The Experts below are selected from a list of 45543 Experts worldwide ranked by ideXlab platform
Axel Semjonow - One of the best experts on this subject based on the ideXlab platform.
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Twenty Years of PSA: From Prostate Antigen to Tumor Marker
Reviews in urology, 2007Co-Authors: De Angelis G, H. G. Rittenhouse, S. D. Mikolajczyk, Blair Shamel L, Axel SemjonowAbstract:The measurement of Prostate-specific Antigen in serum is credited with dramatic advances in the early detection of men with prostatic carcinoma. This report summarizes the history of biochemical research and the current understanding and application of Prostate-specific Antigen in Prostate cancer diagnostics.
Douglas G Mcneel - One of the best experts on this subject based on the ideXlab platform.
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An aberrant Prostate Antigen–specific immune response causes prostatitis in mice and is associated with chronic prostatitis in humans
The Journal of clinical investigation, 2009Co-Authors: Yafei Hou, Douglas G Mcneel, Jason Devoss, Vinh Dao, Serena S. Kwek, Jeff Simko, Mark S. Anderson, Lawrence FongAbstract:Chronic prostatitis is a common disease of unclear etiology and has no specific treatment. Mice deficient in the expression of the autoimmune regulator (Aire) gene, which are defective in thymic expression of self Antigens and central tolerance, develop spontaneous prostatitis. In this study, we found that Aire-deficient mice developed spontaneous B and T cell immune responses to a Prostate autoAntigen, seminal vesicle secretory protein 2 (SVS2), which we believe to be novel. We show that thymic expression of this self Antigen was Aire dependent. Moreover, prostatitis was induced in WT mice through immunization with SVS2, demonstrating that immunity to SVS2 was sufficient to induce prostatitis. The clinical relevance of this Antigen was highlighted by our observation that patients with chronic prostatitis possessed specific autoantibodies against the human SVS2-like seminal vesicle protein semenogelin. These results provide direct evidence that spontaneous chronic prostatitis is an autoimmune disease and is regulated by both central and peripheral tolerance. Moreover, SVS2 and semenogelin are among the relevant autoAntigens in mice and humans, respectively.
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plasmid dna vaccine encoding prostatic acid phosphatase is effective in eliciting autologous Antigen specific cd8 t cells
Cancer Immunology Immunotherapy, 2007Co-Authors: Laura E Johnson, Thomas Frye, Nachimuthu Chinnasamy, Dhanalakshmi Chinnasamy, Douglas G McneelAbstract:Prostatic acid phosphatase (PAP) is a Prostate cancer tumor Antigen and a Prostate-specific protein shared by rats and humans. Previous studies indicated that Copenhagen rats immunized with a recombinant vaccinia virus expressing human PAP (hPAP) developed PAP-specific cytotoxic T cells (CTL) with cross reactivity to rat PAP (rPAP) and evidence of Prostate inflammation. Viral delivery of vaccine Antigens is an active area of clinical investigation. However, a potential difficulty with viral-based immunizations is that immune responses elicited to the viral vector might limit the possibility of multiple immunizations. In this paper, we investigate the ability of another genetic immunization method, a DNA vaccine encoding PAP, to elicit Antigen-specific CD8+ T cell immune responses. Specifically, Lewis rats were immunized with either a plasmid DNA-based (pTVG-HP) or vaccinia-based (VV-HP) vaccine each encoding hPAP. We determined that rats immunized with a DNA vaccine encoding hPAP developed a Th1-biased immune response as indicated by proliferating PAP-specific CD4+ and CD8+ cells and IFNγ production. Rats immunized with vaccinia virus encoding PAP did not develop a PAP-specific response unless boosted with a heterologous vaccination scheme. Most importantly, multiple immunizations with a DNA vaccine encoding the rat PAP homologue (pTVG-RP) could overcome peripheral self-tolerance against rPAP and generate a Th1-biased Antigen-specific CD4+ and CD8+ T cell response. Overall, DNA vaccines provide a safe and effective method of generating Prostate Antigen-specific T cell responses. These findings support the investigation of PAP-specific DNA vaccines in human clinical trials.
Ole Forsberg - One of the best experts on this subject based on the ideXlab platform.
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Identification of Prostate infiltrating lymphocytes and activation of Prostate Antigen-specific T cells isolated from Prostate cancer patients
2009Co-Authors: Ole Forsberg, Hans Hamberg, Thomas H. Tötterman, Magnus EssandAbstract:Although Prostate Antigen-specific CD8+ T lymphocytes have been found both in peripheral blood and in tumor area of Prostate cancer patients there has not yet been any adequate adoptive T lymphocyt ...
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Generation of Therapeutic T Cells for Prostate Cancer
2009Co-Authors: Ole ForsbergAbstract:Although Prostate Antigen-specific CD8+ T lymphocytes have been found both in peripheral blood and in tumor area of Prostate cancer patients there has not yet been any adequate adoptive T lymphocyte transfer trial for Prostate cancer patients. Methods for efficient generation of large number of Prostate Antigen-specific T cells are still lacking. In the present study we isolate and expand Prostate infiltrating lymphocytes (PILs) from resected Prostates by fine needle aspiration of patients with localized Prostate cancer. By using HLA-A*0201-restricted tetramers, specific for the Prostate tumor-associated Antigen epitopes TARP(P5L)4-13, STEAP262-270 and PSA53-61, we were able to identify Prostate Antigen-specific CD8+ PILs in 5 out of 5 patients. Most frequent were STEAP262-270-specific T cells (5/5). Furthermore, by using fast-matured dendritic cells (DCs) transduced with an adenoviral vector encoding the STEAP Antigen we were able to generate CD8+ T cells from peripheral blood of Prostate cancer patients, for three HLA-A*0201-restricted STEAP epitopes simultaneously by one stimulation only. If combined, an effective protocol for generation of Prostate Antigen-specific T cells may be developed.
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High frequency of Prostate Antigen‐directed T cells in cancer patients compared to healthy age‐matched individuals
The Prostate, 2008Co-Authors: Ole Forsberg, Thomas H. Tötterman, Björn Carlsson, Per-uno Malmström, Gustav J. Ullenhag, Magnus EssandAbstract:BACKGROUND. In order to obtain a sustained cytotoxic T lymphocyte (CTL) response against cancer cells it is preferable to have CTLs directed against multiple peptide epitopes from numerous tumor-as ...
De Angelis G - One of the best experts on this subject based on the ideXlab platform.
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Twenty Years of PSA: From Prostate Antigen to Tumor Marker
Reviews in urology, 2007Co-Authors: De Angelis G, H. G. Rittenhouse, S. D. Mikolajczyk, Blair Shamel L, Axel SemjonowAbstract:The measurement of Prostate-specific Antigen in serum is credited with dramatic advances in the early detection of men with prostatic carcinoma. This report summarizes the history of biochemical research and the current understanding and application of Prostate-specific Antigen in Prostate cancer diagnostics.
John D. Hayball - One of the best experts on this subject based on the ideXlab platform.
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Transforming growth factor-β-mediated signaling in T lymphocytes impacts on Prostate-specific immunity and early Prostate tumor progression
Laboratory Investigation, 2009Co-Authors: Kerrilyn R. Diener, Anthony E Woods, Jim Manavis, Michael P Brown, John D. HayballAbstract:T cells are in general tolerant of Prostate-specific tumor Antigens. That Prostate tumor tissue makes transforming growth factor- β (TGF β ) is thought to play a role in the induction of T-cell tolerance within the host and to contribute to tumor progression itself. Here we sought to investigate the influence of TGF β signaling on Prostate Antigen-specific T-cell responses as well as Prostate tumorogenesis in an autochthonous murine model of the disease. The response of naive and activated ovalbumin (OVA) Antigen-specific T cells, which had been rendered incapable of responding to TGF β through T-cell-specific transgenic expression of a dominant-negative variant of the TGF β receptor II (dnTGFRII), was analyzed after adoptive transfer into Prostate OVA-expressing transgenic (POET) mice. The role of TGF β signaling in endogenous T cells in mice, which spontaneously form tumors, was also assessed by monitoring Prostate tumor formation and progression in F1 progeny of productive matings between transgenic adenocarcinoma of the mouse Prostate (TRAMP) and dnTGFRII mice. TGF β -resistant CD8^+ T cells proliferated more and produced IFN γ more readily after OVA stimulation in vitro . OVA-specific T cells did not damage the Prostate gland of POET mice irrespective of TGF β responsiveness. However, ex vivo activation facilitated entry of TGF β -insensitive T cells into the Prostate and was associated with Prostate tissue damage. Early tumor progression was delayed in TRAMP mice that carried endogenous TGF β -insensitive T cells. Together, these results suggest that TGF β -signaling represses CD8^+ T-cell responses to a Prostate-specific Antigen. TGF β -mediated repression of T-cell function may include production of IFN γ , which is known to contribute to tumor immunosurveillance.
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T‐cell recognition of a Prostate specific Antigen is not sufficient to induce Prostate tissue destruction
The Prostate, 2006Co-Authors: Jason R. Lees, Bridget Charbonneau, John D. Hayball, Kerrilyn R. Diener, Michael D Brown, Robert J. Matusik, Michael B. Cohen, Timothy L. RatliffAbstract:METHODS The ability of CD8+ T-cells to induce Prostate inflammation was examined using a Prostate ovalbumin expressing transgenic mouse (POET) and/or adoptive transfer of T-cell receptor (TCR) transgenic T-cells (OT-I) that specifically recognize ovalbumin. Localization of inflammatory cells to Prostate tissue was examined following T-cell activation via endogenous prostatic Antigen, recombinant type 5 adenovirus carrying the gene coding ovalbumin (Ad5-mOVA), or adoptive transfer of in vitro Antigen stimulated OT-I cells. RESULTS Ovalbumin specific OT-I cells were activated by autologous Prostate Antigen and trafficked to the Prostate, but did not induce inflammation unless present in overwhelming numbers (∼65% of CD8+ T-cells). Activation of Antigen specific CD8+ T-cells in vitro (peptide pulsed Antigen presenting cells) or in vivo (Ad5-mOVA) induced transitory Prostate inflammation, without induction of Prostate pathology, regardless of CD4+ T-cell availability. Inflammation also was observed in OT-I × POET mice but again, pathological effects were not observed. CONCLUSIONS T lymphocytes specific for a Prostate Antigen are capable of inducing inflammatory infiltration of prostatic tissue rapidly following activation, but do not produce pathological Prostate injury. Prostate 66:578–590, 2006. © 2005 Wiley-Liss, Inc.
