty men with a mean age of 67.0 + 4.2 years (range 46 to 84 years underwent TURP for BPH between May 2005 and October 2005. Preoperative assessment included symptom evaluation with the International Prostate Symptom Score (I-PSS and the prostate volume estimation by transrectal ultrasound. Total PSA and f/t PSA ratio were assessed before the procedure, as well as 30, 60 and 180 days after the TURP. RESULTS: Clinical improvement after TURP, reflected by I-PSS score, was demonstrated as early as 30 days and remained stable until the end of the follow-up. Mean t-PSA declined 71% after TURP and 60 days after surgery the reduction reached its peak, stabilizing afterwards. It varied from 6.19 + 7.06 ng/mL before surgery to 1.75 + 1.66 ng/mL on day 60 (p < 0.001. The mean baseline f/t PSA ratio was 18.2% + 3.4% and was not significantly changed at any given time point in the postoperative period (p = 0.91. There were also no statistically significant differences in t-PSA or f/t PSA between patients with and without prostatitis at any time point (p = 0.23. Resected prostate fragments weighed 29.9 + 19.6 g, corresponding to 39.1% of the estimated preoperative prostate volume. Each gram of tissue resected decreased PSA by 0.15 + 0.11 ng/mL, while 1% prostate volume resected led to a reduction of 2.4% + 0.4% in serum PSA from baseline. CONCLUSIONS: PSA decreases drastically in patients who undergo TURP. These low levels stabilize within 60 days after surgery. The f/t PSA ratio did not change, and the finding of chronic prostatitis did not affect the levels of these variables.

  13. Contact laser vaporization of the prostate for benign prostatic hypertrophy (United States)

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


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

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

  15. Prostate cancer incidence in men with self-reported prostatitis after 15 years of follow-up. (United States)

    Vaarala, Markku H; Mehik, Aare; Ohtonen, Pasi; Hellström, Pekka A


    Controversy exists regarding a possible association between prostatitis and prostate cancer. To further evaluate the incidence of prostate cancer following prostatitis, a study of prostate cancer incidence in a cohort of Finnish men was performed. The original survey evaluating self-reported prostatitis was conducted in 1996-1997. A database review was conducted focusing on prostate cancer diagnoses in the cohort. In 2012, there were 13 (5.2%) and 27 (1.8%) prostate cancer cases among men with (n=251) and without (n=1,521) prostatitis symptoms, respectively. There were no significant differences in age, primary therapy distribution, prostate-specific antigen levels, Gleason score, clinical T-class at the time of prostate cancer diagnosis, or time lag between the original survey and prostate cancer diagnosis. The standardized incidence ratio (SIR) of prostate cancer was 1.16 [95% confidence interval (CI), 0.62-1.99] and 0.44 (95% CI, 0.29-0.64) among men with and without prostatitis symptoms, respectively. After 15 years of follow-up subsequent to self-reported prostatitis, no evident increase in incidence of prostate cancer was detected among Finnish men with prostatitis symptoms. The higher percentage of prostate cancer among men with prostatitis symptoms appears to be due to coincidentally low SIR of prostate cancer among men without prostatitis symptoms, and may additionally be due to increased diagnostic examinations. Further research is required to confirm this speculation.

  16. In vitro and in silico analysis of the vascular effects of asymmetrical N,N-bis(alkanol)amine aryl esters, novel multidrug resistance-reverting agents. (United States)

    Fusi, F; Durante, M; Spiga, O; Trezza, A; Frosini, M; Floriddia, E; Teodori, E; Dei, S; Saponara, S


    Asymmetrical N,N-bis(alkanol)amine aryl esters (FRA77, GDE6, and GDE19) are potent multidrug resistance (MDR) reversers. Their structures loosely remind that of the Ca(2+) antagonist verapamil. Therefore, the aim of this study was to investigate their vascular activity in vitro. Their effects on the mechanical activity of fresh and cultured rat aorta rings on Cav1.2 channel current (I Ca1.2) of A7r5 cells and their cytotoxicity on A7r5 and EA.hy926 cells were analyzed. Docking at the rat α1C subunit of the Cav1.2 channel was simulated in silico. Compounds tested were cytotoxic at concentrations >1 μM (FRA77, GDE6, GDE19) and >10 μM (verapamil) in EA.hy926 cells, or >10 μM (FRA77, GDE6, GDE19) and at 100 μM (verapamil) in A7r5 cells. In fresh rings, the three compounds partly antagonized phenylephrine and 60 mM K(+) (K60)-induced contraction at concentrations ≥1 and ≥3 μM, respectively. On the contrary, verapamil fully relaxed rings pre-contracted with both agents. In cultured rings, 10 μM GDE6, GDE19, FRA77, and verapamil significantly reduced the contractile response to both phenylephrine and K60. Similarly to verapamil, the three compounds docked at the α1C subunit, interacting with the same amino acids residues. FRA77, GDE6, and GDE19 inhibited I Ca1.2 with IC50 values 1 order of magnitude higher than that of verapamil. FRA77-, GDE6-, and GDE19-induced vascular effects occurred at concentrations that are at least 1 order of magnitude higher than those effectively reverting MDR. Though an unambiguous divergence between MDR reverting and vascular activity is of overwhelming importance, these findings consistently contribute to the design and synthesis of novel and potent chemosensitizers.

  17. Chronic Prostatitis: A Possible Cause of Hematospermia (United States)


    Purpose While hematospermia is mainly caused by genitourinary inflammatory disorders, very few studies have been published on prostatitis-associated hematospermia (PAH) diagnosed using robust prostatitis evaluation methods. Therefore, we have evaluated the incidence of PAH by using systematic methods for evaluating prostatitis. Materials and Methods We evaluated 37 hematospermia patients from a single hospital over the last five years. We classified the patients into PAH versus hematospermia without any evidence of prostatitis (HWP) by using a NIH-Chronic Prostatitis Symptom Index questionnaire and expressed prostatic secretion studies. Results The mean age was 55.89±14.87 years, and the patients were grouped into two groups: one group had 12 HWP patients and the other 25 PAH patients. PAH patients were further sub-classified: chronic bacterial prostatitis (3 patients), chronic nonbacterial prostatitis (10 patients), prostadynia (7 patients), and asymptomatic prostatitis (5 patients). We found Enterococcus faecalis in the three chronic bacterial prostatitis patients. We could not find any statistically significant difference between the PAH and the HWP groups in terms of the age interval, serum prostate-specific antigen level, and prostate volume. Even though there was no statistically significant difference in the items about urination between the two groups, we found a statistically significant difference in the quality of life (QoL) impact for the patients in this study. Conclusions Two-thirds of the hematospermia patients were associated with some evidence of prostatitis. Further, the patients with PAH revealed poor QoL compared with the patients with HWP. Therefore, we must evaluate the presence of prostatitis in hematospermia patients and alleviate the prostatitis-associated symptoms to improve their QoL. PMID:26331127

  18. The Danish Prostate Cancer Database

    Directory of Open Access Journals (Sweden)

    Nguyen-Nielsen M


    Full Text Available Mary Nguyen-Nielsen,1,2 Søren Høyer,3 Søren Friis,4 Steinbjørn Hansen,5 Klaus Brasso,6 Erik Breth Jakobsen,7 Mette Moe,8 Heidi Larsson,9 Mette Søgaard,9 Anne Nakano,9,10 Michael Borre1 1Department of Urology, Aarhus University Hospital, Aarhus, 2Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, 3Department of Pathology, Aarhus University Hospital, Aarhus, 4Danish Cancer Society Research Centre, Danish Cancer Society, Copenhagen, 5Department of Oncology, Odense University Hospital, Odense, 6Copenhagen Prostate Cancer Center and Department of Urology, Rigshospitalet, University of Copenhagen, Copenhagen, 7Department of Urology, Næstved Hospital, Næstved, 8Department of Oncology, Aalborg University Hospital, Aalborg, 9Department of Clinical Epidemiology, Aarhus University Hospital, 10Competence Centre for Health Quality and Informatics (KCKS-Vest, Aarhus, Denmark Aim of database: The Danish Prostate Cancer Database (DAPROCAdata is a nationwide clinical cancer database that has prospectively collected data on patients with incident prostate cancer in Denmark since February 2010. The overall aim of the DAPROCAdata is to improve the quality of prostate cancer care in Denmark by systematically collecting key clinical variables for the purposes of health care monitoring, quality improvement, and research. Study population: All Danish patients with histologically verified prostate cancer are included in the DAPROCAdata. Main variables: The DAPROCAdata registers clinical data and selected characteristics for patients with prostate cancer at diagnosis. Data are collected from the linkage of nationwide health registries and supplemented with online registration of key clinical variables by treating physicians at urological and oncological departments. Main variables include Gleason scores, cancer staging, prostate-specific antigen values, and therapeutic measures (active surveillance, surgery, radiotherapy, endocrine

  19. Clinical value of prostate segmentation and volume determination on MRI in benign prostatic hyperplasia. (United States)

    Garvey, Brian; Türkbey, Barış; Truong, Hong; Bernardo, Marcelino; Periaswamy, Senthil; Choyke, Peter L


    Benign prostatic hyperplasia (BPH) is a nonmalignant pathological enlargement of the prostate, which occurs primarily in the transitional zone. BPH is highly prevalent and is a major cause of lower urinary tract symptoms in aging males, although there is no direct relationship between prostate volume and symptom severity. The progression of BPH can be quantified by measuring the volumes of the whole prostate and its zones, based on image segmentation on magnetic resonance imaging. Prostate volume determination via segmentation is a useful measure for patients undergoing therapy for BPH. However, prostate segmentation is not widely used due to the excessive time required for even experts to manually map the margins of the prostate. Here, we review and compare new methods of prostate volume segmentation using both manual and automated methods, including the ellipsoid formula, manual planimetry, and semiautomated and fully automated segmentation approaches. We highlight the utility of prostate segmentation in the clinical context of assessing BPH.

  20. Prostatic cryptococcosis: a case report

    Directory of Open Access Journals (Sweden)

    M. R. Chang


    Full Text Available Cryptococcosis is a systemic mycosis usually affecting immunodeficient individuals. In contrast, immunologically competent patients are rarely affected. Dissemination of cryptococcosis usually involves the central nervous system, manifesting as meningitis or meningoencephalitis. Prostatic lesions are not commonly found. A case of prostate cryptococcal infection is presented and cases of prostatic cryptococcosis in normal and immunocompromised hosts are reviewed. A fifty-year-old HIV-negative man with urinary retention and renal insufficiency underwent prostatectomy due to massive enlargement of the organ. Prostate histopathologic examination revealed encapsulated yeast-like structures. After 30 days, the patient's clinical manifestations worsened, with headache, neck stiffness, bradypsychia, vomiting and fever. Direct microscopy of the patient's urine with China ink preparations showed capsulated yeasts, and positive culture yielded Cryptococcus neoformans. This fungus was later isolated from cerebrospinal fluid and blood cultures, demonstrating thus its dissemination. The patient was discharged after 27 days in hospital and, despite a regimen of amphotericin B, he died four months later. This case points to cryptococcosis as a possible cause of prostatic disease and reinforces the importance of communication between the medical team and pathology and microbiology laboratories aiming at a more accurate diagnosis and successful treatment.

  1. Lycopene: redress for prostate cancer. (United States)

    Pisipati, Sai Venkata Vedavyas; Pathapati, Harshavardhan; Bhukya, Ganesh; Nuthakki, Suresh; Chandu, Baburao; Nama, SreeKanth; Adeps, RajDev


    Lycopene, a carotenoid is what that gives red colour to some fruits like pomegranate, tomato, papaya etc... People with a sound diet of lycopene may have a less risk of cancers especially prostate cancer which is most impedent for the males of age 40-50 years. So, in countries of north America and Europe food contains much of the lycopene supplements. In accordance with the American journal of epidemiology 2002 studies implies that men with crushed serum lycopene levels are more divulged to prostate cancer and those with sound diet of lycopene have a less risk of prostate cancer. In a care study conveyed by The British journal of urology, men with prostate cancer are subjected to surgery and the tumour is detonated. Amongst the men half a set were supplemented with lycopene supplements and half were not. Those subjected with lycopene supplements have less bone pains and live longer than those not supplemented. This paints a picture about importance of lycopene in treatment of prostate cancer. This article evokes the importance of lycopene and its way of destroying the cancer. Lycopene reduces the risk of cancer by diverging its effect on the plasma Insulin like growth factor, on Connexins , and the most acceptable one, by quench of free radicals.

  2. Prostate cancer and metastasis initiating stem cells

    Institute of Scientific and Technical Information of China (English)

    Kathleen Kelly; Juan Juan Yin


    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.

  3. Giant Benign Prostatic Hyperplasia in a Pakistani Patient

    Directory of Open Access Journals (Sweden)

    Zafaruddin Khan


    Full Text Available “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.

  4. Vaccine Therapy and Pembrolizumab in Treating Patients With Hormone-Resistant, Metastatic Prostate Cancer (United States)


    Hormone-Resistant Prostate Cancer; Metastatic Malignant Neoplasm in the Bone; Metastatic Malignant Neoplasm in the Soft Tissues; Metastatic Prostate Carcinoma; Prostate Adenocarcinoma; Recurrent Prostate Carcinoma; Stage IV Prostate Cancer

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

    Directory of Open Access Journals (Sweden)

    Elkahwaji JE


    Full Text Available 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 initiation and progression. While the pathogenesis of both diseases is not fully understood, benign prostatic hyperplasia and prostate cancer are thought to have a multifactorial etiology, their incidence and prevalence are indeed affected by age and hormones, and they are associated with chronic prostatic inflammation. At least 20% of all human malignancies arise in a tissue microenvironment dominated by chronic or recurrent inflammation. In prostate malignancy, chronic inflammation is an extremely common histopathologic finding; its origin remains a subject of debate and may in fact be multifactorial. Emerging insights suggest that prostate epithelium damage potentially inflicted by multiple environmental factors such as infectious agents, dietary carcinogens, and hormones triggers procarcinogenic inflammatory processes and promotes cell transformation and disease development. Also, the coincidence of chronic inflammation and tumorigenesis in the peripheral zone has recently been linked by studies identifying so-called proliferative inflammatory atrophy as a possible precursor of prostatic intraepithelial neoplasia and prostate cancer. This paper will discuss the available evidence suggesting that chronic inflammation may be involved in the development and progression of chronic prostatic disease, although a direct causal role for chronic inflammation or infection in prostatic carcinogenesis has yet to be established in humans. Further basic and clinical research in the

  6. Mycobacterium abscessus complex bacteremia due to prostatitis after prostate biopsy. (United States)

    Chen, Chung-Hua; Lin, Jesun; Lin, Jen-Shiou; Chen, Yu-Min


    We present the case of a 49-year-old man, who developed Mycobacterium abscessus complex (M. abscessus complex) bacteremia and prostatitis after prostate biopsy. The patient was successfully treated with amikacin with imipenem-cilastatin with clarithromycin. Infections caused by M. abscessus complex have been increasingly described as a complication associated with many invasive procedures. Invasive procedures might have contributed to the occurrence of the M. abscessus complex. Although M. abscessus complex infection is difficult to diagnose and treat, we should pay more attention to this kind of infection, and the correct treatment strategy will be achieved by physicians.

  7. Diagnostic utility of DTI in prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Guerses, Bengi, E-mail: [Yeditepe University Medical Faculty, Department of Radiology, Istanbul (Turkey); Tasdelen, Neslihan [Yeditepe University Medical Faculty, Department of Radiology, Istanbul (Turkey); Yencilek, Faruk [Yeditepe University Medical Faculty, Department of Urology, Istanbul (Turkey); Kilickesmez, N. Ozguer [Yeditepe University Medical Faculty, Department of Radiology, Istanbul (Turkey); Alp, Turgut [Fatih Sultan Mehmet Training and Research Hospital, Division of Urology, Istanbul (Turkey); Firat, Zeynep [Yeditepe University Medical Faculty, Department of Radiology, Istanbul (Turkey); Albayrak, M. Selami [Kartal Training and Research Hospital, Division of Urology, Istanbul (Turkey); Ulug, Aziz M. [Yeditepe University Department of Biomedical Engineering, Istanbul (Turkey); The Feinstein Institute for Medical Research, Manhasset, New York (United States); Guermen, A. Nevzat [Yeditepe University Medical Faculty, Department of Radiology, Istanbul (Turkey)


    Purpose: The aim of this study was to compare the diffusion tensor parameters of prostate cancer, prostatitis and normal prostate tissue. Materials and Methods: A total of 25 patients with the suspicion of prostate cancer were included in the study. MRI was performed with 3 T system (Intera Achieva, Philips Medical Systems, The Netherlands). T2 TSE and DTI with ss-EPI were obtained in each subject. TRUS-guided prostate biopsy was performed after the MRI examination. Images were analyzed by two radiologists using a special software system. ROI's were drawn according to biopsy zones which are apex, midgland, base and central zone on each sides of the gland. FA and ADC values in areas of cancer, chronic prostatitis and normal prostate tissue were compared using Student's t-test. Results: Histopathological analysis revealed carcinoma in 68, chronic prostatitis in 67 and was reported as normal in 65 zones. The mean FA of cancerous tissue was significantly higher (p < 0.01) than the FA of chronic prostatitis and normal gland. The mean ADC of cancerous tissue was found to be significantly lower (p < 0.01), compared with non-cancerous tissue. Conclusion: Decreased ADC and increased FA are compatible with the hypercellular nature of prostate tumors. These differences may increase the accuracy of MRI in the detection of carcinoma and to differentiate between cancer and prostatitis.

  8. Reverting antibiotic tolerance of Pseudomonas aeruginosa PAO1 persister cells by (Z-4-bromo-5-(bromomethylene-3-methylfuran-2(5H-one.

    Directory of Open Access Journals (Sweden)

    Jiachuan Pan

    Full Text Available BACKGROUND: Bacteria are well known to form dormant persister cells that are tolerant to most antibiotics. Such intrinsic tolerance also facilitates the development of multidrug resistance through acquired mechanisms. Thus persister cells are a promising target for developing more effective methods to control chronic infections and help prevent the development of multidrug-resistant bacteria. However, control of persister cells is still an unmet challenge. METHODOLOGY/PRINCIPAL FINDINGS: We show in this report that (Z-4-bromo-5-(bromomethylene-3-methylfuran-2(5H-one (BF8 can restore the antibiotic susceptibility of Pseudomonas aeruginosa PAO1 persister cells at growth non-inhibitory concentrations. Persister control by BF8 was found to be effective against both planktonic and biofilm cells of P. aeruginosa PAO1. Interestingly, although BF8 is an inhibitor of quorum sensing (QS in Gram-negative bacteria, the data in this study suggest that the activities of BF8 to revert antibiotic tolerance of P. aeruginosa PAO1 persister cells is not through QS inhibition and may involve other targets. CONCLUSION: BF8 can sensitize P. aeruginosa persister cells to antibiotics.

  9. Resistance to erucic acid as a selectable marker for peroxisomal activity: isolation of revertants of an infantile Refsum disease cell line. (United States)

    Bachir Bioukar, E; Straehli, F; Ng, K H; Rolland, M O; Hashimoto, T; Carreau, J P; Deschatrette, J


    A system based on the ability of cells to oxidize very long-chain fatty acids (VLCFA) was developed to select in vitro normal human fibroblasts from fibroblasts of patients suffering from peroxisomal disorders with multienzymatic deficiencies: Zellweger syndrome, neonatal adrenoleukodystrophy, infantile Refsum disease (IRD). Cells treated with various concentrations of erucic acid (C22:1 n-9) revealed an enhanced toxicity of this fatty acid for the fibroblasts of patients compared with normal cells. This differential toxicity is correlated with variable accumulations of C22:1 n-9 and the absence of beta-oxidation products in the mutants. Revertants from clonal IRD cell lines were isolated in the selective medium at frequencies ranging from 3 x 10(-7) to 4 x 10(-6) depending on the line. After six weeks of growth in the absence of selective pressure, the variants exhibited a resistance level to C22:1 n-9 identical to that of normal cells. Furthermore, beta-oxidation of VLCFA is re-established in these selected cells as well as dihydroxyacetone phosphate acyltransferase activity. Immunoblot experiments also demonstrated a restored pattern of acyl-CoA oxidase molecular forms. Last, immunofluorescence studies revealed the presence of cytoplasmic structures that were absent in the original IRD cells. Thus, both the deficiencies in metabolic pathways and paucity of the organelle are at least partially corrected in the selected clones.

  10. Proton MR spectroscopy of the prostate

    Energy Technology Data Exchange (ETDEWEB)

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


    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.

  11. [Prostatilen treatment of prostatic adenoma]. (United States)

    Al'-Shukri, S Kh; Gorbachev, A G; Borovets, S Iu; Belousov, V Ia; Kuz'min, I V; Chushkin, K A


    We studied efficacy of repeated courses of prostatilen in suppositories with dimexide in prostatic adenoma patients with normal micturition. Rectal suppositories contain 30 mg prostatilen and 90 mg dimexide. The course consisted of 15 suppositories. The treatment reduced clinical symptoms of infravesical obstruction, residual urine volume in administration of prostatilen in 15-day courses each 3 months. This suggests possibility of suppository prostatilen use not only as an alternative for expensive drugs but also in combination with them in treatment of initial prostatic adenoma.

  12. The Danish Prostate Cancer Database

    DEFF Research Database (Denmark)

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


    . A key feature of DAPROCAdata is the routine collection of patient-reported outcome measures (PROM), including data on quality-of-life (pain levels, physical activity, sexual function, depression, urine and fecal incontinence) and lifestyle factors (smoking, alcohol consumption, and body mass index...... variables include Gleason scores, cancer staging, prostate-specific antigen values, and therapeutic measures (active surveillance, surgery, radiotherapy, endocrine therapy, and chemotherapy). DESCRIPTIVE DATA: In total, 22,332 patients with prostate cancer were registered in DAPROCAdata as of April 2015...

  13. Comparison between prostate volume and intravesical prostatic protrusion in detecting bladder outlet obstruction due to benign prostatic hyperplasia. (United States)

    Hossain, A K M S; Alam, A K M K; Habib, A K M K; Rashid, M M; Rahman, H; Islam, A K M A; Jahan, M U


    The objectives of this study were to determine and compare the correlation of intravesical prostatic protrusion (IPP) and prostate volume (PV) with bladder outlet obstruction (BOO). This study was conducted in the department of urology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh, between July 2009 to September 2010. Fifty benign prostatic hyperplasia (BPH) patients were included in the study. Their evaluation consisted of history along with International Prostate Symptoms Score (IPSS), digital rectal examination (DRE), transabdominal ultrasonography to measure prostate volume, intravesical prostatic protrusion & post voidal residual (PVR) urine and pressure-flow studies to detect bladder outflow obstruction (BOO). Statistical analysis included Unpaired 't' test, Chi-square test and Spearman's Rank correlation test. Receiver Operator Characteristic (ROC) curves were used to compare the correlation of PV and IPP with BOO. Mean prostate volume was significantly larger in bladder outlet obstructed patients (PProstate volume & intravesical prostatic protrusion measured through transabdominal ultrasonography are noninvasive and accessible method that significantly correlates with bladder outlet obstruction in patients with benign prostatic hyperplasia and the correlation of IPP is much more stronger than that of prostate volume.

  14. Prostatitis, sexually transmitted diseases, and prostate cancer: the California Men's Health Study.

    Directory of Open Access Journals (Sweden)

    Iona Cheng

    Full Text Available BACKGROUND: Prostatitis and sexually transmitted diseases (STDs have been positively associated with prostate cancer in previous case-control studies. However, results from recent prospective studies have been inconclusive. METHODOGY/PRINCIPAL FINDINGS: We investigated the association between prostatitis, STDs, and prostate cancer among African American, Asian American, Latino, and White participants of the California Men's Health Study. Our analysis included 68,675 men, who completed a detailed baseline questionnaire in 2002-2003. We identified 1,658 incident prostate cancer cases during the follow-up period to June 30, 2006. Cox proportional hazards models were used to estimate relative risks and 95% confidence intervals. Overall, men having a history of prostatitis had an increased risk of prostate cancer than men with no history (RR = 1.30; 95% CI: 1.10-1.54. Longer duration of prostatitis symptoms was also associated with an increased risk of prostate cancer (P trend = 0.003. In addition, among men screened for prostate cancer (1 or 2 PSA tests, a non-significant positive association was observed between prostatitis and prostate cancer (RR = 1.10; 95% CI: 0.75-1.63. STDs were not associated with overall prostate cancer risk. In racial/ethnic stratified analysis, Latinos reporting any STDs had an increased risk of disease than those with no STDs (RR = 1.43; 95% CI: 1.07-1.91. Interestingly, foreign-born Latinos displayed a larger risk associated with STDs (RR = 1.87; 95% CI: 1.16-3.02 than U.S. born Latinos (RR = 1.15; 95% CI: 0.76-3.02. CONCLUSION: In summary, results from this prospective study suggest that prostatitis and STDs may be involved in prostate cancer susceptibility. While we cannot rule out the possible influence of incidental detection, future studies are warranted to further investigate the role of infectious agents related to prostatitis and STDs in prostate cancer development.

  15. Prostatic and dietary omega-3 fatty acids and prostate cancer progression during active surveillance. (United States)

    Moreel, Xavier; Allaire, Janie; Léger, Caroline; Caron, André; Labonté, Marie-Ève; Lamarche, Benoît; Julien, Pierre; Desmeules, Patrice; Têtu, Bernard; Fradet, Vincent


    The association between omega-3 (ω-3) fatty acids and prostate cancer has been widely studied. However, little is known about the impact of prostate tissue fatty acid content on prostate cancer progression. We hypothesized that compared with the estimated dietary ω-3 fatty acids intake and the ω-3 fatty acids levels measured in red blood cells (RBC), the prostate tissue ω-3 fatty acid content is more strongly related to prostate cancer progression. We present the initial observations from baseline data of a phase II clinical trial conducted in a cohort of 48 untreated men affected with low-risk prostate cancer, managed under active surveillance. These men underwent a first repeat biopsy session within 6 months after the initial diagnosis of low-risk prostate cancer, at which time 29% of the men had progressed from a Gleason score of 6 to a Gleason score of 7. At the first repeat biopsy session, fatty acid levels were assessed with a food-frequency questionnaire, and determined in the RBC and in the prostate tissue biopsy. We found that eicosapentaenoic acid (EPA) was associated with a reduced risk of prostate cancer progression when measured directly in the prostate tissue. Thus, this initial interim study analysis suggests that prostate tissue ω-3 fatty acids, especially EPA, may be protective against prostate cancer progression in men with low-risk prostate cancer.

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

    NARCIS (Netherlands)

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


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

  17. Galiellalactone induces cell cycle arrest and apoptosis through the ATM/ATR pathway in prostate cancer cells. (United States)

    García, Víctor; Lara-Chica, Maribel; Cantarero, Irene; Sterner, Olov; Calzado, Marco A; Muñoz, Eduardo


    Galiellalactone (GL) is a fungal metabolite that presents antitumor activities on prostate cancer in vitro and in vivo. In this study we show that GL induced cell cycle arrest in G2/M phase, caspase-dependent apoptosis and also affected the microtubule organization and migration ability in DU145 cells. GL did not induce double strand DNA break but activated the ATR and ATM-mediated DNA damage response (DDR) inducing CHK1, H2AX phosphorylation (fH2AX) and CDC25C downregulation. Inhibition of the ATM/ATR activation with caffeine reverted GL-induced G2/M cell cycle arrest, apoptosis and DNA damage measured by fH2AX. In contrast, UCN-01, a CHK1 inhibitor, prevented GL-induced cell cycle arrest but enhanced apoptosis in DU145 cells. Furthermore, we found that GL did not increase the levels of intracellular ROS, but the antioxidant N-acetylcysteine (NAC) completely prevented the effects of GL on fH2AX, G2/M cell cycle arrest and apoptosis. In contrast to NAC, other antioxidants such as ambroxol and EGCG did not interfere with the activity of GL on cell cycle. GL significantly suppressed DU145 xenograft growth in vivo and induced the expression of fH2AX in the tumors. These findings identify for the first time that GL activates DDR in prostate cancer.

  18. Sustained Release Oral Nanoformulated Green Tea for Prostate Cancer (United States)


    prostate cancer progression in humans and is being detected in the serum of patients with prostate diseases including prostatitis , benign prostatic ... hypertrophy , and prostate cancer (4). In our study, we found that there was significant inhibition of secreted PSA levels by 13-36%, 26-54% and 57-72% in...TITLE: Sustained Release Oral Nanoformulated Green Tea for Prostate Cancer PRINCIPAL INVESTIGATOR: Hasan Mukhtar, PhD

  19. Stokes polarimetry imaging of dog prostate tissue (United States)

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


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

  20. Prostate cancer vaccines in clinical trials. (United States)

    Lubaroff, David M


    This review presents important information about the current state of the art for vaccine immunotherapy of prostate cancer. It includes important preclinical research for each of the important prostate cancer vaccines to have reached clinical trials. To date, the only prostate cancer vaccine that has completed Phase III trials and has been approved and licensed by the US FDA is Sipuleucel-T, which immunizes patients against the prostate-associated antigen prostatic acid phosphatase. The benefits and concerns associated with the vaccine are presented. A current Phase III trial is currently underway using the vaccinia-based prostate-specific antigen vaccine Prostvac-TRICOM. Other immunotherapeutic vaccines in trials include the Ad/prostate-specific antigen vaccine Ad5-prostate-specific antigen and the DNA/prostatic acid phosphatase vaccine. A cellular vaccine, GVAX, has been in clinical trials but has not seen continuous study. This review also delves into the multiple immune regulatory elements that must be overcome in order to obtain strong antitumor-associated antigen immune responses capable of effectively destroying prostate tumor cells.

  1. Reasons for the weak correlation between prostate volume and urethral resistance parameters in patients with prostatism

    NARCIS (Netherlands)

    R. Kranse (Ries); R. van Mastrigt (Ron); F.H. Schröder (Fritz); J.L.H.R. Bosch (Ruud)


    textabstractIn an attempt to increase our understanding of the clinical syndrome of benign prostatic hyperplasia (BPH) an analysis was made of the association between prostate volume as measured by transrectal ultrasound and several reported urodynamically determined urethral resis

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

    LENUS (Irish Health Repository)

    Duffy, Michael J


    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.

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

    Sarwar, Shahana; Adil, Mohammed Abdul Majid; Nyamath, Parveen; Ishaq, Mohammed


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

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

    Sarwar, Shahana; Nyamath, Parveen; Ishaq, Mohammed


    Prostatitis, BPH, and P.Ca are the most frequent pathologies of the prostate gland that are responsible for morbidity in men. Raised levels of PSA are seen in different pathological conditions involving the prostate. PAP levels are altered in inflammatory or infectious or abnormal growth of the prostate tissue. Serum calcium and phosphorus levels were also found to be altered in prostate cancer and BPH. The present study was carried out to study the levels of PSA, PAP, calcium, and phosphorus in serum of patients with Prostatitis, BPH, or P.Ca and also to evaluate the relationship between them. Males in the age group of 50–85 years with LUTS disease symptoms and with PSA levels more than 4 ng/mL were included. A total of 114 patients were analyzed including 30 controls. Prostatitis in 35.7% of cases, BPH in 35.7% of the cases, and P.Ca in 28.57% of the cases were observed. Thus, the nonmalignant cases constitute a majority. PSA, a marker specific for prostatic conditions, was significantly high in all the diseases compared to controls. A rise in serum PSA and PAP indicates prostatitis or, in combination with these two tests, decreased serum calcium shows advanced disease. PMID:28168057

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

    Directory of Open Access Journals (Sweden)

    Shahana Sarwar


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

  6. [Chronic prostatitis and Bechterew's disease]. (United States)

    Kohlicek, J; Svec, V


    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.

  7. Prostate Cancer Research Training Program (United States)


    evaluate medication safety. Examples of HERCe research include recent publications on breast cancer treatments, complications of chemotherapy for...with specific interest in minimally invasive procedures, new techniques, and outcomes. Dr. Brown initiated many of the laparoscopic and robotic ... surgery as it is one of the main areas of his clinical expertise. Currently, he performs more prostate cancer surgery than any other physician in

  8. Sarcomatoid carcinoma of the prostate. (United States)

    Açıkgöz, Onur; Gazel, Eymen; Zengin, Neslihan İnci; Kasap, Yusuf; Camtosun, Ahmet; Yazıcıoğlu, Ahmet Hamdi


    Sarcomatoid carcinoma of the prostate is among the rarest malignant neoplasm types and has been well known for its aggressive clinical course. Patient was admitted with the symptoms of lower urinary tract. Transurethral resection of prostate (TUR-P) was carried out. Revealing Gleason 5 + 3 = 8 prostate adenocarcinoma in TUR-P material. Thereby, a Radical Prostatectomy procedure was planned. In operation, frozen examination revealed adenocarcinoma metastasis to the obturator lymph node. The operation was terminated. In the postoperative 3rd month, the patient was re-admitted with acute urinary system symptoms. A cystoscopy performed and complete resection of the mass was performed. The pathological examination reported that the tumor was compatible with undifferentiated adenocarcinoma owing to presence of poorly differentiated tumoral cells and detection of adenocarcinoma in a relatively small (<1%) focus. 4 month after the operation, the patient underwent another cyctoscopic examination which revealed the prostatic lounge and most of the bladder lumen to be filled with tumoral tissue. The tumoral tissues was resected incompletely. This material was diagnosed to be "Sarcomatoid Malignant Tumor" upon the new evidences of progressive dedifferentiation and predominant sarcomatoid appearance, compared with the former TUR-P materials. Subsequent PET-CT scan depicted multiple metastasis. The patient was referred to oncology department. In conclusion, sarcomatoid carcinoma is a malignant variant that brings along diagnostic and treatment difficulties.

  9. Sarcomatoid Carcinoma of the Prostate

    Directory of Open Access Journals (Sweden)

    Onur Açıkgöz


    Full Text Available Sarcomatoid carcinoma of the prostate is among the rarest malignant neoplasm types and has been well known for its aggressive clinical course. Patient was admitted with the symptoms of lower urinary tract. Transurethral resection of prostate (TUR-P was carried out. Revealing Gleason 5 + 3 = 8 prostate adenocarcinoma in TUR-P material. Thereby, a Radical Prostatectomy procedure was planned. In operation, frozen examination revealed adenocarcinoma metastasis to the obturator lymph node. The operation was terminated. In the postoperative 3rd month, the patient was re-admitted with acute urinary system symptoms. A cystoscopy performed and complete resection of the mass was performed. The pathological examination reported that the tumor was compatible with undifferentiated adenocarcinoma owing to presence of poorly differentiated tumoral cells and detection of adenocarcinoma in a relatively small (1% focus. 4 month after the operation, the patient underwent another cyctoscopic examination which revealed the prostatic lounge and most of the bladder lumen to be filled with tumoral tissue. The tumoral tissues was resected incompletely. This material was diagnosed to be “Sarcomatoid Malignant Tumor” upon the new evidences of progressive dedifferentiation and predominant sarcomatoid appearance, compared with the former TUR-P materials. Subsequent PET-CT scan depicted multiple metastasis. The patient was referred to oncology department. In conclusion, sarcomatoid carcinoma is a malignant variant that brings along diagnostic and treatment difficulties.

  10. Nebraska Prostate Cancer Research Program (United States)


    2011.  LaTayia Aaron and Joann Powell. (2012). Dioxin exposure enhances nuclear localization of androgen be trained in different areas of prostate cancer research. For example, the focus areas or research include Biomarkers , Therapy, Genetics, and...example, the focus areas or research include Biomarkers , Therapy, Genetics, and Tumor Biology as outlined by the laboratory research descriptions in the

  11. Prostate Cancer Risk Prediction Models (United States)

    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.


    Institute of Scientific and Technical Information of China (English)


    @@ 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.

  13. Prostate Cancer, Prostate Cancer Death, and Death from Other Causes, Among Men with Metabolic Aberrations


    Häggström, Christel; Stocks, Tanja; Nagel, Gabriele; Manjer, Jonas; Bjørge, Tone; Hallmans, Göran; Engeland, Anders; Ulmer, Hanno; Lindkvist, Bjorn; Selmer, Randi; Concin, Hans; Tretli, Steinar; Jonsson, Håkan; Stattin, Pär


    Background: Few previous studies of metabolic aberrations and prostate cancer risk have taken into account the fact that men with metabolic aberrations have an increased risk of death from causes other than prostate cancer. The aim of this study was to calculate, in a real-life scenario, the risk of prostate cancer diagnosis, prostate cancer death, and death from other causes. Methods: In the Metabolic Syndrome and Cancer Project, prospective data on body mass index, blood pressure, glucose, ...

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

    DEFF Research Database (Denmark)

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


    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....

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

    Directory of Open Access Journals (Sweden)

    Ivona Pandrea


    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.

  16. Enhancing NAD+ Salvage Pathway Reverts the Toxicity of Primary Astrocytes Expressing Amyotrophic Lateral Sclerosis-linked Mutant Superoxide Dismutase 1 (SOD1). (United States)

    Harlan, Benjamin A; Pehar, Mariana; Sharma, Deep R; Beeson, Gyda; Beeson, Craig C; Vargas, Marcelo R


    Nicotinamide adenine dinucleotide (NAD(+)) participates in redox reactions and NAD(+)-dependent signaling pathways. Although the redox reactions are critical for efficient mitochondrial metabolism, they are not accompanied by any net consumption of the nucleotide. On the contrary, NAD(+)-dependent signaling processes lead to its degradation. Three distinct families of enzymes consume NAD(+) as substrate: poly(ADP-ribose) polymerases, ADP-ribosyl cyclases (CD38 and CD157), and sirtuins (SIRT1-7). Because all of the above enzymes generate nicotinamide as a byproduct, mammalian cells have evolved an NAD(+) salvage pathway capable of resynthesizing NAD(+) from nicotinamide. Overexpression of the rate-limiting enzyme in this pathway, nicotinamide phosphoribosyltransferase, increases total and mitochondrial NAD(+) levels in astrocytes. Moreover, targeting nicotinamide phosphoribosyltransferase to the mitochondria also enhances NAD(+) salvage pathway in astrocytes. Supplementation with the NAD(+) precursors nicotinamide mononucleotide and nicotinamide riboside also increases NAD(+) levels in astrocytes. Amyotrophic lateral sclerosis (ALS) is caused by the progressive degeneration of motor neurons in the spinal cord, brain stem, and motor cortex. Superoxide dismutase 1 (SOD1) mutations account for up to 20% of familial ALS and 1-2% of apparently sporadic ALS cases. Primary astrocytes isolated from mutant human superoxide dismutase 1-overexpressing mice as well as human post-mortem ALS spinal cord-derived astrocytes induce motor neuron death in co-culture. Increasing total and mitochondrial NAD(+) content in ALS astrocytes increases oxidative stress resistance and reverts their toxicity toward co-cultured motor neurons. Taken together, our results suggest that enhancing the NAD(+) salvage pathway in astrocytes could be a potential therapeutic target to prevent astrocyte-mediated motor neuron death in ALS.

  17. Gene therapy for prostate cancer.

    LENUS (Irish Health Repository)

    Tangney, Mark


    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

  18. Association between prostatic resistive index and cardiovascular risk factors in patients with benign prostatic hyperplasia. (United States)

    Baykam, Mehmet Murat; Aktas, Binhan Kagan; Bulut, Suleyman; Ozden, Cuneyt; Deren, Tagmac; Tagci, Suleyman; Gokkaya, Cevdet Serkan; Memis, Ali


    We evaluated the relationship between prostatic resistive index (RI) and cardiovascular system (CVS) risk factors in patients with benign prostatic hyperplasia. The study included 120 patients who were attending our outpatient clinic with lower urinary tract symptoms related to benign prostatic hyperplasia. The clinical, laboratory, anthropometric data, and CVS risk factors (hypertension, diabetes mellitus, metabolic syndrome, history of CVS events, and smoking) of the patients were evaluated regarding the association between prostate RI level by regression analyses. The prostatic RI levels of the patients were measured using power Doppler imaging. In univariate regression analysis, there were statistically significant relationships between prostatic RI levels and the patients' age, International Prostate Symptom Score, hip circumference, fasting blood glucose, prostate specific antigen, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total prostate volume, uroflowmetric maximal flow rate, and all investigated CVS risk factors (p prostatic RI levels were found to be associated with fasting blood glucose and total prostate volume, and also with CVS risk factors including only metabolic syndrome and cigarette smoking in the multivariate regression analysis. Our results showed that prostatic RI level is significantly related to metabolic syndrome and smoking among the investigated CVS risk factors.

  19. [Bacterial prostatitis and prostatic fibrosis: modern view on the treatment and prophylaxis]. (United States)

    Zaitsev, A V; Pushkar, D Yu; Khodyreva, L A; Dudareva, A A


    Treatments of chronic bacterial prostatitis (CP) remain difficult problem. Bacterial prostatitis is a disease entity diagnosed clinically and by evidence of inflammation and infection localized to the prostate. Risk factors for UTI in men include urological interventions, such as transrectal prostate biopsy. Ensuing infections after prostate biopsy, such as UTI and bacterial prostatitis, are increasing due to increasing rates of fluoroquinolone resistance. The increasing global antibiotic resistance also significantly affects management of UTI in men, and therefore calls for alternative strategies. Prostatic inflammation has been suggested to contribute to the etiology of lower urinary tract symptoms (LUTS) by inducing fibrosis. Several studies have shown that prostatic fibrosis is strongly associated with impaired urethral function and LUTS severity. Fibrosis resulting from excessive deposition of collagen is traditionally recognized as a progressive irreversible condition and an end stage of inflammatory diseases; however, there is compelling evidence in both animal and human studies to support that the development of fibrosis could potentially be a reversible process. Prostate inflammation may induce fibrotic changes in periurethral prostatic tissues, promote urethral stiffness and LUTS. Patients experiencing CP and prostate-related LUTS could benefit from anti-inflammatory therapies, especially used in combination with the currently prescribed enzyme treatment with Longidase. Treatment results showed that longidase is highly effective in bacterial and abacterial CP. Longidase addition to standard therapeutic methods significantly reduced the disease symptoms and regression of inflammatory-proliferative alterations in the prostate.


    Directory of Open Access Journals (Sweden)

    A. S. Pere


    Full Text Available The review of current insights into the role of the previous inflammation in the prostate gland and the development of prostate cancer are presented. The consecutive changes of cellular structures are characterized by proliferative inflammatory atrophy and prostatic intraepithelial neoplasia.


    Directory of Open Access Journals (Sweden)

    A. S. Pere


    Full Text Available The review of current insights into the role of the previous inflammation in the prostate gland and the development of prostate cancer are presented. The consecutive changes of cellular structures are characterized by proliferative inflammatory atrophy and prostatic intraepithelial neoplasia.

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

    NARCIS (Netherlands)

    P.J. van Leeuwen (Pim)


    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

  3. Prospective, Randomized, Multinational Study of Prostatic Urethral Lift Versus Transurethral Resection of the Prostate

    DEFF Research Database (Denmark)

    Sønksen, Jens; Barber, Neil J; Speakman, Mark J


    BACKGROUND: Transurethral resection of the prostate (TURP) is considered the gold standard for male lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). However, TURP may lead to sexual dysfunction and incontinence, and has a long recovery period. Prostatic urethral...

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

    NARCIS (Netherlands)

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


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


    NARCIS (Netherlands)



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

  6. Ectopic mineral formation in the prostate gland

    Directory of Open Access Journals (Sweden)



    Full Text Available This work analyzes the data of cont emporary scientific literature regarding the ectopic mineralization in the prostate gland, its pathogenetic features are considered. The scientific literature of recent decades gives grounds to assert that the processes of concrement formation in the prostate gland are influenced by many factors, pathological mineralization can be realized by different mechanisms. They include chronic inflammation, stagnation fract ions in gland, reflux of urine from the urethra at intravesicle obstruction, malformation of prostate and seminal vesicles, specific inflammation, polymorphism of gene protein inhibitors of calcification. These mechanisms are interconnected, each of them may participate in the overall development of concrement fo rmation in the prostate. In recent years, due to improved instrumental diagnosis we observe a significant increase of the number of patients, who were found with pathogenic prostate gland biol iths, which requires more detailed and in-depth study of the mechanisms of mineral formation in the prostate.

  7. Psychosocial Consequences of Overdiagnostic of Prostate Cancer

    DEFF Research Database (Denmark)

    Nielsen, Sigrid Brisson; Brodersen, John

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

  8. Testosterone replacement therapy and prostate health. (United States)

    Polackwich, A Scott; Ostrowski, Kevin A; Hedges, Jason C


    There is an emerging evolution in the understanding of the relationship between the prostate and testosterone. It has long been generally believed that with testosterone replacement therapy (TRT), increasing serum testosterone levels led to prostatic growth and worsening of voiding dysfunction and associated complications. A new theory, the Saturation Model of Testosterone and its effect on the Prostate has gained attention. This theory suggests that the prostate's response to increasing levels of serum testosterone reaches a limit beyond which there is minimal effect. This model predicts that testosterone replacement therapy occurs above this saturation point, and replacing testosterone to eugonadal levels should not worsen prostate related benign disease. We evaluated the recent published data, with an emphasis on clinical studies done within the last 3 years, for the effects of testosterone supplementation on benign prostatic disease.

  9. Mitochondria, prostate cancer, and biopsy sampling error. (United States)

    Parr, Ryan L; Mills, John; Harbottle, Andrew; Creed, Jennifer M; Crewdson, Gregory; Reguly, Brian; Guimont, François S


    Mitochondria and their associated genome are emerging as sophisticated indicators of prostate cancer biology. Alterations in the mitochondrial genome (mtgenome) have been implicated in cell proliferation, metastatic behavior, androgen independence, as a signal for apoptosis, and as a predictor of biochemical recurrence. Somatic mutation patterns in complete mtgenomes are associated with prostate specific antigen levels (PSA) in prostate cancer patients and a large-scale mtgenome deletion (3.4 kb) is consistent with a prostate "cancerization" field effect. This review will focus on the biological characteristics of mitochondria and their direct clinical application to prostate cancer. Mitochondrial science is currently influencing clinical prostate cancer diagnostics and the rapid progress in this area indicates future, break-through contributions in the general field of oncology.

  10. Dystrophic Calcification of the Prostate after Cryotherapy (United States)


    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. PMID:25548712

  11. Caveolin-1 and prostate cancer progression. (United States)

    Freeman, Michael R; Yang, Wei; Di Vizio, Dolores


    Caveolin-1 was identified in the 1990s as a marker of aggressive prostate cancer. The caveolin-1 protein localizes to vesicular structures called caveolae and has been shown to bind and regulate many signaling proteins involved in oncogenesis. Caveolin-1 also has lipid binding properties and mediates aspects of cholesterol and fatty acid metabolism and can elicit biological responses in a paracrine manner when secreted. Caveolin-1 is also present in the serum of prostate cancer patients and circulating levels correlate with extent of disease. Current evidence indicates that increased expression of caveolin-1 in prostate adenocarcinoma cells and commensurate downregulation of the protein in prostate stroma, mediate progression to the castration-resistant phase of prostate cancer through diverse pathways. This chapter summarizes the current state of our understanding of the cellular and physiologic mechanisms in which caveolin-1 participates in the evolution of prostate cancer cell phenotypes.

  12. Development of New Treatments for Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

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


    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

  13. Dystrophic Calcification of the Prostate after Cryotherapy

    Directory of Open Access Journals (Sweden)

    Christopher Dru


    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.

  14. The genomic landscape of prostate cancer

    Directory of Open Access Journals (Sweden)

    Sylvan eBaca


    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.

  15. Prostate Cancer Genomics: Toward a New Understanding


    John S Witte


    Recent genetics and genomics studies of prostate cancer help clarify the genetic basis of this common but complex disease. Genome-wide studies have detected numerous variants associated with disease as well as common gene fusions and expression ‘signatures’ in prostate tumors. Based on these results, some advocate gene-based individualized screening for prostate cancer, although such testing may only be worthwhile to distinguish disease aggressiveness. Lessons learned here provide strategies ...

  16. Prostate Cancer Presenting with Parietal Bone Metastasis (United States)

    Pare, Abdoul Karim; Abubakar, Babagana Mustapha; Kabore, Moussa


    Bone metastases from prostate cancer are very common. They are usually located on the axial skeleton. However, cranial bone metastases especially to the parietal bone are rare. We report a case of metastatic prostate cancer presenting with left parietal bone metastasis in a patient with no urological symptoms or signs. We should consider prostate cancer in any man above 60 years presenting unusual bone lesions.

  17. Targeting Discoidin Domain Receptors in Prostate Cancer (United States)


    1 AWARD NUMBER: W81XWH-15-1-0226 TITLE: Targeting Discoidin Domain Receptors in Prostate Cancer PRINCIPAL INVESTIGATOR: Dr. Rafael Fridman...4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-15-1-0226 Targeting Discoidin Domain Receptors in Prostate Cancer 5b. GRANT NUMBER W81XWH-15...DDRs in prostate cancer . During the first funding period, we conducted immunohistochemical studies by staining a 200 case Grade/Stage tissue

  18. Primary and salvage cryotherapy for prostate cancer. (United States)

    Finley, David S; Pouliot, Frederic; Miller, David C; Belldegrun, Arie S


    Cryotherapy is a technique to ablate tissue by local induction of extremely cold temperatures. Recently, the American Urological Association Best Practice Statement recognized cryoablation of the prostate as an established treatment option for men with newly diagnosed or radiorecurrent organ-confined prostate cancer. Emerging data suggest that, in select cases, cryoablation may have a role in focal ablation of prostate. The current state of the art of cryoablation in these applications is reviewed.

  19. Endocrine Disruption and Human Prostate Cancer (United States)


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

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


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

  1. Diagnostic accuracy of urinary prostate protein glycosylation profiling in prostatitis diagnosis (United States)

    Vermassen, Tijl; Van Praet, Charles; Poelaert, Filip; Lumen, Nicolaas; Decaestecker, Karel; Hoebeke, Piet; Van Belle, Simon; Rottey, Sylvie


    Introduction Although prostatitis is a common male urinary tract infection, clinical diagnosis of prostatitis is difficult. The developmental mechanism of prostatitis is not yet unraveled which led to the elaboration of various biomarkers. As changes in asparagine-linked-(N-)-glycosylation were observed between healthy volunteers (HV), patients with benign prostate hyperplasia and prostate cancer patients, a difference could exist in biochemical parameters and urinary N-glycosylation between HV and prostatitis patients. We therefore investigated if prostatic protein glycosylation could improve the diagnosis of prostatitis. Materials and methods Differences in serum and urine biochemical markers and in total urine N-glycosylation profile of prostatic proteins were determined between HV (N = 66) and prostatitis patients (N = 36). Additionally, diagnostic accuracy of significant biochemical markers and changes in N-glycosylation was assessed. Results Urinary white blood cell (WBC) count enabled discrimination of HV from prostatitis patients (P < 0.001). Urinary bacteria count allowed for discriminating prostatitis patients from HV (P < 0.001). Total amount of biantennary structures (urinary 2A/MA marker) was significantly lower in prostatitis patients compared to HV (P < 0.001). Combining the urinary 2A/MA marker and urinary WBC count resulted in an AUC of 0.79, 95% confidence interval (CI) = (0.70–0.89) which was significantly better than urinary WBC count (AUC = 0.70, 95% CI = [0.59–0.82], P = 0.042) as isolated test. Conclusions We have demonstrated the diagnostic value of urinary N-glycosylation profiling, which shows great potential as biomarker for prostatitis. Further research is required to unravel the developmental course of prostatic inflammation. PMID:26526330

  2. Smoking and prostate cancer survival and recurrence

    Institute of Scientific and Technical Information of China (English)

    Roberto L Muller; Daniel M Moreira


    Smooking is associated with several major benign and malignant diseases,representing one of the most important modifiable risk factors.Among urothelial neoplasms,smoking is pivotal in tumor carcinogenesis,but its role in prostate cancer is still controversial.Many authors have failed to demonstrate an association between smoking and prostate cancer.1-3 However,large epidemiological studies have shown that smoking is associated with higher risk of developing and dying of prostate cancer.4 Thus,large sample sizes and long follow-ups are important when studying prostate cancer given that its natural history can be quite long.

  3. Effects of verbenalin on prostatitis mouse model (United States)

    Miao, Mingsan; Guo, Lin; Yan, Xiaoli; Wang, Tan; Li, Zuming


    The aim of this study was to observe the treatment characteristics of verbenalin on a prostatitis mouse model. Give Xiaozhiling injection in the prostate locally to make a prostatitis mouse model. High, medium and low doses of verbenalin were each given to different mouse groups. The amount of water was determined in 14th, 28th. The number of white cells and lecithin corpuscle density in prostatic fluid were determined. Morphological changes in the prostate, testis, epididymis and kidney were detected. Compared with the model control group, the mice treated with high, medium and low doses of verbenalin had significantly increased amounts of water, and prostate white blood cell count and prostate volume density (Vv) were decreased significantly, the density of lecithin corpuscle score increased, and pathologic prostatitis changes were significantly reduced. Pathological change in the testis was significantly reduced and the change in the epididymis was obviously reduced. The thymic cortex thickness and the number of lymphocytes increased significantly and could reduce the renal pathological changes in potential. Verbenalin has a good therapeutic effect on the prostatitis mouse model. PMID:26858560

  4. Role of androgen receptor in prostate cancer

    Institute of Scientific and Technical Information of China (English)

    HiroyoshiSuzuki; HaruoIto


    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.

  5. Overview of Dietary Supplements in Prostate Cancer. (United States)

    Yacoubian, Aline; Dargham, Rana Abu; Khauli, Raja B; Bachir, Bassel G


    Prostate cancer is a key health concern for men with its etiology still under investigation. Recently, the role of dietary supplements has been noted to have a major inhibitory effect on prostate cancer and numerous studies have been conducted in this regard. This review provides a summary on numerous recent studies conducted in this field. Some of the studies reviewed revealed a protective role for supplements, and others showed no correlation while some even had an adverse effect. The mechanism of how these supplements act on the prostate is still not clear. Further studies are warranted especially for supplements that have been shown to have a potential inhibitory role in prostate cancer.

  6. Generalized Lymphadenopathy: Unusual Presentation of Prostate Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Bulent Cetin


    Full Text Available Generalized lymphadenopathy is a rare manifestation of metastatic prostate cancer. Here, we report the case of a 59-year-old male patient with supraclavicular, mediastinal, hilar, and retroperitoneal and inguinal lymphadenopathy, which suggested the diagnosis of lymphoma. There were no urinary symptoms. A biopsy of the inguinal lymph node was compatible with adenocarcinoma, whose prostatic origin was shown by immunohistochemical staining with PSA. The origin of the primary tumor was confirmed by directed prostate biopsy. We emphasize that a suspicion of prostate cancer in men with adenocarcinoma of undetermined origin is important for an adequate diagnostic and therapeutic approach.

  7. Immunotherapy and Immune Evasion in Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Thakur, Archana, E-mail:; Vaishampayan, Ulka [Department of Oncology, Wayne State University, Detroit, MI 48201 (United States); Lum, Lawrence G., E-mail: [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)


    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.

  8. Spindle-cell carcinoma of the prostate

    Directory of Open Access Journals (Sweden)

    Carlos Hirokatsu Watanabe Silva


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

  9. Emphysematous prostatic abscess with rectoprostatic fistula

    Directory of Open Access Journals (Sweden)

    Po-Cheng Chen


    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.

  10. Liver protects metastatic prostate cancer from induced death by activating E-cadherin signaling. (United States)

    Ma, Bo; Wheeler, Sarah E; Clark, Amanda M; Whaley, Diana L; Yang, Min; Wells, Alan


    Liver is one of the most common sites of cancer metastasis. Once disseminated, the prognosis is poor as these tumors often display generalized chemoresistance, particularly for carcinomas that derive not from the aerodigestive tract. When these cancers seed the liver, the aggressive cells usually undergo a mesenchymal to epithelial reverting transition that both aids colonization and renders the tumor cells chemoresistant. In vitro studies demonstrate that hepatocytes drive this phenotypic shift. However, the in vivo evidence and the molecular signals that protect these cells from induced death are yet to be defined. Herein, we report that membrane surface E-cadherin-expressing prostate cancer cells were resistant to cell death by chemotherapeutic drugs but E-cadherin null cells or those expressing E-cadherin only in the cytoplasm were sensitive to death signals and chemotherapies both in vitro and in vivo. While cell-cell E-cadherin ligandation reduced mitogenesis, this chemoprotection was proliferation-independent as killing of both 5-ethynyl-2'-deoxyuridine-positive (or Ki67(+) ) and 5-ethynyl-2'-deoxyuridine-negative (Ki67(-) ) cells was inversely related to membrane-bound E-cadherin. Inhibiting the canonical survival kinases extracellular signal-regulated protein kinases, protein kinase B, and Janus kinase, which are activated by chemotherapeutics in epithelial cell-transitioned prostate cancer, abrogated the chemoresistance both in cell culture and in animal models of metastatic cancer. For disseminated tumors, protein kinase B disruption in itself had no effect on tumor survival but was synergistic with chemotherapy, leading to increased killing.

  11. Endotoxins in the prostatic secretions of chronic prostatitis patients

    Institute of Scientific and Technical Information of China (English)

    Yu-Ping Dai; Xiang-Zhou Sun; Ke-Li Zheng


    Aim: To evaluate the clinical significance of the quantitative determinations of endotoxins in the expressed prostatic secretions (EPS) of chronic prostatitis (CP) patients. Methods: The EPS of 45 patients with CP and 15 normal volunteers were obtained for microscopic examination, bacterial culture and endotoxin determination. The level of endotoxins was determined by the Limulus-amebocyte-lysate test with chromogenic substrate. Results: Patients (P>0.05), type Ⅱ/type Ⅲa vs. Normal controls P < 0.05)]. Conclusion: CP patients have elevated levels of endotoxins in the EPS, which suggests that inflammation is a feature of this disease. EPS endotoxin determination is not only helpful in diagnostic confirmation, but also in evaluating the response to treatment in CP patients.

  12. A Rare Prostatic Diagnosis of an Old Man: A Pure Prostatic Leiomyoma

    Directory of Open Access Journals (Sweden)

    W. M. van Ulden-Bleumink


    Full Text Available A pure leiomyoma of the prostate is a rare benign tumor. An 82-year-old man was referred to our urology department with gross hematuria and complete urinary retention. Examination revealed a benign prostatic hyperplasia. Transrectal ultrasound showed a prostate of 125 mL. Serum PSA was 1.9 µg/L. A simple retropubic prostatectomy was performed. Histopathological examination showed a pure leiomyoma of the prostate, without the presence of glandular prostate tissue. The diagnosis, characteristics, and treatment of this tumor are described.

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

    Energy Technology Data Exchange (ETDEWEB)

    Mok, Gary [Department of Radiation Oncology, Geneva University Hospital, Geneva (Switzerland); Department of Radiation Oncology, Centre Intégré de Cancérologie de Laval, Centre de Santé et de Services Sociaux de Laval, Laval, Québec (Canada); Department of Radiology, Radiation Oncology, and Nuclear Medicine, Centre Hospitalier Universitaire de Montréal, Montréal, Québec (Canada); Benz, Eileen [Department of Radiation Oncology, Geneva University Hospital, Geneva (Switzerland); Vallee, Jean-Paul [Department of Radiology, Geneva University Hospital, Geneva (Switzerland); Miralbell, Raymond [Department of Radiation Oncology, Geneva University Hospital, Geneva (Switzerland); Zilli, Thomas, E-mail: [Department of Radiation Oncology, Geneva University Hospital, Geneva (Switzerland)


    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.

  14. Prostate Cancer: Symptoms, Diagnosis and Treatment | NIH MedlinePlus the Magazine (United States)

    ... turn Javascript on. Feature: Prostate Cancer Prostate Cancer: Symptoms, Diagnosis and Treatment Past Issues / Winter 2010 Table of Contents Symptoms Prostate cancer has no symptoms in its early ...

  15. Prostatic intraepithelial neoplasia-like ductal prostatic adenocarcinoma: A case suitable for active surveillance?

    Directory of Open Access Journals (Sweden)

    Soroush Rais-Bahrami


    Full Text Available In contrast to typical prostatic ductal adenocarcinoma, prostatic intraepithelial neoplasia (PIN-like ductal adenocarcinoma is a rare variant of prostate cancer with low-grade clinical behavior. We report a case of a 66-year-old African-American male with an elevated serum prostate-specific antigen who underwent multiparametric prostate magnetic resonance imaging (MRI and MRI/ultrasound fusion-guided biopsies. Pathology demonstrated low-volume Gleason score 3 + 3 = 6 (Grade Group 1, acinar adenocarcinoma involving one core and PIN-like ductal adenocarcinoma on a separate core. Herein, we discuss the potential role of active surveillance for patients with this rare variant of prostate cancer found in the era of advanced imaging with multiparametric MRI for prostate cancer.

  16. Radiologic presentation of chronic granulomatous prostatitis mimicking locally advanced prostate adenocarcinoma. (United States)

    Lee, Su-Min; Joshi, Jay; Wolfe, Konrad; Acher, Peter; Liyanage, Sidath H


    We present a case of nonspecific granulomatous prostatitis (GP), a clinical mimic of prostate adenocarcinoma. A 54-year-old man presented with lower urinary tract symptoms and raised prostate-specific antigen. Magnetic resonance imaging showed features consistent with prostate cancer, including low T2-signal intensity in the peripheral and transition zones with signs of extracapsular extension. Diffusion-weighted imaging showed high-signal intensity, with low apparent diffusion coefficient values, whereas dynamic contrast enhancement demonstrated a type 3 washout curve, similar to that found in prostate cancer. Transperineal sector-guided prostate biopsy confirmed nonspecific GP, and the patient was treated conservatively. We discuss and compare nonspecific, chronic GP as a radiologic mimic of prostate adenocarcinoma patient.

  17. Radiologic presentation of chronic granulomatous prostatitis mimicking locally advanced prostate adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Su-Min Lee


    Full Text Available We present a case of nonspecific granulomatous prostatitis (GP, a clinical mimic of prostate adenocarcinoma. A 54-year-old man presented with lower urinary tract symptoms and raised prostate-specific antigen. Magnetic resonance imaging showed features consistent with prostate cancer, including low T2-signal intensity in the peripheral and transition zones with signs of extracapsular extension. Diffusion-weighted imaging showed high-signal intensity, with low apparent diffusion coefficient values, whereas dynamic contrast enhancement demonstrated a type 3 washout curve, similar to that found in prostate cancer. Transperineal sector-guided prostate biopsy confirmed nonspecific GP, and the patient was treated conservatively. We discuss and compare nonspecific, chronic GP as a radiologic mimic of prostate adenocarcinoma patient.

  18. The results of transrectal prostate biopsy in patients with low levels of prostate specific antigen

    Directory of Open Access Journals (Sweden)

    Ahmet Ali Sancaktutar


    Full Text Available Objectives: The aim of this study is to evaluate the resultsof prostate biopsy of patients who had the prostatespecificantigen (PSA levels below 4 ng/ml.Material and methods: The medical records of 63 patientswho underwent transrectal prostate biopsy, betweenJanuary 2005 and December 2011, due to suspicionof prostate cancer with the PSA levels under 4 ng/mlwere retrospectively reviewed.Results: Transrectal Prostate biopsy was performed to63 patients. Prostate cancer was detected in 12 (19%patients. The mean value of PSA was 2.5 ng/ml. TheGleason score of Prostate cancer patients was 6,8 (5-7and the number of positive cores were 3.Conclusions: The rate of prostate cancer was found as19% in patients with levels of PSA under 4 ng/ml and thisratio is compatible with the results of previous reports.

  19. Expression of cyclooxygenase-2 in prostate adenocarcinoma and benign prostatic hyperplasia. (United States)

    Lee, L M; Pan, C C; Cheng, C J; Chi, C W; Liu, T Y


    Elevated expression of cyclo-oxygenase (COX)-2 has been found in several human cancers, including prostate adenocarcinoma. To evaluate the potential prognostic role of COX-2 in prostate cancer, we assessed the expression of COX-2 in benign prostatic hyperplasia (BPH) and prostate cancer samples employing immunohistochemistry. COX-2 was over-expressed in 15 out of 18 (83%) prostate cancer samples whereas it was detected in only 22% (4 of 18) paired benign tissues. The intensity of immunostaining correlated with the tumor grading. In addition, COX-2 was expressed in 7 of the 22 (32%) BPH samples examined. The significance a COX-2 expression in the BPH samples is not known at present. This data suggest that COX-2 is over-expressed in prostate cancer and COX-2 inhibitors may be useful in combination chemotherapy or chemoprevention for prostate cancer.

  20. Estrogen receptors in the human male bladder, prostatic urethra, and prostate. An immunohistochemical and biochemical study

    DEFF Research Database (Denmark)

    Bødker, A; Balslev, E; Juul, B R;


    The distribution and quantity of estrogen receptors (ERs) in the human male bladder, prostatic urethra and the prostate were studied in eight males with recurrent papillomas of the bladder or monosymptomatic hematuria (median age 61 years), 14 men undergoing transurethral resection due to benign...... prostatic hyperplasia (median age 70 years), and nine men undergoing cystectomy due to malignant tumour of the bladder (median age 70 years). In the first group of patients, biopsies for immunohistochemical examination were obtained from the bladder vault, bottom, both side-walls, the trigone area......, and the mid-portion of the prostatic urethra, and in the second group from three locations of the prostatic urethra (bladder neck, mid-portion and veramontanum). In the third group, tissue specimens were taken from the vault of the bladder, prostatic urethra, and the prostate, for immunohistochemical as well...

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

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    Claudio Festuccia


    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.

  2. Prostate cancer outcome in Burkina Faso

    Directory of Open Access Journals (Sweden)

    Yameogo Clotaire


    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. (United States)

    Stefanov, Miroslav


    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.

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

    Directory of Open Access Journals (Sweden)

    Pascoe Abigail C


    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.

  5. Emphysematous prostatitis in renal transplant

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    Krishnaswamy Sampathkumar


    Full Text Available Urinary tract infections are common following renal transplant. The spectrum varies from asymptomatic bacteriuria to septicemia. Gas-producing infections of the urinary tract are rare but tend to have a grave prognosis when they do occur. We report a 57-year-old gentleman who underwent a renal transplant 20 months earlier. He presented to us with fever and dysuria. Clinical examination revealed a febrile and ill-looking patient with severe graft tenderness. An emergency pelvic CT scan revealed presence of emphysematous prostatitis, cystitis and pyelitis. Urine and blood cultures grew E. coli . Endoscopic abscess drainage was done and antibiotics given but he succumbed to his illness due to multiorgan failure within 48h. This is the first reported case of emphysematous prostatitis in a renal allograft recipient.

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

    Institute of Scientific and Technical Information of China (English)

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


    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.

  7. Ornithine Decarboxylase Activity Is Required for Prostatic Budding in the Developing Mouse Prostate.

    Directory of Open Access Journals (Sweden)

    Melissa Gamat

    Full Text Available The prostate is a male accessory sex gland that produces secretions in seminal fluid to facilitate fertilization. Prostate secretory function is dependent on androgens, although the mechanism by which androgens exert their effects is still unclear. Polyamines are small cationic molecules that play pivotal roles in DNA transcription, translation and gene regulation. The rate-limiting enzyme in polyamine biosynthesis is ornithine decarboxylase, which is encoded by the gene Odc1. Ornithine decarboxylase mRNA decreases in the prostate upon castration and increases upon administration of androgens. Furthermore, testosterone administered to castrated male mice restores prostate secretory activity, whereas administering testosterone and the ornithine decarboxylase inhibitor D,L-α-difluromethylornithine (DFMO to castrated males does not restore prostate secretory activity, suggesting that polyamines are required for androgens to exert their effects. To date, no one has examined polyamines in prostate development, which is also androgen dependent. In this study, we showed that ornithine decarboxylase protein was expressed in the epithelium of the ventral, dorsolateral and anterior lobes of the adult mouse prostate. Ornithine decarboxylase protein was also expressed in the urogenital sinus (UGS epithelium of the male and female embryo prior to prostate development, and expression continued in prostatic epithelial buds as they emerged from the UGS. Inhibiting ornithine decarboxylase using DFMO in UGS organ culture blocked the induction of prostatic buds by androgens, and significantly decreased expression of key prostate transcription factor, Nkx3.1, by androgens. DFMO also significantly decreased the expression of developmental regulatory gene Notch1. Other genes implicated in prostatic development including Sox9, Wif1 and Srd5a2 were unaffected by DFMO. Together these results indicate that Odc1 and polyamines are required for androgens to exert their

  8. Tumor-associated Endo180 requires stromal-derived LOX to promote metastatic prostate cancer cell migration on human ECM surfaces. (United States)

    Caley, Matthew P; King, Helen; Shah, Neel; Wang, Kai; Rodriguez-Teja, Mercedes; Gronau, Julian H; Waxman, Jonathan; Sturge, Justin


    The diverse composition and structure of extracellular matrix (ECM) interfaces encountered by tumor cells at secondary tissue sites can influence metastatic progression. Extensive in vitro and in vivo data has confirmed that metastasizing tumor cells can adopt different migratory modes in response to their microenvironment. Here we present a model that uses human stromal cell-derived matrices to demonstrate that plasticity in tumor cell movement is controlled by the tumor-associated collagen receptor Endo180 (CD280, CLEC13E, KIAA0709, MRC2, TEM9, uPARAP) and the crosslinking of collagen fibers by stromal-derived lysyl oxidase (LOX). Human osteoblast-derived and fibroblast-derived ECM supported a rounded 'amoeboid-like' mode of cell migration and enhanced Endo180 expression in three prostate cancer cell lines (PC3, VCaP, DU145). Genetic silencing of Endo180 reverted PC3 cells from their rounded mode of migration towards a bipolar 'mesenchymal-like' mode of migration and blocked their translocation on human fibroblast-derived and osteoblast-derived matrices. The concomitant decrease in PC3 cell migration and increase in Endo180 expression induced by stromal LOX inhibition indicates that the Endo180-dependent rounded mode of prostate cancer cell migration requires ECM crosslinking. In conclusion, this study introduces a realistic in vitro model for the study of metastatic prostate cancer cell plasticity and pinpoints the cooperation between tumor-associated Endo180 and the stiff microenvironment imposed by stromal-derived LOX as a potential target for limiting metastatic progression in prostate cancer.

  9. Negative control of epithelial cell proliferation by prostatic stroma

    NARCIS (Netherlands)

    A. Kooistra (Anko)


    textabstractProstatic diseases are rather frequently occurring disorders in the male population. Prostatic adenoma -better known as benign prostatic hyperplasia (BPH)- is the most common benign neoplasm in men. Prostate cancer is the most commonly diagnosed malignancy in men and second leading cause

  10. MRI of the prostate: potential role of robots

    NARCIS (Netherlands)

    Fütterer, Jurgen J.; Misra, Sarthak; Macura, Katarzyna J.


    Prostate cancer is the most frequently diagnosed malignancy in the male population. Transrectal ultrasound- guided biopsy is still the imaging modality of choice in detecting prostate cancer. However, with prostate cancer being detected at an earlier stage, most prostate cancers tend to be isoechoic

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

    NARCIS (Netherlands)

    M.J. Roobol-Bouts (Monique)


    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

  12. Impact of Individual Risk Assessment on Prostate Cancer Diagnosis

    NARCIS (Netherlands)

    H.A. van Vugt (Heidi)


    textabstractCurrent prostate-specific antigen screening practice leads to two important unwanted side effects; first of all screening induces many unnecessary prostate biopsies and secondly it leads to overdiagnosis and overtreatment of prostate cancer. The large amount of unnecessary prostate biops

  13. Metabolomic Profiling of Prostate Cancer Progression During Active Surveillance (United States)


    cancer or a history of transurethral resection of the prostate (TURP) for benign prostatic hypertrophy are excluded. Somewhat surprisingly...AD_________________ Award Number: W81XWH-11-1-0451 TITLE: Metabolomic Profiling of Prostate Cancer...29 September 2012 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Metabolomic Profiling of Prostate Cancer Progression During Active Surveillance 5b

  14. Primary staging of prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Jager, G.J. [Dept. of Radiology, Univ. Hospital, Nijmegen (Netherlands); Barentz, J.O. [Dept. of Radiology, Univ. Hospital, Nijmegen (Netherlands); Ruijter, E.T.G. [Dept. of Urology, Univ. Hospital, Nijmegen (Netherlands)]|[Dept. of Pathology, Univ. Hospital, Nijmegen (Netherlands); Rosette, J.J.M.C.H. de la [Dept. of Urology, Univ. Hospital, Nijmegen (Netherlands); Oosterhof, G.O.N. [Dept. of Urology, Univ. Hospital, Nijmegen (Netherlands)


    Staging prostate cancer is a systematic classification of the extent of disease based on clinical and pathological criteria. Despite general acceptance of the TNM staging system, a lot of controversy and uncertainty with respect to staging still exists. This paper gives an overview of differnt staging modalities and emphasizes the need for incorporation of prognostic factors, such as tumour grade and volume, in the staging system. (orig.)

  15. Prostate Cancer Pathology Resource Network (United States)


    May after a long illness. Her responsibilities have been subsumed by Helen Fedor and Medha Darshan, and will be taken over by a Clinical...of the Prostate Cancer Biorepository Network Medha Darshan1*, Qizhi Zheng1*, Helen L. Fedor1*, Nicolas Wyhs2, Srinivasan Yegnasubramanian2...samples using the DNeasy Blood &Tissue kit (Qiagen). DNA quantification and 260:280 ratios were obtained by Nanodrop (Thermo Fisher Scientific Inc

  16. ESUR prostate MR guidelines 2012

    Energy Technology Data Exchange (ETDEWEB)

    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)


    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.)

  17. Aging Men and Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Thompson B


    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.

  18. Nocturia and benign prostatic hyperplasia

    Directory of Open Access Journals (Sweden)

    Laketić Darko


    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.

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

    DEFF Research Database (Denmark)

    Brasso, K; Iversen, Peter


    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 demonstrated to cause significant morbidity. Furthermore, the patients suffered significant excess mortality and loss of life expectancy....

  20. Carbohydrate structure and differential binding of prostate specific antigen to Maackia amurensis lectin between prostate cancer and benign prostate hypertrophy. (United States)

    Ohyama, Chikara; Hosono, Masahiro; Nitta, Kazuo; Oh-eda, Masayoshi; Yoshikawa, Kazuyuki; Habuchi, Tomonori; Arai, Yoichi; Fukuda, Minoru


    Serum prostate-specific antigen (PSA) assay is widely used for detection of prostate cancer. Because PSA is also synthesized from normal prostate, false positive diagnosis cannot be avoided by the conventional serum PSA test. To apply the cancer-associated carbohydrate alteration to the improvement of PSA assay, we first elucidated the structures of PSA purified from human seminal fluid. The predominant core structure of N-glycans of seminal fluid PSA was a complex type biantennary oligosaccharide and was consistent with the structure reported previously. However, we found the sialic acid alpha2-3 galactose linkage as an additional terminal carbohydrate structure on seminal fluid PSA. We then analyzed the carbohydrate moiety of serum PSA from the patients with prostate cancer and benign prostate hypertrophy using lectin affinity chromatography. Lectin binding was assessed by lectin affinity column chromatography followed by determining the amount of total and free PSA. Concanavalin A, Lens culinaris, Aleuria aurantia, Sambucus nigra, and Maackia amurensis lectins were tested for their binding to the carbohydrates on PSA. Among the lectins examined, the M. amurensis agglutinin-bound fraction of free serum PSA is increased in prostate cancer patients compared to benign prostate hypertrophy patients. The binding of PSA to M. amurensis agglutinin, which recognizes alpha2,3-linked sialic acid, was also confirmed by surface plasmon resonance analysis. These results suggest that the differential binding of free serum PSA to M. amurensis agglutinin lectin between prostate cancer and benign prostate hypertrophy could be a potential measure for diagnosis of prostate cancer.

  1. Radiological Findings of Prostatic Arterial Anatomy for Prostatic Arterial Embolization: Preliminary Study in 55 Chinese Patients with Benign Prostatic Hyperplasia.

    Directory of Open Access Journals (Sweden)

    Guodong Zhang

    Full Text Available To describe the prostatic arterial supply using Cone-beam computed tomography (CT and digital subtraction angiography (DSA before prostatic arterial embolization (PAE for benign prostatic hyperplasia (BPH.In a retrospective study from January 2012 to January 2014, 55 male patients (110 hemipelves with BPH who underwent PAE were evaluated by Cone-beam CT in addition to pelvic DSA during embolization planning. Each hemipelvis was evaluated regarding the number of prostatic arteries (PA and their origins, diameters, territorial perfusion, and anastomoses with adjacent arteries.A total of 114 PAs were identified in 110 hemipelves. There was one PA in 96.4% of the hemipelves (n=106, and two independent PAs in the other 3.6% (n=4. The PA was found to originate from the anterior trunk of the internal iliac artery in 39.5% of cases (n=45 , from the superior vesical artery in 32.6% (n=37, and from the internal pudendal artery in 27.9% of cases (n=32. Extra-prostatic anastomoses between PA and adjacent arteries were found in 39.1% of hemipelves (n=43. Intra-prostatic anastomoses between PAs and contra-lateral prostatic branches were found in 61.8% of hemipelves (n=68. In 67.3% of our study population (n=37, the prostate was dominantly supplied via a unilateral PA.The prostatic vascularization is complex with frequent anatomic variations. Knowledge of the vascular anatomy of the prostate may provide indications for planning PAE and avoiding nontarget embolization.

  2. ETS fusion genes in prostate cancer. (United States)

    Gasi Tandefelt, Delila; Boormans, Joost; Hermans, Karin; Trapman, Jan


    Prostate cancer is very common in elderly men in developed countries. Unravelling the molecular and biological processes that contribute to tumor development and progressive growth, including its heterogeneity, is a challenging task. The fusion of the genes ERG and TMPRSS2 is the most frequent genomic alteration in prostate cancer. ERG is an oncogene that encodes a member of the family of ETS transcription factors. At lower frequency, other members of this gene family are also rearranged and overexpressed in prostate cancer. TMPRSS2 is an androgen-regulated gene that is preferentially expressed in the prostate. Most of the less frequent ETS fusion partners are also androgen-regulated and prostate-specific. During the last few years, novel concepts of the process of gene fusion have emerged, and initial experimental results explaining the function of the ETS genes ERG and ETV1 in prostate cancer have been published. In this review, we focus on the most relevant ETS gene fusions and summarize the current knowledge of the role of ETS transcription factors in prostate cancer. Finally, we discuss the clinical relevance of TMRPSS2-ERG and other ETS gene fusions in prostate cancer.

  3. Prostate cancer is not breast cancer

    Directory of Open Access Journals (Sweden)

    Ajit Venniyoor


    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.

  4. Urodynamic implications of benign prostatic hyperplasia

    DEFF Research Database (Denmark)

    Jensen, K M; Andersen, J T


    By the age of 60, about 70% of men have developed benign prostatic hyperplasia (BPH), and 85%-95% of these have symptomatic dysfunction of the lower urinary tract, 10%-20% undergoing prostatectomy. Although transurethral resection of the prostate is generally considered to be a safe and effective...

  5. Prostatic tissue ectopia in the rectum

    Institute of Scientific and Technical Information of China (English)

    WU Xin-lin; SHI Lin; ZHAO Li-zhen; WANG Jing-yuan; DONG Pei-de; XIA Yang-zhi


    @@ Areview of the literature on ectopic prostatic tissue reveals about 200 reports dating back to as early as 1894. The presence of prostate tissue outside the genitourinary system is extremely rare. It is usually incidentally found in surgical pathology and autopsy.

  6. Relationship between age and prostate size

    Institute of Scientific and Technical Information of China (English)

    Shi-Jun Zhang; Hai-Ning Qian; Yan Zhao; Kai Sun; Hui-Qing Wang; Guo-Qing Liang; Feng-Hua Li; Zheng Li


    In a community-based study,the relationship between age and human prostate size was investigated in a population of men between the ages of 40 and 70 years to determine the normal prostate increase curve equation.One thousand male volunteers were randomly recruited from the Shanghai community,and the length,width,height,volume of the transition zone (TZ) and the whole prostates were measured by transrectal ultrasound (TRUS).Each volunteer was evaluated by the International Prostate Symptom Score (IPSS).Among those who completed the examination,the mean prostate parameters were all positively associated with increased age.There were statistically significant differences between each age group (P<0.05).The mean transition zone volume (TZV) had a higher increase rate with age than the mean total prostate volume (TPV),indicating that the enlargement of the TZ contributed the most to the increase in TPV.While all prostate parameters were positively correlated with the IPSS,the strongest correlation was associated with the TZ length (TZL) and TZV.The growth curve equations for prostate width,height and length were also positively associated with increasing age.

  7. Discovery and validation of prostate cancer biomarkers

    NARCIS (Netherlands)

    F.H. Jansen (Flip)


    textabstractThe prostate, derived from the Greek word προστάτης – prostates, meaning “the one who stands before”, is a walnut-sized exocrine gland, part of the male genitourinary tract. It produces and stores an alkaline fluid, which liquefies the semen and prolongs the life-span of the spermatozoa.

  8. [Practice guideline 'Prostate cancer: diagnosis and treatment'

    NARCIS (Netherlands)

    Reijke, T.M. de; Battermann, J.J.; Moorselaar, R.J.A. van; Jong, IJ de; Visser, A.P.; Burgers, J.S.


    --A national, multidisciplinary practice guideline was developed concerning diagnosis and treatment of patients with prostate cancer. Because of the lack of sufficient scientific evidence at this moment no practice guideline on screening is included. --The diagnosis of prostate cancer is made by tra

  9. Effects of Prostate Cancer Screening and Treatment

    NARCIS (Netherlands)

    E.M. Wever (Elisabeth)


    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

  10. Chemotherapeutic prevention studies of prostate cancer

    DEFF Research Database (Denmark)

    Djavan, Bob; Zlotta, Alexandre; Schulman, Claude;


    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 natur...

  11. Genetically engineered mouse models of prostate cancer

    NARCIS (Netherlands)

    Nawijn, Martijn C.; Bergman, Andreas M.; van der Poel, Henk G.


    Objectives: Mouse models of prostate cancer are used to test the contribution of individual genes to the transformation process, evaluate the collaboration between multiple genetic lesions observed in a single tumour, and perform preclinical intervention studies in prostate cancer research. Methods:

  12. Prostate cancer screening: tests and algorithms

    NARCIS (Netherlands)

    M.J. Roobol-Bouts (Monique)


    textabstractAlthough the concept of early detection of cancer sounds intuitively logical it is not automatically so in the case of prostate cancer despite the fact that the data on incidence and mortality show that it is an important health problem. The fact that prostate cancer is in general a s

  13. Genomic rearrangements of PTEN in prostate cancer

    Directory of Open Access Journals (Sweden)

    Sopheap ePhin


    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.

  14. Toll-like Receptors and Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Shu eZhao


    Full Text Available Prostate cancer is the second leading cause of cancer-related death in men after lung cancer. Immune responses clearly play a critical role in the tumorigenesis and in the efficacy of radiation therapy and chemotherapy in prostate cancer; however, the underlying molecular mechanisms are still poorly understood. Toll-like receptors (TLRs are a well-known family of pattern recognition receptors that play a key role in host immune system. Recent studies demonstrate that there are links between TLRs and cancer; however, the function and biological importance of TLRs in prostate cancer seems complex. To elucidate the role of TLRs and innate immunity in prostate cancer might provide us with a better understanding of the molecular mechanisms of this disease. Moreover, utilizing the agonists or antagonists of TLRs might represent a promising new strategy against prostate cancer. In this review, we summarize recent advances on the studies of association between TLR signaling and prostate cancer, TLR polymorphisms and prostate cancer risk, and provide some insights about TLRs as potential targets for prostate cancer immunotherapy.

  15. Primary care perspectives on prostate cancer screening. (United States)

    Skolarus, Ted A; Holmes-Rovner, Margaret; Northouse, Laurel L; Fagerlin, Angela; Garlinghouse, Carol; Demers, Raymond Y; Rovner, David R; Darwish-Yassine, May; Wei, John T


    Although the effectiveness of prostate cancer screening is controversial, screening rates have risen dramatically among primary care providers in the United States. The authors' findings suggest more collaboration among primary care and specialty organizations, especially with respect to decision aid endorsement, is needed to achieve more discriminatory and patient-centered prostate cancer screening.

  16. Prostatic Abscess Caused by Streptococcus mutans

    Directory of Open Access Journals (Sweden)

    Chau Nguyen


    Full Text Available The first reported case of prostatic abscess caused by Streptococcus mutans isolated in pure culture is described. Urethral dilation for obstruction was unsuccessful, so suprapubic cystostomy was performed. Perineal aspiration under ultrasonic guidance resulted in 10 mL of pus containing pure Strep mutans. Diagnosis of prostatic abscess is difficult since the clinical manifestations are nonspecific.

  17. Regulation of the Prostate Cancer Tumor Microenvironment (United States)


    regulatory Tcells (Tregs) and Th17 cells [6,7]. Nonetheless, the clinical importance of the immune system in prostate cancer is borne out by Phenotypic analysis of prostate-infiltrating lympho- cytes reveals TH17 and Treg skewing. Clin Cancer Res 2008;14:3254–3261. 7. Rigamonti N

  18. Active Surveillance For Low Risk Prostate Cancer

    NARCIS (Netherlands)

    R.C.N. van den Bergh (Roderick)


    textabstractThe prostate is part of the male genitourinary tract. It is a walnut-sized gland, located underneath the urinary bladder, enveloping the proximal part of the urethra. The main function of the prostate is the excretion of a fl uid that forms part of the semen, but it also has an important

  19. FGF Signaling in Prostate Cancer Progression

    Institute of Scientific and Technical Information of China (English)

    Nora M. NAVONE


    @@ 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. Widespread telomere instability in prostatic lesions. (United States)

    Tu, LiRen; Huda, Nazmul; Grimes, Brenda R; Slee, Roger B; Bates, Alison M; Cheng, Liang; Gilley, David


    A critical function of the telomere is to disguise chromosome ends from cellular recognition as double strand breaks, thereby preventing aberrant chromosome fusion events. Such chromosome end-to-end fusions are known to initiate genomic instability via breakage-fusion-bridge cycles. Telomere dysfunction and other forms of genomic assault likely result in misregulation of genes involved in growth control, cell death, and senescence pathways, lowering the threshold to malignancy and likely drive disease progression. Shortened telomeres and anaphase bridges have been reported in a wide variety of early precursor and malignant cancer lesions including those of the prostate. These findings are being extended using methods for the analysis of telomere fusions (decisive genetic markers for telomere dysfunction) specifically within human tissue DNA. Here we report that benign prostatic hyperplasia (BPH), high-grade prostatic intraepithelial neoplasia (PIN), and prostate cancer (PCa) prostate lesions all contain similarly high frequencies of telomere fusions and anaphase bridges. Tumor-adjacent, histologically normal prostate tissue generally did not contain telomere fusions or anaphase bridges as compared to matched PCa tissues. However, we found relatively high levels of telomerase activity in this histologically normal tumor-adjacent tissue that was reduced but closely correlated with telomerase levels in corresponding PCa samples. Thus, we present evidence of high levels of telomere dysfunction in BPH, an established early precursor (PIN) and prostate cancer lesions but not generally in tumor adjacent normal tissue. Our results suggest that telomere dysfunction may be a common gateway event leading to genomic instability in prostate tumorigenesis. .

  1. Telomere Length Polymorphisms: A Potential Factor Underlying Increased Risk of Prostate Cancer in African American Men and Familial Prostate Cancer (United States)


    markers to allow specific identification of prostate cancer cells in urine cytology specimens. 10 Role: PI Patrick C. Walsh Prostate Cancer Research...Detection of Prostate Cancer in Urine by Multiplex Immunofluorescence and Telomere FISH – Guiding Clinical Decisions Following Negative Prostate

  2. The expression of receptors for estrogen and epithelial growth factor in the male rabbit prostate and prostatic urethra following castration

    DEFF Research Database (Denmark)

    Bødker, A; Balslev, E; Iversen, H G


    were included as controls. In the control group, ERs were found in the urothelial lining and lamina propria of the prostatic urethra, and in the prostatic stroma. EGF receptors were demonstrated in the epithelial lining of the prostatic urethra and the glandular epithelium of the prostate. Following...

  3. Oxidative stress in benign prostate hyperplasia. (United States)

    Zabaiou, N; Mabed, D; Lobaccaro, J M; Lahouel, M


    To assess the status of oxidative stress in benign prostate hyperplasia, a very common disease in older men which constitutes a public health problem in Jijel, prostate tissues were obtained by transvesical adenomectomy from 10 men with benign prostate hyperplasia. We measured the cytosolic levels of malondialdehyde (MDA) and glutathione (GSH) and cytosolic enzyme activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione S-transferase. The development of benign prostate hyperplasia is accompanied by impaired oxidative status by increasing levels of MDA, depletion of GSH concentrations and a decrease in the activity of all the antioxidant enzymes studied. These results have allowed us to understand a part of the aetiology of benign prostate hyperplasia related to oxidative stress.

  4. Vitamin D, Sunlight and Prostate Cancer Risk

    Directory of Open Access Journals (Sweden)

    Krishna Vanaja Donkena


    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.

  5. Molecular imaging of prostate cancer with PET. (United States)

    Jadvar, Hossein


    Molecular imaging is paving the way for precision and personalized medicine. In view of the significant biologic and clinical heterogeneity of prostate cancer, molecular imaging is expected to play an important role in the evaluation of this prevalent disease. The natural history of prostate cancer spans from an indolent localized process to biochemical relapse after radical treatment with curative intent to a lethal castrate-resistant metastatic disease. The ongoing unraveling of the complex tumor biology of prostate cancer uniquely positions molecular imaging with PET to contribute significantly to every clinical phase of prostate cancer evaluation. The purpose of this article was to provide a concise review of the current state of affairs and potential future developments in the diagnostic utility of PET in prostate cancer.

  6. Prostate biopsy tracking with deformation estimation

    CERN Document Server

    Baumann, Michael; Daanen, Vincent; Troccaz, Jocelyne


    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 ...

  7. Pten Regulates Epithelial Cytodifferentiation during Prostate Development

    DEFF Research Database (Denmark)

    Lokody, Isabel B; Francis, Jeffrey C; Gardiner, Jennifer R;


    Gene expression and functional studies have indicated that the molecular programmes involved in prostate development are also active in prostate cancer. PTEN has been implicated in human prostate cancer and is frequently mutated in this disease. Here, using the Nkx3.1:Cre mouse strain and a genetic...... deletion approach, we investigate the role of Pten specifically in the developing mouse prostate epithelia. In contrast to its role in other developing organs, this gene is dispensable for the initial developmental processes such as budding and branching. However, as cytodifferentiation progresses...... that are shared with Pten mutant prostate cancer models, including a decrease in androgen receptor regulated genes. In depth analysis of the phenotype of these mice during development revealed that loss of Pten leads to the precocious differentiation of epithelial cells towards a luminal cell fate. This study...

  8. Review of selenium and prostate cancer prevention. (United States)

    Yang, Lei; Pascal, Mouracade; Wu, Xiao-Hou


    Prostate cancer is the most common malignancy in men in the United States. Surgery or radiation are sometimes unsatisfactory treatments because of the complications such as incontinence or erectile dysfunction. Selenium was found to be effective to prevent prostate cancer in the Nutritional Prevention of Cancer Trial (NPC), which motivated two other clinical trials: the Selenium and Vitamin E Cancer Prevention Trial (SELECT) and a Phase III trial of selenium to prevent prostate cancer in men with high-grade prostatic intraepithelial neoplasia. However, these two trials failed to confirm the results of the NPC trial and indicated that the selenium may not be preventive of prostate cancer. In this article we review the three clinical trials and discuss some different points which might be potential factors underlying variation in results obtained.

  9. National Cancer Institute Prostate Cancer Genetics Workshop. (United States)

    Catalona, William J; Bailey-Wilson, Joan E; Camp, Nicola J; Chanock, Stephen J; Cooney, Kathleen A; Easton, Douglas F; Eeles, Rosalind A; FitzGerald, Liesel M; Freedman, Matthew L; Gudmundsson, Julius; Kittles, Rick A; Margulies, Elliott H; McGuire, Barry B; Ostrander, Elaine A; Rebbeck, Timothy R; Stanford, Janet L; Thibodeau, Stephen N; Witte, John S; Isaacs, William B


    Compelling evidence supports a genetic component to prostate cancer susceptibility and aggressiveness. Recent genome-wide association studies have identified more than 30 single-nucleotide polymorphisms associated with prostate cancer susceptibility. It remains unclear, however, whether such genetic variants are associated with disease aggressiveness--one of the most important questions in prostate cancer research today. To help clarify this and substantially expand research in the genetic determinants of prostate cancer aggressiveness, the first National Cancer Institute Prostate Cancer Genetics Workshop assembled researchers to develop plans for a large new research consortium and patient cohort. The workshop reviewed the prior work in this area and addressed the practical issues in planning future studies. With new DNA sequencing technology, the potential application of sequencing information to patient care is emerging. The workshop, therefore, included state-of-the-art presentations by experts on new genotyping technologies, including sequencing and associated bioinformatics issues, which are just beginning to be applied to cancer genetics.

  10. Role of androgen receptor in prostatic neoplasia versus hyperplasia

    Directory of Open Access Journals (Sweden)

    Irma Husain


    Discussion: AR nuclear expression is present in benign and malignant prostatic epithelium. In this study, cases of prostate cancer demonstrated a higher staining intensity for AR when compared with BPH. The intensity of AR staining in prostate cancer significantly reduces as the Gleason grade of the tumor increases. The staining intensity for AR was heterogeneous specifically in cases of prostate cancer. Our results indicate that AR maybe considered as a prognostic marker in prostate cancer.

  11. Prostatic MR imaging. Accuracy in differentiating cancer from other prostatic disorders

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    Ikonen, S.; Kivisaari, L.; Tervahartiala, P. [Helsinki Univ. Central Hospital (Finland). Dept of Radiology; Vehmas, T. [Finnish Inst. of Occupational Health, Helsinki (Finland); Taari, K.; Rannikko, S. [Helsinki Univ. Central Hospital (Finland). Dept of Urology


    Purpose: We assessed the accuracy of MR imaging in differentiating between cancer and other prostatic disorders, and evaluated the diagnostic criteria for various prostatic diseases. Material and Methods: A total of 74 endorectal coil MR studies were performed on 72 patients. Twenty patients had prostatic cancer, 20 benign prostatic hyperplasia (BPH), 4 acute bacterial prostatitis, 5 chronic bacterial prostatitis (2 also belonging to the previous category), 19 chronic non-bacterial prostatitis/chronic pelvic pain syndrome, and 6 were symptomless voluntary controls. All studies were interpreted by two experienced radiologists in random order. Radiologists were blinded to all clinical data including the age of the patients. Based on MR findings, both radiologists filled in a form covering diagnostic criteria and diagnosis. Results: Accuracy in diagnosing prostate cancer was 74%. Sensitivity was 50% and specificity 83%, and positive and negative predictive values were 53 and 82%, respectively. Bacterial prostatitis showed some features similar to carcinoma. Abundant BPH rendered cancer detection more difficult. No diagnostic criterion was clearly better than the others. Interobserver agreement on the MR diagnosis ranged from moderate to good. Conclusion: Without knowledge of accurate clinical data, MR seems to be too insensitive in detecting prostate cancer to be used as a primary diagnostic tool.

  12. GLI1 confers profound phenotypic changes upon LNCaP prostate cancer cells that include the acquisition of a hormone independent state.

    Directory of Open Access Journals (Sweden)

    Sandeep K Nadendla

    Full Text Available The GLI (GLI1/GLI2 transcription factors have been implicated in the development and progression of prostate cancer although our understanding of how they actually contribute to the biology of these common tumours is limited. We observed that GLI reporter activity was higher in normal (PNT-2 and tumourigenic (DU145 and PC-3 androgen-independent cells compared to androgen-dependent LNCaP prostate cancer cells and, accordingly, GLI mRNA levels were also elevated. Ectopic expression of GLI1 or the constitutively active ΔNGLI2 mutant induced a distinct cobblestone-like morphology in LNCaP cells that, regarding the former, correlated with increased GLI2 as well as expression of the basal/stem-like markers CD44, β1-integrin, ΔNp63 and BMI1, and decreased expression of the luminal marker AR (androgen receptor. LNCaP-GLI1 cells were viable in the presence of the AR inhibitor bicalutamide and gene expression profiling revealed that the transcriptome of LNCaP-GLI1 cells was significantly closer to DU145 and PC-3 cells than to control LNCaP-pBP (empty vector cells, as well as identifying LCN2/NGAL as a highly induced transcript which is associated with hormone independence in breast and prostate cancer. Functionally, LNCaP-GLI1 cells displayed greater clonal growth and were more invasive than control cells but they did not form colonies in soft agar or prostaspheres in suspension suggesting that they do not possess inherent stem cell properties. Moreover, targeted suppression of GLI1 or GLI2 with siRNA did not reverse the transformed phenotype of LNCaP-GLI1 cells nor did double GLI1/GLI2 knockdowns activate AR expression in DU145 or PC-3 cells. As such, early targeting of the GLI oncoproteins may hinder progression to a hormone independent state but a more detailed understanding of the mechanisms that maintain this phenotype is required to determine if their inhibition will enhance the efficacy of anti-hormonal therapy through the induction of a luminal

  13. Prostate size correlates with fasting blood glucose in non-diabetic benign prostatic hyperplasia patients with normal testosterone levels. (United States)

    Kim, Won Tae; Yun, Seok Joong; Choi, Young Deuk; Kim, Gi-Young; Moon, Sung-Kwon; Choi, Yung Hyun; Kim, Isaac Yi; Kim, Wun-Jae


    We evaluated the correlations between BMI, fasting glucose, insulin, testosterone level, insulin resistance, and prostate size in non-diabetic benign prostatic hyperplasia (BPH) patients with normal testosterone levels. Data from 212 non-diabetic BPH patients with normal testosterone levels, who underwent transurethral resection of the prostate (TURP) due to medical treatment failure, were evaluated retrospectively. Patients with prostate specific antigen (PSA) levels of ≥ 3 ng/mL underwent multicore transrectal prostate biopsy before TURP to rule out prostate cancer. Patients with diabetes mellitus (DM) or serum testosterone levels of Prostate size correlated positively with age (r = 0.227, P 0.05). Testosterone level inversely correlated with BMI (r = -0.327, P prostate size, PSA, or fasting glucose level (each P > 0.05). Upon multiple adjusted linear regression analysis, prostate size correlated with elevated PSA (P prostate hyperplasia.

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