glutamate carboxypeptidase ii

Summary

Summary: A metallocarboxypeptidase that is predominantly expressed as a membrane-bound enzyme. It catalyzes the hydrolysis of an unsubstituted, C-terminal glutamyl residue, typically from PTEROYLPOLYGLUTAMIC ACIDS. It was formerly classified as EC 3.4.19.8.

Top Publications

  1. ncbi Tumor target prostate specific membrane antigen (PSMA) and its regulation in prostate cancer
    Arundhati Ghosh
    George M O Brien Center for Urology Research, Department of Cancer Biology, Lerner Research Institute, Cleveland, Ohio 44195, USA
    J Cell Biochem 91:528-39. 2004
  2. ncbi Expression of the prostate-specific membrane antigen
    R S Israeli
    Urologic Oncology Research Laboratory, Memorial Sloan Kettering Cancer Center, New York, New York 10021
    Cancer Res 54:1807-11. 1994
  3. pmc Glutamate carboxypeptidase II in diagnosis and treatment of neurologic disorders and prostate cancer
    C Barinka
    Institute of Biotechnology, Academy of Sciences of the Czech Republic, Videnska 1083, 14200 Praha 4, Czech Republic
    Curr Med Chem 19:856-70. 2012
  4. ncbi 68Ga-complex lipophilicity and the targeting property of a urea-based PSMA inhibitor for PET imaging
    Matthias Eder
    Radiopharmaceutical Chemistry, German Cancer Research Center, Heidelberg, Germany
    Bioconjug Chem 23:688-97. 2012
  5. pmc Advances in understanding the peptide neurotransmitter NAAG and appearance of a new member of the NAAG neuropeptide family
    Joseph H Neale
    Department of Biology, Georgetown University, Washington, District of Columbia 20057, USA
    J Neurochem 118:490-8. 2011
  6. ncbi Correlation of primary tumor prostate-specific membrane antigen expression with disease recurrence in prostate cancer
    Jeffrey S Ross
    Departments of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York 12208, USA
    Clin Cancer Res 9:6357-62. 2003
  7. pmc Preclinical evaluation of novel glutamate-urea-lysine analogues that target prostate-specific membrane antigen as molecular imaging pharmaceuticals for prostate cancer
    Shawn M Hillier
    Molecular Insight Pharmaceuticals, Cambridge, Massachusetts, USA
    Cancer Res 69:6932-40. 2009
  8. pmc Co-expression and impact of prostate specific membrane antigen and prostate specific antigen in prostatic pathologies
    Awatef Ben Jemaa
    Unit of Immunology and Microbiology Environmental and Carcinogenesis, Faculty of Sciences of Bizerte, 7021 Zarzouna, University of 7 November at Carthage, Tunisia
    J Exp Clin Cancer Res 29:171. 2010
  9. ncbi Is prostate-specific membrane antigen a multifunctional protein?
    Ayyappan K Rajasekaran
    Dept of Pathology and Laboratory Medicine, David Geffen School of Medicine, Univ of California, Los Angeles, 10833 Le Conte Ave, Rm 13 344, CHS, Los Angeles, CA 90095, USA
    Am J Physiol Cell Physiol 288:C975-81. 2005
  10. ncbi Inhibition of glutamate carboxypeptidase II (NAALADase) protects against dynorphin A-induced ischemic spinal cord injury in rats
    Joseph B Long
    Department of Polytrauma and Resuscitation Research, Division of Military Casualty Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910 7500, USA
    Eur J Pharmacol 508:115-22. 2005

Detail Information

Publications205 found, 100 shown here

  1. ncbi Tumor target prostate specific membrane antigen (PSMA) and its regulation in prostate cancer
    Arundhati Ghosh
    George M O Brien Center for Urology Research, Department of Cancer Biology, Lerner Research Institute, Cleveland, Ohio 44195, USA
    J Cell Biochem 91:528-39. 2004
    ..In this review we have discussed the regulation of PSMA expression within the cells, and significance of its expression in prostate cancer and metastasis...
  2. ncbi Expression of the prostate-specific membrane antigen
    R S Israeli
    Urologic Oncology Research Laboratory, Memorial Sloan Kettering Cancer Center, New York, New York 10021
    Cancer Res 54:1807-11. 1994
    ..LNCaP tumors implanted and grown both orthotopically and s.c. in nude mice abundantly express PSM, providing an excellent in vivo model system to study the regulation and modulation of PSM expression...
  3. pmc Glutamate carboxypeptidase II in diagnosis and treatment of neurologic disorders and prostate cancer
    C Barinka
    Institute of Biotechnology, Academy of Sciences of the Czech Republic, Videnska 1083, 14200 Praha 4, Czech Republic
    Curr Med Chem 19:856-70. 2012
    b>Glutamate carboxypeptidase II (GCPII) is a membrane-bound binuclear zinc metallopeptidase with the highest expression levels found in the nervous and prostatic tissue...
  4. ncbi 68Ga-complex lipophilicity and the targeting property of a urea-based PSMA inhibitor for PET imaging
    Matthias Eder
    Radiopharmaceutical Chemistry, German Cancer Research Center, Heidelberg, Germany
    Bioconjug Chem 23:688-97. 2012
    ..It could be demonstrated that the PET-imaging property of a urea-based PSMA inhibitor could significantly be improved with HBED-CC...
  5. pmc Advances in understanding the peptide neurotransmitter NAAG and appearance of a new member of the NAAG neuropeptide family
    Joseph H Neale
    Department of Biology, Georgetown University, Washington, District of Columbia 20057, USA
    J Neurochem 118:490-8. 2011
    ....
  6. ncbi Correlation of primary tumor prostate-specific membrane antigen expression with disease recurrence in prostate cancer
    Jeffrey S Ross
    Departments of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York 12208, USA
    Clin Cancer Res 9:6357-62. 2003
    ....
  7. pmc Preclinical evaluation of novel glutamate-urea-lysine analogues that target prostate-specific membrane antigen as molecular imaging pharmaceuticals for prostate cancer
    Shawn M Hillier
    Molecular Insight Pharmaceuticals, Cambridge, Massachusetts, USA
    Cancer Res 69:6932-40. 2009
    ..PSMA-specific radiopharmaceuticals should provide a novel molecular targeting option for the detection and staging of prostate cancer...
  8. pmc Co-expression and impact of prostate specific membrane antigen and prostate specific antigen in prostatic pathologies
    Awatef Ben Jemaa
    Unit of Immunology and Microbiology Environmental and Carcinogenesis, Faculty of Sciences of Bizerte, 7021 Zarzouna, University of 7 November at Carthage, Tunisia
    J Exp Clin Cancer Res 29:171. 2010
    ....
  9. ncbi Is prostate-specific membrane antigen a multifunctional protein?
    Ayyappan K Rajasekaran
    Dept of Pathology and Laboratory Medicine, David Geffen School of Medicine, Univ of California, Los Angeles, 10833 Le Conte Ave, Rm 13 344, CHS, Los Angeles, CA 90095, USA
    Am J Physiol Cell Physiol 288:C975-81. 2005
    ..Insights into the possible functions of PSMA should improve the diagnostic and therapeutic values of this clinically important molecule...
  10. ncbi Inhibition of glutamate carboxypeptidase II (NAALADase) protects against dynorphin A-induced ischemic spinal cord injury in rats
    Joseph B Long
    Department of Polytrauma and Resuscitation Research, Division of Military Casualty Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910 7500, USA
    Eur J Pharmacol 508:115-22. 2005
    ..These results indicate that 2-PMPA provides effective protection against excitotoxic spinal cord injury...
  11. ncbi NAAG peptidase inhibitor reduces acute neuronal degeneration and astrocyte damage following lateral fluid percussion TBI in rats
    Chunlong Zhong
    Department of Neurological Surgery, The Center for Neuroscience, University of California at Davis, Davis, California 95616 8797, USA
    J Neurotrauma 22:266-76. 2005
    ..05). We conclude that the NAAG peptidase inhibitor ZJ-43 is a potential novel strategy to reduce both neuronal and astrocyte damage associated with the glutamate excitotoxicity after TBI...
  12. pmc Localization of NAAG-related gene expression deficits to the anterior hippocampus in schizophrenia
    Subroto Ghose
    University of Texas Southwestern Medical Center, Dallas, TX 75390 9127, USA
    Schizophr Res 111:131-7. 2009
    ..b>Glutamate carboxypeptidase II (GCPII), an enzyme that metabolizes NAAG, is also implicated in this illness...
  13. pmc Endogenous N-acetylaspartylglutamate (NAAG) inhibits synaptic plasticity/transmission in the amygdala in a mouse inflammatory pain model
    Mary O Adedoyin
    Department of Biology, Georgetown University, Biology Reiss Building 37th and O St NW, Washington, D C 20057, USA
    Mol Pain 6:60. 2010
    ..Evoked excitatory postsynaptic currents (eEPSCs) were studied in neurons in the CeLC of mouse brain slices following stimulation of the spinoparabrachial amygdaloid afferents...
  14. ncbi Docetaxel down-regulates the expression of androgen receptor and prostate-specific antigen but not prostate-specific membrane antigen in prostate cancer cell lines: implications for PSA surrogacy
    Kenji Kuroda
    Laboratory of Urological Oncology, Department of Urology, Weill Cornell Medical College, New York, New York 10065, USA
    Prostate 69:1579-85. 2009
    ..As controls, we also looked at the expression of androgen receptor (AR) and prostate-specific antigen (PSA)...
  15. ncbi Nanoparticle-aptamer bioconjugates: a new approach for targeting prostate cancer cells
    Omid C Farokhzad
    Department of Anesthesiology, Brigham and Women s Hospital, Boston, Massachusetts, USA
    Cancer Res 64:7668-72. 2004
    ..To our knowledge, this represents the first report of targeted drug delivery with nanoparticle-aptamer bioconjugates...
  16. ncbi A series of halogenated heterodimeric inhibitors of prostate specific membrane antigen (PSMA) as radiolabeled probes for targeting prostate cancer
    K P Maresca
    Molecular Insight Pharmaceuticals, Inc, 160 Second Street, Cambridge, Massachusetts 02142, USA
    J Med Chem 52:347-57. 2009
    ....
  17. pmc Noninvasive measurement of androgen receptor signaling with a positron-emitting radiopharmaceutical that targets prostate-specific membrane antigen
    Michael J Evans
    Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Proc Natl Acad Sci U S A 108:9578-82. 2011
    ....
  18. pmc Glutamate carboxypeptidase II inhibition protects motor neurons from death in familial amyotrophic lateral sclerosis models
    Ghanashyam D Ghadge
    Department of Neurology, University of Chicago School of Medicine, Chicago, IL 60637, USA
    Proc Natl Acad Sci U S A 100:9554-9. 2003
    ..this study, we tested whether a neuroprotective strategy involving potent and selective inhibitors of glutamate carboxypeptidase II (GCPII), which converts the abundant neuropeptide N-acetylaspartylglutamate to glutamate, could ..
  19. pmc Characterization of a targeted nanoparticle functionalized with a urea-based inhibitor of prostate-specific membrane antigen (PSMA)
    Sachin S Chandran
    The Department of Chemical and Biomolecular Engineering, The Johns Hopkins University Whiting School of Engineering, Baltimore, Maryland 21231, USA
    Cancer Biol Ther 7:974-82. 2008
    ..Ongoing in vivo studies address the localization, activity and toxicity of these targeted nanoparticles against PSMA-producing human prostate tumor xenografts...
  20. pmc The central nervous system effects, pharmacokinetics and safety of the NAALADase-inhibitor GPI 5693
    J P van der Post
    Centre for Human Drug Research, Leiden, The Netherlands
    Br J Clin Pharmacol 60:128-36. 2005
    ..The aim was to assess the central nervous system (CNS) effects, pharmacokinetics and safety of GPI 5693, an inhibitor of a novel CNS-drug target, NAALADase which is being evaluated for the treatment of neuropathic pain...
  21. ncbi The preventive and therapeutic effects of GCPII (NAALADase) inhibition on painful and sensory diabetic neuropathy
    W Zhang
    Department of Pathology, Wayne State University, Detroit, MI 48201, USA
    J Neurol Sci 247:217-23. 2006
    ..One source is derived from the hydrolysis of the neuropeptide N-acetyl aspartyl glutamate (NAAG) by glutamate carboxypeptidase II (GCPII, also known as NAALADase)...
  22. ncbi Deletion of the glutamate carboxypeptidase II gene in mice reveals a second enzyme activity that hydrolyzes N-acetylaspartylglutamate
    Dean J Bacich
    Department of Cancer Biology, The Cleveland Clinic, Cleveland, Ohio, USA
    J Neurochem 83:20-9. 2002
    b>Glutamate carboxypeptidase II (GCPII, EC 3.14.17.21) is a membrane-bound enzyme found on the extracellular face ofglia. The gene for this enzyme is designated FOLH1 in humans and Folh1 in mice...
  23. pmc Radiohalogenated prostate-specific membrane antigen (PSMA)-based ureas as imaging agents for prostate cancer
    Ying Chen
    Russell H Morgan Department of Radiology and Radiological Sciences, Johns Hopkins Medical Institutions, Baltimore, Maryland 21231, USA
    J Med Chem 51:7933-43. 2008
    ..Because of the many radiohalogenated moieties that can be attached via the epsilon amino group, the intermediate Lys-C(O)-Glu is an attractive template upon which to develop new imaging agents for prostate cancer...
  24. pmc Synthesis and evaluation of technetium-99m- and rhenium-labeled inhibitors of the prostate-specific membrane antigen (PSMA)
    Sangeeta R Banerjee
    Russell H Morgan Department of Radiology and Radiological Sciences, Johns Hopkins Medical Institutions, Baltimore, Maryland 21231, USA
    J Med Chem 51:4504-17. 2008
    ..PSMA can accommodate the steric requirements of (99m)Tc/Re complexes within PSMA inhibitors, the best results achieved with a linker moiety between the epsilon amine of the urea lysine and the chelator...
  25. ncbi The proinflammatory cytokine, IL-6, and its interference with bFGF signaling and PSMA in prostate cancer cells
    Awatef Ben Jemaa
    Unit of Immunology and Microbiology Environmental and Carcinogenesis IMEC, Faculty of Sciences of Bizerte, University of Carthage, 7021 Bizerte, Zarzouna, Tunisia
    Inflammation 36:643-50. 2013
    ..In developing novel therapeutic modalities targeting IL-6, significant attention should be given to PSMA and its inactivation to fight against prostate cancer...
  26. pmc Structure of glutamate carboxypeptidase II, a drug target in neuronal damage and prostate cancer
    Jeroen R Mesters
    Institute of Biochemistry, Center for Structural and Cell Biology in Medicine, University of Lubeck, Lubeck, Germany
    EMBO J 25:1375-84. 2006
    Membrane-bound glutamate carboxypeptidase II (GCPII) is a zinc metalloenzyme that catalyzes the hydrolysis of the neurotransmitter N-acetyl-L-aspartyl-L-glutamate (NAAG) to N-acetyl-L-aspartate and L-glutamate (which is itself a ..
  27. ncbi 2-MPPA, a selective glutamate carboxypeptidase II inhibitor, attenuates morphine tolerance but not dependence in C57/Bl mice
    Ewa Kozela
    Department of Biochemistry, Laboratory of Behavioral Neuroscience, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31 343 Krakow, Poland
    Psychopharmacology (Berl) 183:275-84. 2005
    ..In the present study, we investigated in more detail the effects of GCP II inhibition on opioid dependence and tolerance to its antinociceptive effect in C57/Bl mice using a novel GCP II inhibitor...
  28. pmc Efficient and versatile one-step affinity purification of in vivo biotinylated proteins: expression, characterization and structure analysis of recombinant human glutamate carboxypeptidase II
    J Tykvart
    Gilead Sciences and IOCB Research Centre, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo n 2, Prague 6, Czech Republic
    Protein Expr Purif 82:106-15. 2012
    ..We optimized a protocol for large-scale expression and purification of AviTEV-tagged recombinant human glutamate carboxypeptidase II (Avi-GCPII) with milligram yields per liter of culture...
  29. pmc Pharmacokinetics and pharmacodynamics of the glutamate carboxypeptidase II inhibitor 2-MPPA show prolonged alleviation of neuropathic pain through an indirect mechanism
    James J Vornov
    Brain Science Institute, NeuroTranslational Drug Discovery Program, Johns Hopkins University, Baltimore, Maryland 21205, USA
    J Pharmacol Exp Ther 346:406-13. 2013
    b>Glutamate carboxypeptidase II (GCP II) is a therapeutic target in neurologic disorders associated with excessive activation of glutamatergic systems...
  30. ncbi The role of glutamate signaling in pain processes and its regulation by GCP II inhibition
    K M Wozniak
    Brain Science Institute NeuroTranslational Drug Discovery Program, Johns Hopkins School of Medicine, 855 North Wolfe Street, Baltimore, MD 21205, USA
    Curr Med Chem 19:1323-34. 2012
    ..GCPII (glutamate carboxypeptidase II) cleaves the prevalent neuropeptide NAAG into NAA and glutamate and there is widespread evidence and ..
  31. ncbi Structural optimization of thiol-based inhibitors of glutamate carboxypeptidase II by modification of the P1' side chain
    Pavel Majer
    MGI Pharma, Inc, 6611 Tributary Street, Baltimore, Maryland 21224, USA
    J Med Chem 49:2876-85. 2006
    ..a benzyl moiety at the P1' position have been synthesized and tested for their abilities to inhibit glutamate carboxypeptidase II (GCP II)...
  32. ncbi Heterogeneity of prostate-specific membrane antigen (PSMA) expression in prostate carcinoma with distant metastasis
    Sebastian Mannweiler
    Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036 Graz, Austria
    Pathol Oncol Res 15:167-72. 2009
    ..Our findings clearly support the feasibility but also direct to potential failures of PSMA-targeted in vivo diagnostic and therapeutic approaches in prostate cancer patients with distant metastasis...
  33. ncbi Synthesis and biological evaluation of thiol-based inhibitors of glutamate carboxypeptidase II: discovery of an orally active GCP II inhibitor
    Pavel Majer
    Guilford Pharmaceuticals Inc, 6611 Tributary Street, Baltimore, Maryland 21224, USA
    J Med Chem 46:1989-96. 2003
    A series of 2-(thioalkyl)pentanedioic acids were synthesized and evaluated as inhibitors of glutamate carboxypeptidase II (GCP II, EC 3.4.17.21)...
  34. ncbi Prostate-specific membrane antigen (PSMA) protein expression in normal and neoplastic tissues and its sensitivity and specificity in prostate adenocarcinoma: an immunohistochemical study using mutiple tumour tissue microarray technique
    P Mhawech-Fauceglia
    Department of Pathology and Laboratory Medicine at Roswell Park Cancer Institute, Buffalo, NY 14263, USA
    Histopathology 50:472-83. 2007
    ..To determine prostate-specific membrane antigen (PSMA) expression in normal tissues and in 3161 benign and malignant tumours and subsequently to define its sensitivity and specificity in prostatic adenocarcinoma (PaC)...
  35. ncbi Vascular targeted therapy with anti-prostate-specific membrane antigen monoclonal antibody J591 in advanced solid tumors
    Matthew I Milowsky
    Division of Hematology and Medical Oncology, Department of Medicine, Weill Medical College of Cornell University, New York 10021, USA
    J Clin Oncol 25:540-7. 2007
    ..This was a proof-of-principle evaluation of PSMA as a potential neovascular target. The primary end points were targeting,toxicity, maximum-tolerated dose, pharmacokinetics (PK), and human antihuman antibody (HAHA) response...
  36. pmc Phencyclidine and dizocilpine induced behaviors reduced by N-acetylaspartylglutamate peptidase inhibition via metabotropic glutamate receptors
    Rafal T Olszewski
    Department of Biology, Georgetown University, Washington D C 20057, USA
    Biol Psychiatry 63:86-91. 2008
    ..We previously reported that ZJ43, a potent inhibitor of the enzymes that inactivate synaptically released NAAG, reduced motor and stereotypic effects of PCP in the rat...
  37. ncbi Selective inhibition of NAALADase, which converts NAAG to glutamate, reduces ischemic brain injury
    B S Slusher
    Guilford Pharmaceuticals, Department of Research, Baltimore, Maryland 21224, USA
    Nat Med 5:1396-402. 1999
    ..Both effects could contribute to neuroprotection. These data indicate that NAALADase inhibition may have use in neurological disorders in which excessive excitatory amino acid transmission is pathogenic...
  38. pmc Substrate specificity of prostate-specific membrane antigen
    Marc O Anderson
    Department of Chemistry and Biochemistry, San Francisco State University, San Francisco, CA 94132, USA
    Bioorg Med Chem 15:6678-86. 2007
    ..Lastly, binding modes of endogenous substrates and our best synthetic substrate (4-phenylazobenzoyl-Glu-gamma-Glu) were proposed by computational docking studies into an X-ray crystal structure of the PSMA extracellular domain...
  39. ncbi Recognition of prostate tumor cells by cytotoxic T lymphocytes specific for prostate-specific membrane antigen
    Jun Lu
    Department of Immunology, Mayo Graduate School, and Mayo Cancer Center, Mayo Clinic, Rochester, Minnesota 55905, USA
    Cancer Res 62:5807-12. 2002
    ..These results underline the importance of demonstrating antitumor reactivity of peptide-induced CTLs for the selection of epitopes destined to become immunotherapeutic for prostate cancer...
  40. ncbi Cell-Surface labeling and internalization by a fluorescent inhibitor of prostate-specific membrane antigen
    Tiancheng Liu
    Department of Chemistry, Washington State University, Pullman, Washington, USA
    Prostate 68:955-64. 2008
    ..A novel fluorescent inhibitor was prepared as a model to examine these processes...
  41. pmc Identification of the N-glycosylation sites on glutamate carboxypeptidase II necessary for proteolytic activity
    Cyril Barinka
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo n 2, 166 10 Praha 6, Czech Republic
    Protein Sci 13:1627-35. 2004
    b>Glutamate carboxypeptidase II (GCPII) is a membrane peptidase expressed in the prostate, central and peripheral nervous system, kidney, small intestine, and tumor-associated neovasculature...
  42. pmc The molecular pruning of a phosphoramidate peptidomimetic inhibitor of prostate-specific membrane antigen
    Lisa Y Wu
    Department of Chemistry and Biochemistry, San Francisco State University, 1600 Holloway Avenue, San Francisco, CA 94132, USA
    Bioorg Med Chem 15:7434-43. 2007
    ..86 nM to 4.1 microM. Computational docking, utilizing a recently solved X-ray crystal structure of the recombinant protein, along with enzyme inhibition data, was used to propose a pharmacophore model for the PSMA active site...
  43. ncbi DNA fusion gene vaccines induce cytotoxic T-cell attack on naturally processed peptides of human prostate-specific membrane antigen
    Gisella E Vittes
    University of Southampton School of Medicine, Southampton General Hospital, Southampton, UK
    Eur J Immunol 41:2447-56. 2011
    ..The preclinical model provides a powerful tool for generating CD8(+) T cells able to predict whether target cells can process and present peptides, essential for planning peptide vaccine-based clinical trials...
  44. ncbi Probing for a hydrophobic a binding register in prostate-specific membrane antigen with phenylalkylphosphonamidates
    Jack Maung
    Department of Chemistry and Biochemistry, San Francisco State University, 1600 Holloway Ave, San Francisco, CA 94132, USA
    Bioorg Med Chem 12:4969-79. 2004
    ....
  45. ncbi Prostate-specific membrane antigen expression is a potential prognostic marker in endometrial adenocarcinoma
    Paulette Mhawech-Fauceglia
    Department of Pathology, Roswell Park Cancer Institute, Elm and Carlton Street, Buffalo, NY 14263, USA
    Cancer Epidemiol Biomarkers Prev 17:571-7. 2008
    ....
  46. ncbi Orally active glutamate carboxypeptidase II inhibitor 2-MPPA attenuates dizocilpine-induced prepulse inhibition deficits in mice
    Yuto Takatsu
    Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260 8670, Japan
    Brain Res 1371:82-6. 2011
    b>Glutamate carboxypeptidase II (GCP II) is a glial enzyme responsible for the hydrolysis of N-acetylaspartylglutamate (NAAG) into glutamate and N-acetylaspartate (NAA)...
  47. ncbi 123I-MIP-1072, a small-molecule inhibitor of prostate-specific membrane antigen, is effective at monitoring tumor response to taxane therapy
    Shawn M Hillier
    Molecular Insight Pharmaceuticals, Cambridge, Massachusetts 02142, USA
    J Nucl Med 52:1087-93. 2011
    ....
  48. ncbi Bioanalysis of N-acetyl-aspartyl-glutamate as a marker of glutamate carboxypeptidase II inhibition
    Ajit G Thomas
    Brain Science Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Anal Biochem 404:94-6. 2010
    ..based on differences between glutamate concentrations before and after NAAG hydrolysis with exogenous glutamate carboxypeptidase II (GCP II) using high-performance liquid chromatography (HPLC) followed by fluorescence detection...
  49. ncbi Aspartoacylase deficiency does not affect N-acetylaspartylglutamate level or glutamate carboxypeptidase II activity in the knockout mouse brain
    Sankar Surendran
    Department of Pediatrics, Childrens Hospital, The University of Texas Medical Branch, Rm 3 350, Galveston, TX 77555 0359, USA
    Brain Res 1016:268-71. 2004
    ..The NAAG hydrolyzing enzyme, glutamate carboxypeptidase II (GCP II), activity was normal in the knockout mouse brain...
  50. ncbi Antinociceptive effects of N-acetylaspartylglutamate (NAAG) peptidase inhibitors ZJ-11, ZJ-17 and ZJ-43 in the rat formalin test and in the rat neuropathic pain model
    Tatsuo Yamamoto
    Department of Anaesthesiology, Graduate School of Medicine, Chiba University, 1 8 1 Inohana, Chuo Ku, Chiba shi, Chiba 260 8670, Japan
    Eur J Neurosci 20:483-94. 2004
    ..In contrast, peptidase inhibition did not affect the threshold for withdrawal from a noxious mechanical stimulus or from an acute thermal stimulus in the hotplate test...
  51. ncbi Spinal N-acetyl-alpha-linked acidic dipeptidase (NAALADase) inhibition attenuates mechanical allodynia induced by paw carrageenan injection in the rat
    T Yamamoto
    Department of Anesthesiology, School of Medicine, Chiba University, 1 8 1 Inohana, Chuo Ku, Chiba shi, 260 0856, Chiba, Japan
    Brain Res 909:138-44. 2001
    ..These data suggested that the inhibition of spinal NAALADase alleviated mechanical allodynia induced by paw carrageenan injection...
  52. ncbi Radiolabeled small-molecule ligands for prostate-specific membrane antigen: in vivo imaging in experimental models of prostate cancer
    Catherine A Foss
    Johns Hopkins University, Baltimore, Maryland 21287 2182, USA
    Clin Cancer Res 11:4022-8. 2005
    ..Our goal in this study was to develop a series of PSMA-based imaging agents for clinical use...
  53. ncbi Local administration of N-acetylaspartylglutamate (NAAG) peptidase inhibitors is analgesic in peripheral pain in rats
    Tatsuo Yamamoto
    Department of Anaesthesiology, Graduate School of Medicine, Chiba University, 1 8 1 Inohana, Chuo Ku, Chiba shi, Chiba 260 8670, Japan
    Eur J Neurosci 25:147-58. 2007
    ....
  54. ncbi A changing world for DCvax: a PSMA loaded autologous dendritic cell vaccine for prostate cancer
    Mayer Fishman
    Moffitt Cancer Center, Department of Genitourinary Oncology, Tampa, FL 33612, USA
    Expert Opin Biol Ther 9:1565-75. 2009
    ..More recently DCvax brain, a product using a similar DC platform showed encouraging Phase I-II results and sipleucel-T, a prostatic acid phosphatase (PAP)-directed DC immunotherapy had positive Phase III results...
  55. pmc Group II mGluR agonist LY354740 and NAAG peptidase inhibitor effects on prepulse inhibition in PCP and D-amphetamine models of schizophrenia
    Caterina P Profaci
    Department of Biology, Georgetown University, 37th and O Sts, NW, Washington, DC 20057, USA
    Psychopharmacology (Berl) 216:235-43. 2011
    ....
  56. ncbi Targeting metastatic prostate cancer with radiolabeled monoclonal antibody J591 to the extracellular domain of prostate specific membrane antigen
    Neil H Bander
    Department of Urology, Division of Nuclear Medicine, New York Presbyterian Hospital Weill Medical College of Cornell University, 525 East 68th Street, Starr 900, New York, NY 10021, USA
    J Urol 170:1717-21. 2003
    ....
  57. ncbi Novel prostate-specific promoter derived from PSA and PSMA enhancers
    Sang Jin Lee
    Department of Urology, Indiana University, Indianapolis, Indiana 46202, USA
    Mol Ther 6:415-21. 2002
    ..Our results demonstrated the potential use of PSES for the treatment of androgen-independent prostate cancer patients...
  58. ncbi NAAG peptidase inhibitors and their potential for diagnosis and therapy
    Jia Zhou
    Acenta Discovery, Inc, 9030 South Rita Road, Suite 300, Tucson, Arizona 85747, USA
    Nat Rev Drug Discov 4:1015-26. 2005
    ....
  59. ncbi NAAG peptidase inhibitor increases dialysate NAAG and reduces glutamate, aspartate and GABA levels in the dorsal hippocampus following fluid percussion injury in the rat
    Chunlong Zhong
    Department of Neurological Surgery, University of California at Davis, Davis, California 95616 8797, USA
    J Neurochem 97:1015-25. 2006
    ..The results are consistent with the hypothesis that inhibition of NAAG peptidase may reduce excitotoxic events associated with TBI...
  60. ncbi Identification and characterization of nuclease-stabilized RNA molecules that bind human prostate cancer cells via the prostate-specific membrane antigen
    Shawn E Lupold
    Department of Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287 2101, USA
    Cancer Res 62:4029-33. 2002
    ..These aptamers may be used clinically as NAALADase inhibitors or be modified to carry imaging agents and therapeutic agents directed to prostate cancer cells...
  61. ncbi Dendritic cell-based multi-epitope immunotherapy of hormone-refractory prostate carcinoma
    Ying Waeckerle-Men
    Research Department, Cantonal Hospital St Gallen, 9007, St Gallen, Switzerland
    Cancer Immunol Immunother 55:1524-33. 2006
    ..In this trial, we determined the immunostimulatory capacity of autologous DC pulsed with multiple T cell epitopes derived from four different prostate-specific antigens in patients with advanced hormone-refractory prostate cancer...
  62. ncbi DNA vaccination with electroporation induces increased antibody responses in patients with prostate cancer
    Lindsey Low
    Cancer Sciences Division, University of Southampton, Southampton SO16 6YD, UK
    Hum Gene Ther 20:1269-78. 2009
    ..Responses persisted to 18 months of follow-up. These data establish EP as a potent method for stimulating humoral responses induced by DNA vaccination in humans...
  63. pmc Systemic administration of optimized aptamer-siRNA chimeras promotes regression of PSMA-expressing tumors
    Justin P Dassie
    Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA
    Nat Biotechnol 27:839-49. 2009
    ..Anti-tumor activity was further enhanced by appending a polyethylene glycol moiety, which increased the chimeras' circulating half-life...
  64. ncbi Evaluation of genetic variants in the reduced folate carrier and in glutamate carboxypeptidase II for spina bifida risk
    Isabelle Morin
    Departments of Pediatrics and Human Genetics, McGill University, Montreal Children s Hospital Research Institute, 4060 Ste Catherine West, Room 200, Montreal, Canada H3Z 2Z3
    Mol Genet Metab 79:197-200. 2003
    ..Two recently identified variants are the 1561C-->T (H475Y) mutation in glutamate carboxypeptidase II (GCPII) and the 80A-->G (H27R) change in the reduced folate carrier RFC-1...
  65. ncbi Gene therapy for prostate cancer by controlling adenovirus E1a and E4 gene expression with PSES enhancer
    Xiong Li
    Departments of Urology, Microbiology and Immunology, Radiology, Medicine, and Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana
    Cancer Res 65:1941-51. 2005
    ..These data show that adenoviral replication can be tightly controlled in a novel fashion by controlling adenoviral E1a and E4 genes simultaneously with a single enhancer...
  66. ncbi NFATc1 with AP-3 site binding specificity mediates gene expression of prostate-specific-membrane-antigen
    Sang Jin Lee
    Department of Urology, Indiana University, Indianapolis, IN 46202, USA
    J Mol Biol 330:749-60. 2003
    ..Furthermore, ionomycin (calcium ionophore) and TPA augmented the enhancer activity of PSME, implying that calcium is an important regulator for PSMA expression in prostate cancer cell...
  67. pmc The homodimer of prostate-specific membrane antigen is a functional target for cancer therapy
    NORBERT SCHULKE
    Progenics Pharmaceuticals, Inc, and PSMA Development Company, LLC, Tarrytown, NY 10591, USA
    Proc Natl Acad Sci U S A 100:12590-5. 2003
    ..These findings on PSMA structure and biology may have important implications for active and passive immunotherapy of prostate and other cancers...
  68. pmc Multivalent scaffolds for affinity maturation of small molecule cell surface binders and their application to prostate tumor targeting
    Valerie Humblet
    Institute of Organic Chemistry, Justus Liebig Universitat Giessen, Heinrich Buff Ring 58, 35390 Giessen, Germany
    J Med Chem 52:544-50. 2009
    ....
  69. ncbi Molecular evolution of the transferrin receptor/glutamate carboxypeptidase II family
    Lisa Ann Lambert
    Department of Biology, Chatham College, Woodland Road, Pittsburgh, PA 15232, USA
    J Mol Evol 64:113-28. 2007
    ..Other family members include transferrin receptor 2 (TfR2), glutamate carboxypeptidase II (GCP2 or PSMA), N-acetylated alpha-linked acidic dipeptidase-like protein (NLDL), N-acetylated alpha-..
  70. ncbi Design of NAALADase inhibitors: a novel neuroprotective strategy
    P F Jackson
    Guilford Pharmaceuticals Inc, 6611 Tributary Street, Baltimore, MD 21224, USA
    Curr Med Chem 8:949-57. 2001
    ..As such, NAALADase inhibition represents a novel method of regulating extracellular glutamate levels and provides a new avenue for the treatment of neurological disorders...
  71. ncbi Prostate-specific membrane antigen: a novel folate hydrolase in human prostatic carcinoma cells
    J T Pinto
    Nutrition Research Laboratory, Urology Research Laboratory, Pharmacology Analytical Laboratory, and George M O Brien Urology Research Center, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Clin Cancer Res 2:1445-51. 1996
    ..Those developing future therapeutic strategies in the treatment of prostate cancer that utilize folate antagonists need to consider this mechanism of resistance...
  72. ncbi Mice lacking glutamate carboxypeptidase II are protected from peripheral neuropathy and ischemic brain injury
    Dean J Bacich
    Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
    J Neurochem 95:314-23. 2005
    ..A new strategy for the treatment of neuronal injury involves inhibition of the neuropeptidase glutamate carboxypeptidase II (GCP II), also known as N-acetylated alpha-linked acidic dipeptidase...
  73. ncbi Effect of carbohydrate moieties on the folate hydrolysis activity of the prostate specific membrane antigen
    Arundhati Ghosh
    George O Brien Center for Urology Research, Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA
    Prostate 57:140-51. 2003
    ....
  74. ncbi Amino acids at the N- and C-termini of human glutamate carboxypeptidase II are required for enzymatic activity and proper folding
    Cyril Barinka
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, The Czech Republic
    Eur J Biochem 271:2782-90. 2004
    Human glutamate carboxypeptidase II (GCPII) is a co-catalytic metallopeptidase and its putative catalytic domain is homologous to the aminopeptidases from Vibrio proteolyticus and Streptomyces griseus...
  75. pmc Isolation and expression of a rat brain cDNA encoding glutamate carboxypeptidase II
    R Luthi-Carter
    Department of Psychiatry, Massachusetts General Hospital East, Charlestown, MA 02129, USA
    Proc Natl Acad Sci U S A 95:3215-20. 1998
    ....
  76. ncbi The neurotransmitter N-acetylaspartylglutamate in models of pain, ALS, diabetic neuropathy, CNS injury and schizophrenia
    Joseph H Neale
    Department of Biology, Georgetown University, Washington DC 20007 1229, USA
    Trends Pharmacol Sci 26:477-84. 2005
    ..In this review, we summarize recent studies in these animal models and discuss the mechanisms by which NAAG peptidase inhibitors achieve these effects...
  77. pmc Dysregulation of glutamate carboxypeptidase II in psychiatric disease
    Tomas R Guilarte
    Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
    Schizophr Res 99:324-32. 2008
    Experimental evidence is beginning to converge on an important role for dysregulation of glutamate carboxypeptidase II (GCPII) in schizophrenia...
  78. ncbi Influence of a glutamate carboxypeptidase II (GCPII) polymorphism (1561C-->T) on plasma homocysteine, folate and vitamin B(12) levels and its relationship to cardiovascular disease risk
    Karin J A Lievers
    Department of Pediatrics, PO Box 9101, University Medical Center Nijmegen, 6500 HB, Nijmegen, The Netherlands
    Atherosclerosis 164:269-73. 2002
    ..An impairment of folate distribution can be an important cause of hyperhomocysteinemia. Glutamate carboxypeptidase II (GCPII) regulates the absorption of dietary folates...
  79. pmc Intracerebroventricular administration of N-acetylaspartylglutamate (NAAG) peptidase inhibitors is analgesic in inflammatory pain
    Tatsuo Yamamoto
    Department of Biology, Georgetown University, Washington, DC 20057, USA
    Mol Pain 4:31. 2008
    ..Consistent with NAAG's activation of group II metabotropic glutamate receptors, this analgesia is blocked by a group II antagonist...
  80. ncbi Prostate-specific membrane antigen (PSMA) enzyme activity is elevated in prostate cancer cells
    R G Lapidus
    Guilford Pharmaceuticals, Inc, Baltimore, Maryland 21224, USA
    Prostate 45:350-4. 2000
    ..The prostate enzyme has activity in both the membrane and cytosolic fractions termed PSMA and PSMA', respectively...
  81. ncbi Inhibition of spinal N-acetylated-alpha-linked acidic dipeptidase produces an antinociceptive effect in the rat formalin test
    T Yamamoto
    Department of Anesthesiology, School of Medicine, Chiba University, 1 8 1 Inohana, Chuo Ku, Chiba shi, 260 8670, Chiba, Japan
    Neuroscience 102:473-9. 2001
    ....
  82. ncbi Molecular cloning of a peptidase against N-acetylaspartylglutamate from a rat hippocampal cDNA library
    T Bzdega
    Department of Biology, Georgetown University, Washington, D C 20057 1229, U S A
    J Neurochem 69:2270-7. 1997
    ..Spinal cord yielded an amplification product only with primers for the 5' end of the hippocampal cDNA...
  83. ncbi Expression of prostate-specific membrane antigen (PSMA), increases cell folate uptake and proliferation and suggests a novel role for PSMA in the uptake of the non-polyglutamated folate, folic acid
    Veronica Yao
    Department of Urology, University of Pittsburgh, Pittsburgh, PA 15232, USA
    Prostate 70:305-16. 2010
    ....
  84. pmc Prostate-specific membrane antigen is a hydrolase with substrate and pharmacologic characteristics of a neuropeptidase
    R E Carter
    Department of Psychiatry, Massachusetts General Hospital East, Charlestown 02129, USA
    Proc Natl Acad Sci U S A 93:749-53. 1996
    ..These results also raise questions about the role of PSM in both normal and pathologic prostate epithelial-cell function...
  85. ncbi Detection of extraprostatic prostate cells utilizing reverse transcription-polymerase chain reaction
    S L Su
    Northwest Biotherapeutics, Inc, Seattle, Washington 98125, USA
    Semin Surg Oncol 18:17-28. 2000
    ..Data from PSA- or PSMA-RT-PCR using lymph nodes as the tissue source is more encouraging. RT-PCR was able to detect PSA and/or PSMA positive samples that have not been detected by conventional pathology...
  86. ncbi Detection and characterization of the prostate-specific membrane antigen (PSMA) in tissue extracts and body fluids
    J K Troyer
    Department of Microbiology and Immunology, Eastern Virginia Medical School, Norfolk 23501, USA
    Int J Cancer 62:552-8. 1995
    ..Second generation antibodies generated against different epitopes may be required to determine if PSMA is shed into serum. Our results support the hypothesis that PSMA is a novel prostate biomarker...
  87. ncbi High expression of PSM-E correlated with tumor grade in prostate cancer: a new alternatively spliced variant of prostate-specific membrane antigen
    Kai yuan Cao
    Research Centre for Clinical Laboratory Standard, Zhongshan School of Medicine, Sun Yat Sen University, Guangdong, China
    Prostate 67:1791-800. 2007
    ..In the current study, PSMA cDNA was cloned from PCa tissue by RT-PCR. After sequencing, a new spliced variant of PSMA (PSM-E) was discovered and its specificity in PCa was evaluated...
  88. ncbi NAAG peptidase inhibition reduces locomotor activity and some stereotypes in the PCP model of schizophrenia via group II mGluR
    Rafal T Olszewski
    Department of Biology, Georgetown University, Washington, DC, USA
    J Neurochem 89:876-85. 2004
    ..This novel compound is a potent inhibitor of enzymes, glutamate carboxypeptidase II (K(i) = 0.8 nM) and III (K(i) = 23 nM) that deactivate NAAG following synaptic release...
  89. ncbi Progress in the discovery and development of glutamate carboxypeptidase II inhibitors
    Takashi Tsukamoto
    MGI Pharma, Inc, 6611 Tributary Street, Baltimore, MD 21224, USA
    Drug Discov Today 12:767-76. 2007
    ..past 10 years, substantial progress has been made in the discovery and development of small molecule glutamate carboxypeptidase II (GCP II) inhibitors...
  90. ncbi Glutamate carboxypeptidase II inhibition as a novel therapeutic target
    C Rojas
    Guilford Pharmaceuticals Inc, 6611 Tributary Street, Baltimore, Maryland 21224 USA
    Adv Exp Med Biol 524:205-13. 2003
  91. ncbi Expression of prostate specific membrane antigen and three alternatively spliced variants of PSMA in prostate cancer patients
    Thomas D Schmittgen
    Division of Pharmaceutics, Ohio State University, College of Pharmacy, Columbus, OH 43210, USA
    Int J Cancer 107:323-9. 2003
    ..We note increased PSMA expression in some malignant tissues, however, these increases are modest in magnitude. We also report that the expression of a novel splice variant, PSM-D, is elevated in prostate cancer metastases...
  92. pmc Prostate-specific membrane antigen regulates angiogenesis by modulating integrin signal transduction
    Rebecca E Conway
    University of Connecticut Health Center, Center for Vascular Biology MC3501, Department of Cell Biology, Farmington, CT 06030 350l, USA
    Mol Cell Biol 26:5310-24. 2006
    ..Therefore, we have identified a novel role for PSMA as a true molecular interface, integrating both extracellular and intracellular signals during angiogenesis...
  93. ncbi Dissociation between androgen responsiveness for malignant growth vs. expression of prostate specific differentiation markers PSA, hK2, and PSMA in human prostate cancer models
    Samuel R Denmeade
    The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231, USA
    Prostate 54:249-57. 2003
    ..regulation of expression of prostate differentiation specific markers PSA, hK2, and PSMA...
  94. ncbi Regulation of glutamate carboxypeptidase II function in corticolimbic regions of rat brain by phencyclidine, haloperidol, and clozapine
    Cecilia Flores
    Department of Psychiatry, Harvard Medical School and McLean Hospital, Mailman Research Center, Belmont, MA, USA
    Neuropsychopharmacology 28:1227-34. 2003
    ..NAAG is catabolized to glutamate and N-acetyl-aspartate by the astrocytic enzyme glutamate carboxypeptidase II (GCP II)...
  95. ncbi Morphine tolerance and reward but not expression of morphine dependence are inhibited by the selective glutamate carboxypeptidase II (GCP II, NAALADase) inhibitor, 2-PMPA
    Piotr Popik
    Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31 343 Krakow, Poland
    Neuropsychopharmacology 28:457-67. 2003
    Inhibition of glutamate carboxypeptidase II (GCP II; NAALADase) produces a variety of effects on glutamatergic neurotransmission...
  96. ncbi The cloning and characterization of a second brain enzyme with NAAG peptidase activity
    Tomasz Bzdega
    Department of Biology, Georgetown University, Washington, D C, USA
    J Neurochem 89:627-35. 2004
    ..It is speculated that the enzyme, glutamate carboxypeptidase II (GCPII, EC 3.14.17.21), participates in this inactivation...
  97. ncbi Glutamate carboxypeptidase II: a polymorphism associated with lower levels of serum folate and hyperhomocysteinemia
    A M Devlin
    Department of Internal Medicine, University of California, Davis, CA 95616, USA
    Hum Mol Genet 9:2837-44. 2000
    ..These data suggest that the presence of the H475Y GCPII allele impairs the intestinal absorption of dietary folates, resulting in relatively low blood folate levels and consequent hyperhomocysteinemia...
  98. ncbi Glutamate carboxypeptidase II (NAALADase) inhibition as a novel therapeutic strategy
    Ajit G Thomas
    Guilford Pharmaceuticals Inc, 6611 Tributary Street, Baltimore, Maryland 21224, USA
    Adv Exp Med Biol 576:327-37; discussion 361-3. 2006
    ..GCP II inhibition may represent a novel glutamate regulating strategy devoid of the side effects that have hampered the development of postsynaptic glutamate receptor antagonists...
  99. ncbi Prostate-specific membrane antigen association with filamin A modulates its internalization and NAALADase activity
    Gopalakrishnapillai Anilkumar
    Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, USA
    Cancer Res 63:2645-8. 2003
    ..These results suggest that filamin might be an important regulator of PSMA function...
  100. ncbi Hydrolysis of the neuropeptide N-acetylaspartylglutamate (NAAG) by cloned human glutamate carboxypeptidase II
    R Luthi-Carter
    Laboratory of Molecular and Developmental Neuroscience, Massachusetts General Hospital East, Room 2510, Charlestown, MA 02129, USA
    Brain Res 795:341-8. 1998
    b>Glutamate carboxypeptidase II may modulate excitatory neurotransmission through the catabolism of the neuropeptide N-acetylaspartylglutamate (NAAG) and possibly other endogenous peptide substrates...
  101. ncbi Molecular characterization of human brain N-acetylated alpha-linked acidic dipeptidase (NAALADase)
    R Luthi-Carter
    Laboratory of Molecular and Developmental Neuroscience, Massachusetts General Hospital East, Charlestown, Massachusetts, USA
    J Pharmacol Exp Ther 286:1020-5. 1998
    ..Therefore, we conclude that the form of NAALADase also known as PSMA is expressed in brain and comprises a significant fraction of brain NAALADase activity...

Research Grants53

  1. Prodrugs of NAAG Peptidase Inhibitors for the Treatment of Schizophrenia
    Jia Zhou; Fiscal Year: 2009
    ....
  2. GLUTAMATERGIC DYSFUNCTION AND SCHIZOPHRENIA
    Joseph T Coyle; Fiscal Year: 2010
    ..Project 4: Coyle has created mice with conditional knockouts of seririe racemase and glutamate carboxypeptidase II to determine the electrophysiologic and behavioral consequences of suppressing their expression jn ..
  3. GCPII-Based Brain Imaging Agents
    Martin G Pomper; Fiscal Year: 2011
    ..effect on other transmitter systems, we have embarked upon a program to develop imaging agents for glutamate carboxypeptidase II (GCPII), an enzyme within the brain that cleaves Nacetylaspartylglutamate (NAAG), to the glutamatergic ..
  4. GCPII Inihibitors for the treatment of chemotherapy-induced neuropathy
    BARBARA STAUCH SLUSHER; Fiscal Year: 2013
    ..Inhibition of the glial enzyme glutamate carboxypeptidase II (GCPII) has been shown to selectively dampen excessive glutamate transmission and alleviate ..
  5. METABOTROPIC GLU RECEPTORS IN TRAUMATIC BRAIN INJURY
    Bruce Lyeth; Fiscal Year: 2009
    ..This research will also provide clinically relevant information about potential pharmacological agents for the treatment of human head injury. ..
  6. NAAG Peptidase Inhibitors for the Treatment of Traumatic Brain Injury
    Jia Zhou; Fiscal Year: 2009
    ....
  7. MICRODIALYSIS OF NAA/NAAG IN FOCAL EPILEPTOGENESIS
    JOHN SLOPIS; Fiscal Year: 2000
    ....
  8. Fibroblast Activation Protein-alpha Activated Anti-Stromal Prodrug Therpay for Ca
    Samuel R Denmeade; Fiscal Year: 2010
    ..e. "stroma") within cancers rather than the cancer cells themselves can be effective therapy. The FAP- activated prodrug, therefore, could represent a new targeted therapy for a variety of human cancers. ..
  9. Developing NAAG Peptidase Inhibitors for Neuroprotection
    JOSEPH NEALE; Fiscal Year: 2005
    ..been synthesized and tested for their ability to inhibit enzymes that hydrolyze NAAG, particularly glutamate carboxypeptidase II (GCPII)...
  10. SAMe and Folate Deficiency in Alcoholic Mircropigs
    Charles Halsted; Fiscal Year: 2006
    ..While furthering understanding of interactions of methionine metabolites on pathways of liver injury, the project may establish novel approaches to the prevention and treatment of ALD. [unreadable] [unreadable] [unreadable]..
  11. Studies of Human Folate Hydrolase
    Charles Halsted; Fiscal Year: 2005
    ..characterized the molecular properties of human intestinal folate hydrolase, which is an expression of Glutamate Carboxypeptidase II (GCPII)...
  12. NAAG PEPTIDASE AND NEURONAL FUNCTION
    JOSEPH NEALE; Fiscal Year: 2008
    ..The influence of elevated NAAG levels in vivo, obtained by inhibition of NAAG peptidase activity, will be tested in rat brain and spinal cord and in transgenic mice expressing GLT-1-GFP and GLAST-GFP fusion proteins. ..
  13. EFFECTS OF SAM IN PATIENTS WITH ALCOHOLIC LIVER DISEASE
    Charles Halsted; Fiscal Year: 2007
    ..By confirming the relationship of abnormal methionine metabolism to clinical, biochemical, and pathologic disease severity, the study will establish a metabolic basis for determining the efficacy of SAM intervention in ALD. ..
  14. Lentivirus Gene Therapy for Farber Disease in NHPs
    Jeffrey Medin; Fiscal Year: 2007
    ..This proposed study would thus be the first to fully test LV-mediatedcorrection for an LSD in a more clinically relevant model; that of NHPs. ..
  15. PSMA-based Gene Reporter-Probe System(RMI)
    Martin Pomper; Fiscal Year: 2008
    ..unreadable] [unreadable]..
  16. Human PSMA MAb Radioimmunotherapy for Prostate Cancer
    Dangshe Ma; Fiscal Year: 2007
    ..Successin the Phase II project is defined as the introduction of a promising new molecularly targeted therapy into clinical testing for a currently untreatable form of advanced prostate cancer. ..
  17. GCPII-Based Brain Imaging Agents
    Martin Pomper; Fiscal Year: 2008
    ..effect on other transmitter systems, we have embarked upon a program to develop imaging agents for glutamate carboxypeptidase II (GCPII), an enzyme within the brain that cleaves Nacetylaspartylglutamate (NAAG), to the glutamatergic ..
  18. Perinatal infection, cytokines and brain injury
    Zhengwei Cai; Fiscal Year: 2008
    ....
  19. PSMA Antibody-Drug Conjugate for Prostate Cancer Therapy
    Dangshe Ma; Fiscal Year: 2008
    ..Success in the Phase II project is defined as demonstrating favorable preclinical safety and activity profiles to support human testing of a promising molecularly targeted therapy for HRPC. ..
  20. CTLA-4 Inhibition and Autoimmunity in Melanoma
    Jeffrey Weber; Fiscal Year: 2008
    ..abstract_text> ..
  21. Phase I Study of ALT-801 in Metastatic Melanoma/Kidney Cancer Patients
    Mayer Fishman; Fiscal Year: 2009
    ....
  22. Chemistry and Biology of 5-HT2C Receptor Ligands for Drug Abuse
    ALAN PAUL KOZIKOWSKI; Fiscal Year: 2010
    ....
  23. Enhancement of methotrexate uptake in childhood ALL
    John McGuire; Fiscal Year: 2009
    ..If successful, this research could provide a way to increase the effectiveness of methotrexate, a key drug used in treating childhood acute lymphoblastic leukemia, and thus increase the cure rate in this disease. ..
  24. Folate in Schizophrenia
    Donald C Goff; Fiscal Year: 2010
    ..This will be the first adequately-powered study to assess efficacy and identify predictors of response. ..
  25. Dietary Methyl Content, Epigenetics and Breast Cancer
    Jia Chen; Fiscal Year: 2010
    ..To identify the factors that determine the patterns of methylation can provide evidence for the mechanisms of the disease as well as identify at-risk populations in which appropriate diet-based intervention can be provided. ..
  26. Novel Human Anti-CD19 Antibodies for Lymphoma Therapy
    Dangshe Ma; Fiscal Year: 2004
    ..Success in the project would provide strong impetus to rapidly advance the most promising agents into development for human clinical testing. ..
  27. Dendritic Cell Vaccination During Lymphoid Reconstitution
    Jeffrey Weber; Fiscal Year: 2008
    ..Toxicity as well as clinical response will be secondary endpoints. The cohort with the optimal level of immune response will be taken forward in future studies. ..
  28. PSMA-based PET Ligands for Prostate Cancer Imaging
    Martin Pomper; Fiscal Year: 2007
    ..Those probes are based on our initial success in synthesizing inhibitors of glutamate carboxypeptidase II (GCPII, a.k.a...
  29. BIOLOGICAL STUDIES OF PIPERIDINE ANALOGS OF COCAINE
    Alan Kozikowski; Fiscal Year: 2001
    ..4. For compounds meeting set criteria, to further evaluate their behavioral pharmacological profile in animals using intravenous drug self-administration and drug discrimination procedures. ..
  30. SERINE PROTEASES IN PROSTATE CANCER METASTASIS
    Peter Nelson; Fiscal Year: 2002
    ..4) Characterize the role of prostate and TMPRSS2 in prostate cancer bone metastasis using in vitro and in vivo systems. ..
  31. IN VITRO/IN VIVO ACTIVATED DENDRITIC CELLS FOR MELANOMA
    Jeffrey Weber; Fiscal Year: 2003
    ....
  32. HPV DNA VACCINE FOR CERVICAL PRE NEOPLASIA
    Jeffrey Weber; Fiscal Year: 2003
    ..To insure that spontaneous regression does not account for a portion of the responses, baseline measurements will be followed one month later by a second set of assessments prior to the start of the vaccine. ..
  33. IL-12 as an Adjuvant for a Melanoma Peptide Vaccine
    Jeffrey Weber; Fiscal Year: 2003
    ..The results of those assays will be used to design randomized phase III trials for resected high risk melanoma and to develop strategies for overcoming antigen-specific unresponsiveness in melanoma patients. ..
  34. CHEMICAL AND PHARMACOLOGICAL STUDIES OF COCAINE ANALOGS
    Alan Kozikowski; Fiscal Year: 2004
    ....
  35. DESIGN OF LIGANDS SELECTIVE FOR THE DAG SUPERFAMILY
    Alan Kozikowski; Fiscal Year: 2002
    ..To assess the effect of alterations in the ligand's hydrophobic side chain on its tumor promoting activity, studies of skin hyperplasia will be conducted. ..
  36. GENETICS OF PROSTATE CANCER SUSCEPTIBILITY
    Peter Nelson; Fiscal Year: 2005
    ..The resulting data will provide information about the type and distribution of mutations in high-risk families as well as provide useful information for understanding genetic heterogeneity of prostate cancer. ..
  37. Micro RNA Expression and Cancer
    Thomas Schmittgen; Fiscal Year: 2005
    ..Assays developed with this research may help to identify the function of a new class of genes in humans. ..
  38. PSMA-based SPECT Tracers for Prostate Cancer Imaging
    Martin Pomper; Fiscal Year: 2007
    ..Those probes are based on our initial success in synthesizing inhibitors of glutamate carboxypeptidase II (GCPII, a.k.a...
  39. Perinatal hypoxia-ischemia, glutamate receptors, and Nitric Oxide Synthase
    Zhengwei Cai; Fiscal Year: 2007
    ..Direct effects of inflammatory cytokines and IGF-1 on survival and differentiation of OLs will be examined in cultures of OLs at various maturation stages. ..
  40. Imaging Serotonergic Transmission in HIV Depression
    Martin Pomper; Fiscal Year: 2006
    ..abstract_text> ..
  41. Real-time PCR expression profiling of microRNA
    Thomas Schmittgen; Fiscal Year: 2006
    ..The unparallel sensitivity and specificity of real-time PCR as applied to this new and exciting class of regulatory RNAs should propel the field into new directions not only in cancer but in other areas of human health. ..
  42. Androgen Signaling in Neoplastic Prostate Growth
    Peter Nelson; Fiscal Year: 2006
    ..abstract_text> ..
  43. PKC Modulators for the Treatment of Alzheimer's disease
    Alan Kozikowski; Fiscal Year: 2008
    ..For the best compounds from Aim 2, perform studies in triple transgenic mice to ascertain effects on Abeta and sAPPalpha levels and plaque formation in vivo. ..
  44. CNS METABOLIC CORRELATES OF HIV DEMENTIA BY MRS IMAGING
    Martin Pomper; Fiscal Year: 2001
    ..abstract_text> ..
  45. Development of a Urological CD Cell Typing System
    Peter Nelson; Fiscal Year: 2009
    ..These studies will involve the evaluation of in vitro growth characteristics, cellular gene expression, organ topography, inter-species conservation, and transgenic animal models. ..
  46. Radioimmunotherapy for Prostate Cancer
    Michael Morris; Fiscal Year: 2007
    ..The acquisition of these skills combined with the completion of the research plan will allow the candidate to pursue such research independently. ..
  47. TRANSCRIPTOME ANALYSIS IN NORMAL AND NEOPLASTIC PROSTATE
    Peter Nelson; Fiscal Year: 2002
    ..The accomplishment of these aims will provide a genomics-based resource that defines cell type specific gene expression profiles associated with stages of normal development and neoplastic prostate growth. ..
  48. MOLECULAR ALTERATIONS IN PROSTATE CANCER PROGRESSION
    Peter Nelson; Fiscal Year: 2002
    ..3) Compile and evaluate a panel of cancer-phenotype associated products for prognostic relevance. ..
  49. FOLYLPOLYGLUTAMATE SYNTHETASE IN CANCER CHEMOTHERAPY
    John McGuire; Fiscal Year: 2003
    ..This may explain why high-level resistance to pulse MTX can occur in the absence of a large decrease in total FPGS activity or a rise in glutamyl hydrolase activity. ..
  50. Enhancement of Gene Therapy Outcomes for Fabry Disease
    Jeffrey Medin; Fiscal Year: 2004
    ..Hypothesis: Co-overexpression of the prosaposin gene, a protein co-factor for the a-gal A enzyme, leads to higher catalytic activity in genetically corrected cells than overexpression of a-gal A alone. ..
  51. Chemistry and Pharmacology of a New Nicotine Ligands
    Alan Kozikowski; Fiscal Year: 2007
    ..Functional activity will be evaluated using established 86RbC1 efflux assays and/or whole cell patch clamp measurements. ..
  52. GENE-ENVIRONMENT INTERACTION AND COLON CARCINOGENESIS
    Jia Chen; Fiscal Year: 2002
    ....