TY - JOUR. T1 - Mapping of the active site of glutamate carboxypeptidase II by site-directed mutagenesis. AU - Mlčochová, Petra. AU - Plechanovová, Anna. AU - Bařinka, Cyril. AU - Mahadevan, Daruka. AU - Saldanha, Jose W.. AU - Rulíšek, Lubomír. AU - Konvalinka, Jan. PY - 2007/9. Y1 - 2007/9. N2 - Human glutamate carboxypeptidase II [GCPII (EC 3.4.17.21)] is recognized as a promising pharmacological target for the treatment and imaging of various pathologies, including neurological disorders and prostate cancer. Recently reported crystal structures of GCPII provide structural insight into the organization of the substrate binding cavity and highlight residues implicated in substrate/inhibitor binding in the S1′ site of the enzyme. To complement and extend the structural studies, we constructed a model of GCPII in complex with its substrate, N-acetyl-l-aspartyl-l-glutamate, which enabled us to predict additional amino acid residues interacting with the bound substrate, and used ...

[38 Pages Report] Check for Discount on Glutamate Carboxypeptidase 2 (Folate Hydrolase 1 or Prostate Specific Membrane Antigen or PSMA or Pteroylpoly Gamma Glutamate Carboxypeptidase or Cell Growth Inhibiting Gene 27 Protein or FOLH1 or EC 3.4.17.21) - Pipeline Review, H2 2017 report by Global Markets Direct. Glutamate Carboxypeptidase 2 (Folate Hydrolase 1 or Prostate Specific Membrane...

Recombinant Human Glutamate carboxypeptidase 2 Protein. Synthesized in e. coli. Protein Tag: His. Purity: Greater than 90% as determined by SDS-PAGE. From $88

Low blood folate levels result in hyperhomocysteinemia, which has been associated with increased risk for cardiovascular disease, neural tube defects and cognitive deficits. Intake of dietary folates is the chief determinant of blood folate levels. Molecular defects in the intestinal absorption of dietary folates that precipitate low blood folate levels and hyperhomocysteinemia have not been investigated previously. Dietary folates are a mixture of polyglutamylated folates which are digested to monoglutamyl folates by the action of folylpoly-gamma-glutamate carboxypeptidase (FGCP), an enzyme that is anchored to the intestinal brush border membrane and is expressed by the glutamate carboxypepidase II (GCPII) gene. We cloned GCPII cDNA from human intestine and identified both a full-length transcript and a 93 bp shorter transcript lacking exon 18, consistent with the presence of a splice variant. In addition, we identified an H475Y polymorphism in GCPII in DNA samples from a healthy Caucasian population

Chronic pain often accompanies immune-related diseases with an elevated level of IgG immune complex (IgG-IC) in the serum and/or the affected tissues though the underlying mechanisms are largely unknown. shown that neuronal FcRI triggers a nonselective cation channel, which may contribute to the IgG-IC-induced excitation of DRG neurons[19,30]. Moreover, TRPC3 acts as a novel and crucial downstream transduction channel mediating… More →. ...

Sphingosine-1-phosphate (S1P) can be an important mediator of inflammation recently shown in studies to increase the excitability of small diameter sensory neurons at least in part via activation of the S1P1 receptor subtype. but not its inactive enantiomer, W140. The hyperalgesic effects of S1P were mimicked by intraplantar injection of the well characterized S1PR1 agonist, SEW2871. The development of S1P-induced hyperalgesia was clogged by apocynin, a NADPH oxidase inhibitor, L-NAME, a non-selective NOS inhibitor and by the potent PN decomposition catalysts (FeTM-4-PyP5+ and MnTE-2-PyP5+). Our findings provide mechanistic insight into the signaling pathways engaged by S1P in the development of hyperalgesia and focus on the contribution of the S1P1 receptor-to-PN signaling in this process. [69; 68] at least in part via INCB8761 activation of S1PR1 [11] and that S1P derived following bioconversion of ceramide, contributes to NGF-induced excitation of rat sensory neurons [70; 36]. Interestingly, ...

NAAG is catabolized via NAAG peptidase activity. Two enzymes with NAAG peptidase activity have been cloned, glutamate carboxypeptidase II and glutamate carboxypeptidase III. These enzymes mediate the hydrolysis of NAAG to NAA and glutamate. Their inhibition can produce therapeutic benefits. Two main types of inhibitors of this enzyme are known: compounds related to 2-(phosphonomethyl)pentanedioic acid (2-PMPA) and urea-based analogs of NAAG, including ZJ43, ZJ17, and ZJ11. In rat models, ZJ43 and 2-PMPA reduce perception of inflammatory and neuropathic pain when administered systemically, intracerebrally, or locally, suggesting that NAAG modulates neurotrasmission in pain circuits via mGlu3 receptors. The inhibition of NAAG hydrolysis increases the concentration of NAAG in the synaptic space analogous to the effects of SSRIs in increasing the concentration of serotonin. This elevated NAAG gives greater activation of presynaptic mGluR3 receptors, which decrease release of transmitter (glutamate) ...

SWISS-MODEL Template Library (SMTL) entry for 3d7f.1. A high resolution crystal structure of human glutamate carboxypeptidase II (GCPII) in a complex with DCIT, a urea-based inhibitor

TY - JOUR. T1 - Identification of Naturally Processed Helper T-Cell Epitopes from Prostate-Specific Membrane Antigen Using Peptide-Based in Vitro Stimulation. AU - Kobayashi, Hiroya. AU - Omiya, Ryusuke. AU - Sodey, Benjamin. AU - Yanai, Mitsuru. AU - Oikawa, Kensuke. AU - Sato, Keisuke. AU - Kimura, Shoji. AU - Senju, Satoru. AU - Nishimura, Yasuharu. AU - Tateno, Masatoshi. AU - Celis, Esteban. PY - 2003/11/1. Y1 - 2003/11/1. N2 - Purpose: There is growing evidence that CD4+ helper T lymphocytes (HTLs) play an essential role in the induction and long-term maintenance of antitumor CTL responses. Thus, approaches to develop effective T-cell-based immunotherapy should focus in the stimulation of both CTLs and HTLs reactive against tumor-associated antigens. The present studies were performed with the purpose of identifying HTL epitopes for prostate-specific membrane antigen (PSMA) for the optimization of vaccines for prostate cancer. Experimental Design: Synthetic peptides from regions of the ...

Prostate-specific membrane antigen (PSMA), also known as glutamate carboxypeptidase II (GCPII), is an important diagnostic and therapeutic target in prostate cancer. PSMA/GCPII is also expressed in many healthy tissues, but its function has only been established in the brain and small intestine.

Clone REA408 recognizes the human prostate-specific membrane antigen (PSMA) antigen, a single-pass type II membrane protein which is also known as folate hydrolase 1 (FOLH1), glutamate carboxypeptidase 2 (GCP2), or N-acetylated-alpha-linked acidic dipeptidase I (NAALADase). PSMA is a zinc metallopeptidase which catalyzes the hydrolysis of N-acetylaspartylglutamate to glutamate and N-acetylaspartate. It is expressed with low levels in the small intestine, renal tubular cells, and salivary gland, and is over-expressed in prostate cancer tissue. PSMA is also expressed in the nervous system. Additional information: Clone REA408 displays negligible binding to Fc receptors. | USA

Prostate-specific Membrane Antigen Antibody-Drug Conjugate (PSMA ADC) 1301EXT is an open-label, nonrandomized, phase 1 extension study of PSMA ADC administered IV in subjects with progressive CMPC that has progressed after prior taxane therapy. Subjects who have participated in PSMA ADC 1301 and who, in the opinion of the PI, are likely to benefit from continued treatment with PSMA ADC will be enrolled in PSMA ADC 1301EXT ...

Using human cancer cells, tumour and blood samples from cancer patients, researchers at Johns Hopkins Medicine have uncovered the role of a neurotransmitter in the spread of aggressive cancers.. Neurotransmitters are chemical messengers that transmit impulses from neurons to other target cells.. The work, described in the journal Cell Reports, found that this neurotransmitter, called N-acetyl-aspartyl-glutamate (NAAG) NAAG is more abundant in cancers with a tendency to grow and spread rapidly - or so-called higher grade cancers - than in lower grade tumours, making it a potential marker for tumour progression or regression during cancer therapy, the researchers say.. The experiments also demonstrated that NAAG is a source of glutamate, a chemical that cancer cells use as building blocks to survive, in tumours that express an enzyme called glutamate carboxypeptidase II (GCPII).. The group also discovered that stopping the GCPII from being active by using a drug called 2-PMPA to treat human ...

Solving the Convergence Problem in the Synthesis of Triantennary N-Glycan Relevant to Prostate-Specific Membrane Antigen (PSMA) Journal Article ...

Picture of Chemical structure of prostate-specific membrane antigen (PSMA,.. stock photo, images and stock photography.. Image 16083639.

Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein that is overexpressed in prostate cancer. Radiolabeled small molecules that bind with high affinity to its active extracellular center have emerged as a potential new diagnostic standard of reference for prostate cancer, resulting in images with extraordinary tumor-to-background contrast.

Journal: EJNMMI - European Journal of Nuclear Medicine and Molecular Imaging ArticleTitle: Prostate-specific membrane antigen PET imaging and immunohistochemistry in adenoid cystic carcinoma-a preliminary analysis

View and buy high quality 2-MPPA from Tocris Bioscience. Selective glutamate carboxypeptidase II (GCP II) inhibitor; orally bioavailable.

Abstract: This study addresses the issues in translating the laboratory derived data obtained during discovery phase of research to a clinical setting using a breast cancer model. Laboratory-based risk assessment indi-cated that a family history of breast cancer, reduced folate carrier 1 (RFC1) G80A, thymidylate synthase (TYMS) 5-UTR 28bp tandem repeat, methylene tetrahydrofolate reductase (MTHFR) C677T and catecholamine-O-methyl transferase (COMT) genetic polymorphisms in one-carbon metabolic pathway increase the risk for breast cancer. Glutamate carboxypeptidase II (GCPII) C1561T and cytosolic serine hydroxymethyl transferase (cSHMT) C1420T polymorphisms were found to decrease breast cancer risk. In order to test the clinical validity of this information in the risk prediction of breast cancer, data was stratified based on number of protective alleles into four categories and in each category sensitivity and 1-specificity values were obtained based on the distribution of number of risk ...

ENGLISH ABSTRACT: The primary objective of the study was the development of a polymeric drug delivery system targeting prostate specific membrane antigen (PSMA) by employing amphiphilic poly(N-vinylpyrrolidone) (PVP) as a drug delivery vehicle and tyrothricin as an anti-tumour agent. Three xanthate based reversible addition-fragmentation chain-transfer (RAFT) agents were synthesised, namely: α-succinimide ω-xanthate, α-hydroxyl ω-xanthate, and α-acetal ω-xanthate. The RAFT agents were subsequently employed in the polymerisation of N-vinylpyrrolidone to form α- and ω-heterotelechelic PVP. The α-acetal ω-xanthate heterotelechelic PVP system was selected because of its ability to form aldehyde and thiol/disulphide functionalities on the α- and ω-chain ends respectively in a one pot deprotection strategy. The deprotected PVP was conjugated to a model ligand through Schiff base and reductive animation via the N-terminus and a model drug via thiol-ene Michael addition. Successful ...

The dipeptide N-acetyl-aspartyl-glutamic acid (NAAG) present in brain and spinal cord tissues may act as a neurotransmitter at excitatory synapses in the central nervous system. However, pharmacological and biochemical studies of NAAG are hampered by its rapid inactivation in vivo and in vitro by an enzyme that cleaves NAAG into N-acetyl-aspartate and glutamate. This enzyme has been previously named N-acetylated alpha-linked acidic dipeptidase (NAALADase). Based upon our earlier studies on the specificity of this enzyme, we have now designed new competitive inhibitors of this peptidase. N-Succinyl-glutamic acid, 4, was almost as potent as N-acetyl-beta-aspartyl-glutamic acid (beta-NAAG), 2, in inhibiting the hydrolysis of [Glu-3H]NAAG by rat brain membranes, with an IC50 value in the micromolar range. The analogous affinities of the substrate NAAG and of N-succinyl-glutamic acid suggest that the N-acetyl moiety is not an absolute requirement for entry into the active site of the enzyme. ...

250 µCi quantities of [Glutamate-3, 4-3H]-NAAG are available for your research. Application of [3H]NAAG can be found in: regional distribution and pharmacological characteristics of binding sites in rat brain in neurochemistry, synthesis and release by crayfish nerve fibers (implications for axon-glia signaling) in neuroscience, release of endogenous NAAG and uptake in guinea pig cerebellar slices in brain research, effects of N-acetylated alpha-linked acidic dipeptidase (NAALADase) inhibitors on catabolism in vivo in neuroscience, etc.. ...

(2S)-2-[[2-[2-(2,6-Dichloroanilino)phenyl]acetyl]amino]pentanedioic acid | C19H18Cl2N2O5 | CID 22821282 - structure, chemical names, physical and chemical properties, classification, patents, literature, biological activities, safety/hazards/toxicity information, supplier lists, and more.

2-[[4-[3-(2-Amino-6-methyl-4-sulfanylidene-1H-pyrimidin-5-yl)propylamino]benzoyl]amino]pentanedioic acid | C20H25N5O5S | CID 3561247 - structure, chemical names, physical and chemical properties, classification, patents, literature, biological activities, safety/hazards/toxicity information, supplier lists, and more.

90480-83-4 - Pentanedioic acid, di-C8-10-branched alkyl esters - Searchable synonyms, formulas, resource links, and other chemical information.

目的: 检测前列腺特异性膜抗原(prostate specific membrane antigen,PSMA)基因及蛋白在前列腺癌组织中的表达?方法:分别采用半定量RT-PCR法及免疫组织化学法检测52例前列腺癌组织及35例前列腺增生组织中PSMA基因及蛋白的表达情况?结果:①PSMA在前列腺癌及前列腺增生组织中表达阳性率分别为84.6%(44/52)及68.6%(24/35),虽然前列腺癌组织中PSMA表达阳性率高于前列腺增生组织,但两组阳性率间差异无统计学意义(P > 0.05)?PSMA mRNA半定量结果在两组间存在差异,癌组织中PSMA的表达量明显高于增生组织中的表达(P < 0.05)?②前列腺癌组织中PSMA蛋白表达总阳性率高达94.2%,明显高于增生组织中的阳性率(65.7%),且以++~+++居多?结论:PSMA基因及蛋白的表达在前列腺癌组织均高于前列腺增生组织,提示其可作为前列腺癌诊断指标?;Objective: To investigate the expression of prostate specific membrane antigen(PSMA) gene and protein in

https://doi.org/10.18632/oncotarget.12967 Jae-Hye Lee, Hyun-Soo Cho, Jeong-Ju Lee, Soo Young Jun, Jun-Ho Ahn, Ju-Sik Min, Ji-Yong Yoon, Min-Hyuk Choi, Su-Jin Jeon, Jung Hwa Lim, Cho-Rok Jung, Dae-Soo...

Objective To evaluate the impact/effects of Lutetium-177-PSMA based treatment in improving the quality of life in patients with advanced stage of prostate cancer (mCRPC) Methodology Epidemiology (Global data) Epidemiology (NZ Data) Diagnosis and staging Treatment plan Metastatic disease(mCRPC) Metastatic disease(mCRPC) Metastatic disease(mCRPC) treatment algorithm Metastatic disease(mCRPC) treatment review of literature Prostate specific membrane antigen (PSMA) and mCRPC Various Prostate specific membrane antigen (PSMA) ligands and radionuclides suitable for labelling Lu-177 PSMA based Metastatic disease(mCRPC) treatment review of literature Lu-177-PSMA Treatment outcomes Lu-177 based therapeutic radiopharmaceuticals based treatment outcomes Physiological outcomes of the treatment, at our clinical site QoL, Pain and PSA levels; relative comparison PSA response and QoLoutcomes to Lu-177-PSMA, at our clinical site Third line treatment v/s Lu-177-PSMA Third line treatment v/s Lu-177-PSMA;Feedback ...

Authors: Michael S Hofman, Peter Eu, Price Jackson, Emily Hong, David Binns, Amir Iravani, Declan Murphy, Catherine Mitchell, Shankar Siva, Rodney J Hicks, Jennifer D Young, Philip J Blower, Gregory E Mullen

Our data indicate that PSMA plays a VEGF-independent role in retinal angiogenesis and that the lack of or inhibition of PSMA may represent a novel therapeutic strategy for treatment of angiogenesis-based ocular diseases.

PubMed Central Canada (PMC Canada) provides free access to a stable and permanent online digital archive of full-text, peer-reviewed health and life sciences research publications. It builds on PubMed Central (PMC), the U.S. National Institutes of Health (NIH) free digital archive of biomedical and life sciences journal literature and is a member of the broader PMC International (PMCI) network of e-repositories.

This invention relates to recombinant human monoclonal antibodies which bind to PSMA and related antibody-based compositions aqnd molecules, are disclosed. The human antibodies can be produced in a nonhuman transgenic animal, e.g., a transgenic mouse, capable of producing multiple isotypes of human monoclonal antibodies by undergoing V-D-J recombination and isotype switching. Also disclosed are pharmaceutical compositions comprising the human antibodies, nonhuman transgenic animals and hybridomas which produce the human antibodies, and therapeutic and diagnostic methods for using the human ...

Progenics Pharmaceuticals, Inc., of Tarrytown, N.Y. is a biopharmaceutical company focusing on the development and commercialization of innovative therapeutic products to treat the unmet medical needs of patients with debilitating conditions and life-threatening diseases. The Companys principal programs are directed toward symptom management and supportive care and the treatment of HIV infection and cancer. The Company has five product candidates in clinical development and several others in preclinical development. In symptom management and supportive care, the Company is developing methylnaltrexone (MNTX) to treat the constipation associated with opioid-based pain relievers without interfering with pain relief. MNTX is in pivotal phase 3 clinical testing for treatment of opioid-induced constipation in patients with advanced medical illness. MNTX is also being studied for the management of patients with post-operative bowel dysfunction and relief of opioid-induced constipation in patients with ...

2005, The National Academy of Sciences. Freely available online through the PNAS open access option. Contributed by Pamela J. Bjorkman, March 15, 2005. We thank members of the Bjorkman laboratory for technical assistance and critical reading of the manuscript, Doug Rees and Michael Chan for helpful discussions, the staff at Stanford Synchrotron and Radiation Laboratory and Advanced Light Source for assistance with synchrotron data collection, Adam Paiz for help with crystallization, Peter Snow and Inder Nangiana of the California Institute of Technology Protein Expression Facility for protein expression, Gary Hathaway of the California Institute of Technology Protein/Peptide Microanalysis Facility for mass spectrometry and N-terminal sequencing, Jens Kaiser for assistance with main and the zinc patch, David Mathog of the California Institute of Technology Sequence and Structure Analysis Facility for help with sequence alignments, and Tomas Bzdega and Joseph Neale (Georgetown University, ...

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1. A compound according to formula II ##STR00115## wherein: X and Y are each independently (CHR1)m or C(O); W is H, ═O, --(CHR1)m--(CH2)p--, or --(CH2)p--U; represents the option of having a double bond; L is --C(O)--(C1-C10)alkylene, --[C(O)--(CH(Z)d)--NH]jNR2, R3, --C(O)--(CHR1)--(CH2)p--U--, --(C5-C14)aryl-(C1-C10)alkylene, R7-benzyl, --(C5-C14)heteroaryl-(C1-C10)alkylene, --C(O)-[(CH2)p--V]n--(CH2)q--C(O)--U, [C(O)--CH(Z)d--NH]t--C(O)--(CHR1)m--(CH2)p-- [U]r, --C(S)--NH-benzylene, --C(O)--NH-benzylene, --[C(O)--(CH(Z)d)--NH]s-benzylene-, or --(C1-C10)alkylene-NR4R5; T is selected from the group consisting of H, --(C1-C10)alkylene, RC(O)--(C1-C10)alkylene, NR2R3--(C1-C10)alkylene, --(C5-C14)heteroaryl-(C1-C10)alkylene, --(C5-C14)aryl-(C1-C10)alkylene and R6--(C5-C14)heteroarylene-(C1-C10)alkylene; U is selected from the group consisting of --OR, --COR, --(C5-C14)arylene and --NR4R5; V is selected from the group consisting of --NH--, --NR2-- and --NR2, R3; Z is --(CH2)p--COOH, ...

During the last several years, the prostate-specific membrane antigen (PSMA) and corresponding radiolabeled inhibitors have become one of the most …

A radioimmunoconjugate comprised of the recombinant humanized monoclonal antibody J591 against prostate-specific membrane antigen (PSMA) conjugated to chelator desferrioxamine B (DFO-B) and labeled with the radioisotope zirconium Zr 89 with potential imaging property used in positron emission tomography (PET) imaging. Upon administration of zirconium Zr 89 desferrioxamine B monoclonal antibody huJ591, the antibody moiety binds to the extracellular domain of PSMA, and the radioisotope moiety may be detected using PET, thereby allowing the imaging and quantification of PSMA-expressing tumor cells. PSMA, or folate hydrolase is a cell surface peptidase highly expressed by malignant prostate epithelial cells and vascular endothelial cells of numerous solid tumor malignancies. In addition, upon PET imaging this agent provides high tumor:background tissue ratios. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus ...

Background: Overexpression of prostate-specific membrane antigen (PSMA) in tumor tissue and serum has been linked to increased risk of biochemical recurrence in surgically treated prostate cancer patients, but none of the studies have assessed its association with disease-specific mortality.. Methods: We examined whether high PSMA protein expression in prostate tumor tissue was associated with lethal disease, and with tumor biomarkers of progression, among participants of two U.S.-based cohorts (n = 902, diagnosed 1983-2004). We used Cox proportional hazards regression to calculate multivariable HRs and 95% confidence intervals (CI) of lethal prostate cancer, defined as disease-specific death or development of distant metastases (n = 95). Partial Spearman rank correlation coefficients were used to correlate PSMA with tumor biomarkers.. Results: During an average 13 years of follow-up, higher PSMA expression at prostatectomy was significantly associated with lethal prostate cancer (age-adjusted ...

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The recent implementation of PET with prostate specific membrane antigen (PSMA)-specific radiotracers into the clinical practice has resulted in the significant improvement of accuracy in the detection of prostate carcinoma (PCa). PSMA-expression in ganglia has been regarded as an important pitfall in prostate carcinoma-PET diagnostics but has not found any practical use for diagnosis or therapy. We explored this phenomenon and demonstrated the applicability of peripheral ganglia in healthy rats as surrogates for small PSMA positive lesions for the preclinical evaluation of diagnostic PCa PET probes. Healthy rats were measured with PET/CT using the tracers [18F]DCFPyL, [Al18F]PSMA-11 and [68Ga]PSMA-11. Sections of ganglia were stained with an anti-PSMA antibody. [18F]DCFPyL uptake in ganglia was compared to that in LNCaP tumor xenografts in mice. Whereas [18F]DCFPyL and [68Ga]PSMA-11 were stable in vivo and accumulated in peripheral ganglia, [Al18F]PSMA-11 suffered from fast in vivo deflourination

TY - JOUR. T1 - Semiquantitative Parameters in PSMA-Targeted PET Imaging with [18F]DCFPyL. T2 - Impact of Tumor Burden on Normal Organ Uptake. AU - Werner, Rudolf A.. AU - Bundschuh, Ralph A.. AU - Bundschuh, Lena. AU - Lapa, Constantin. AU - Yin, Yafu. AU - Javadi, Mehrbod S.. AU - Buck, Andreas K.. AU - Higuchi, Takahiro. AU - Pienta, Kenneth J.. AU - Pomper, Martin G.. AU - Lodge, Martin A.. AU - Gorin, Michael A.. AU - Rowe, Steven P.. PY - 2020/2/1. Y1 - 2020/2/1. N2 - Purpose: In this study, we aimed to quantitatively investigate the biodistribution of [18F]DCFPyL in patients with prostate cancer (PCa) and to determine whether uptake in normal organs correlates with an increase in tumor burden. Procedures: Fifty patients who had been imaged with [18F]DCFPyL positron emission tomography/computed tomography (PET/CT) were retrospectively included in this study. Forty of 50 (80 %) demonstrated radiotracer uptake on [18F]DCFPyL PET/CT compatible with sites of PCa. Volumes of interests (VOIs) ...

The prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein that occurs much more commonly in prostate cancer cells compared to benign prostate tissue. One of the PSMA agents under development is 68-gallium-PS-MA-11, which has demonstrated a higher diagnostic efficiency compared to C-11 choline. Detection rates were dependent on PSA values. For example, a 93% detection rate was observed when the PSA was over 2.0 but only 50% when the PSA was 0.2-0.5. There are limitations to PSMA-targeting agents. Not all prostate cancers exhibit PSMA overexpression. In one study, about 8% of prostate cancer patients did not show PSMA overexpression. Benign lesions and several other types of cancers may also exhibit increased PSMA expression. False positive celiac lymph nodes have frequently been noted in the upper abdomen and detection of small locally-recurrent lesions and lymph nodes in the lower pelvis is challenging ...

It has long been known that PSMA is a moving target. The advent of PSMA PET scans has enabled us to track PSMA expression. Cancers that express a lot of PSMA (called PSMA-avid tumors) can be distinguished from cancers that express very little. Radiologists determine avidity by comparing the uptake of the tracer in cells that express PSMA to the uptake of the tracer in cells known to not express PSMA. Early low-grade prostate cancer does not express PSMA at all. Higher grade prostate cancer may express some PSMA. PSMA expression really starts to take off when the cancer metastasizes, although it is highly variable between patients. About 90-95% of metastatic men express at least some PSMA on their prostate cancer cells. At some point, however, as genomic breakdown continues, PSMA is no longer expressed by metastases. Thus, there is an optimal point for treating each patient with PSMA-targeted therapy. Treatment too early or too late, may exert selective pressure on the predominant non-PSMA-types, ...

Page contains details about S,S-2-[3-[5-amino-1- carboxypentyl]ureido]pentanedioic acid-polyethylene glycol-block-poly(2-(diisopropyl amino)ethyl methacrylate):methoxy-polyethylene glycol-block-poly(2-(diisopropyl amino)ethyl methacrylate-co-glycidyl methacrylate-oligoarginine) nanoparticles . It has composition images, properties, Characterization methods, synthesis, applications and reference articles : nano.nature.com

Prostate-specific membrane antigen (PSMA) is a surface protein that is normally present on healthy prostate cells, but is found at much higher levels on prostate cancer cells. It is barely found in the rest of the body. Therefore, PSMA is an ideal target for diagnostic purposes as well as targeted therapies against prostate cancer, says biotechnologist Dr. Matthias Eder of the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ).. Eders group has developed a small molecule (PSMA-617) that is capable of specifically attaching to PSMA and can be labeled with various radioactive substances, called radionuclides. When chemically bound to gallium-68, a weakly radioactive diagnostic radionuclide, PSMA-617 can be used to visualize even the smallest assemblies of prostate cancer cells in PET (positron emission tomography) scans. In this way, physicians are able to detect small secondary tumors in other organs or closely monitor response to therapy. Diagnostic approaches that have ...

December 6, 2017 -- Prostate-specific membrane antigen (PSMA) PET/CT scans can help identify prostate cancer patients with rising levels of prostate-specific antigen (PSA) after radical prostatectomy who can most benefit from salvage radiation treatment, according to a study published in the December issue of the Journal of Nuclear Medicine.. Australian researchers took a somewhat novel approach by investigating whether the use of PSMA PET/CT affected patient response to treatment, not just whether PET scans resulted in a change in management.. In the study, these patients underwent imaging with a PSMA-PET scan and had treatment based on the results of the scan findings, said co-author Dr. Louise Emmett from St. Vincents Hospital in Sydney. The study then followed how these men were treated, and whether the treatment was effective.. The researchers analyzed 146 men; 99 patients received salvage radiation treatment, with an overall treatment response after salvage radiation of 72%. Among the ...

Prostate-specific membrane antigen (PSMA), a type II glycoprotein, is highly expressed in almost all prostate cancers. By playing such a universal role in the disease, PSMA provides a target for diagnostic imaging of prostate cancer using positron emission tomography/computed tomography (PET/CT). The PSMA-targeting ligand Glu-NH-CO-NH-Lys-(Ahx)-HBED-CC (DKFZ-PSMA-11) has superior imaging properties and allows for highly-specific complexation of the generator-based radioisotope Gallium-68 (68Ga). However, only module-based radiolabeling procedures are currently available. This study intended to develop a single vial kit solution to radiolabel buffered DKFZ-PSMA-11 with 68Ga. A 68Ge/68Ga-generator was utilized to yield 68GaCl3 and major aspects of the kit development were assessed, such as radiolabeling performance, quality assurance, and stability. The final product was injected into patients with prostate cancer for PET/CT imaging and the kit performance was evaluated on the basis of the ...

Background: Treatment of metastatic, castrate-resistant prostate cancer (CRPC) remains a highly unmet medical need. We have developed a bispecific SCORPIONTM (multi-specific protein therapeutic) molecule that redirects T cell cytotoxicity against cells expressing PSMA (Prostate Specific Membrane Antigen), a common prostate-cancer related antigen. The SCORPION molecule described here contains two pairs of binding domains, each targeting a unique antigen, linked to opposite ends of an immunoglobulin Fc domain to extend the half-life of the molecule in vivo. In these studies, we examine the ability of a SCORPION molecule targeting both CD3 and PSMA, to inhibit the growth of PSMA expressing tumors in vivo.. Materials and Methods: NOD/SCID mice were implanted with the PSMA(+) prostate tumor cell line C4-2B and purified human T cells in one of two models. In a first model of residual disease, C4-2B cells were coimplanted subcutaneously with human T cells, and treatment with drug was initiated ...

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The study creates autologous gene-modified T cells against prostate specific membrane antigen (PSMA, unrelated to PSA) (designer T cells) by ex vivo modification of patient T cells. T cells are collected by leukopheresis, transported to the RWMC cGMP Cell Manipulation Core and transduced with retrovirus containing a chimeric antigen receptor (CAR) that is expressed on the modified cells. This CAR links specificity of an antibody against PSMA with signaling domains of the T cell and redirects the recognition of the T cells to engage and kill prostate cancer cells anywhere in the body. These are administered at a dose of 10^10 with randomization to either low or moderate Interleukin 2 given by CI (continuous infusion) for one month following the T cell infusion. Subsequent subjects will receive 10^11 cells with Interleukin 2 at either low or moderate dose, in a non randomized manner, depending upon the outcome of the prior cohort. Prior to T cell infusion, all subjects will receive ...

Targeted metallic nanoparticles have shown potential as a platform for development of molecular-specific contrast agents. Aptamers have recently been demonstrated as ideal candidates for molecular targeting applications. In this study, we investigated the development of aptamer-based gold nanoparticles as contrast agents, using aptamers as targeting agents and gold nanoparticles as imaging agents. We devised a novel conjugation approach using an extended aptamer design where the extension is complementary to an oligonucleotide sequence attached to the surface of the gold nanoparticles. The chemical and optical properties of the aptamer−gold conjugates were characterized using size measurements and oligonucleotide quantitation assays. We demonstrate this conjugation approach to create a contrast agent designed for detection of prostate-specific membrane antigen (PSMA), obtaining reflectance images of PSMA(+) and PSMA(−) cell lines treated with the anti-PSMA aptamer−gold conjugates. This ...

Furthermore, disease management such as salvage radiotherapy is best at low PSA levels. Thus, it is critical to capture the disease in the oligometastatic stage as disease progression and commencement of systemic therapies can be delayed by metastasis-directed therapy. Prostate-specific membrane antigen (PSMA) is overexpressed in prostatic cancer cells. Novel imaging modalities using radiolabeled tracers with PSMA such as Ga-PSMA-positron emission tomography (PET)/computed tomography (CT) have shown promising results. We review the literature regarding Ga-PSMA-PET/CT in the setting of primary prostate cancer and biochemical recurrence. At present, the best utilization of Ga-PSMA-PET/CT appears to be in biochemical recurrence. Ga-PSMA-PET/CT has high diagnostic accuracy for lymph node metastases and has been shown to have superior detection rates to conventional imaging, especially at low PSA levels. The exact role of Ga-PSMA-PET/CT in primary prostate cancer is not yet entirely clear. It has an ...

Introduction: Radical prostatectomy (RP) and radical radiotherapy (RT) are well established primary curative options for localized prostate cancer. Despite technical improvements, prostate-specific antigen (PSA)-recurrence after RP and RT is a common clinical scenario. We aimed to assess the role of 68Gallium (68Ga) prostate-specific membrane antigen positron emission tomography computed tomography (PSMA PET/CT) in patients with biochemical recurrence of prostate cancer after RP or RT for the detection and localization recurrent and metastatic disease. Materials and Methods: We ambispectively (70 retrospective and 100 prospective) analyzed the data of men with biochemical recurrence post-RP and post-RT who were evaluated by 68Ga PSMA PET/CT at our institute. We aimed to assess the relationship between serum PSA levels and the probability of having a positive scan in patients with recurrent prostate cancer. Results: The study included 170 men, all had adenocarcinoma of the prostate, 124/170 had ...

Prostate circulating tumor cells (PCTCs) in circulation are shed from either a primary tumor or metastases, which are directly responsible for most prostate cancer deaths. Quantifying exfoliated PCTCs may serve as an indicator for the clinical management of prostate cancer, isolating and removing of PCTCs could potentially reduce prostate cancer metastasis, and culturing and characterizing captured PCTCs could facilitate the development of personalized treatment options. Prostate-specific membrane antigen (PSMA) is an established biomarker for prostate cancer being strongly expressed on prostate tumor cells associated with high-grade primary, androgen independent, and metastatic tumors. ...

To enhance the strength of activation afforded by tumor antigen-specific receptors, we investigated the effect of adding combined CD28 and 4-1BB costimulatory signaling domains to a chimeric antigen receptor (CAR) specific for prostate-specific membrane antigen (PSMA). Having transferred receptors encompassing the CD28, 4-1BB, and/or CD3 cytoplasmic domains in primary human CD8 T cells, we find that the P28BBz receptor, which includes all three signaling domains, is superior to receptors that only include one or two of these domains in promoting cytokine release, in vivo T-cell survival and tumor elimination following intravenous T-cell administration to tumor-bearing severe combined immunodeficient (SCID)/beige mice. Upon in vitro exposure to PSMA, the P28BBZ receptor-induced the strongest PI 3 Kinase/Akt activation and Bcl-X L expression, and the least apoptosis in transduced peripheral blood CD8 T cells. These findings further support the concept of integrating optimized costimulatory ...

0070]Examples of tumor antigens include MAGE, MART-1/Melan-A, gp100, Dipeptidyl peptidase IV (DPPIV), adenosine deaminase-binding protein (ADAbp), cyclophilin b, Colorectal associated antigen (CRC)--C017-1A/GA733, Carcinoembryonic Antigen (CEA) and its antigenic epitopes CAP-1 and CAP-2, etv6, am11, Prostate Specific Antigen (PSA) and its antigenic epitopes PSA-1, PSA-2, and PSA-3, prostate-specific membrane antigen (PSMA), T-cell receptor/CD3-ξ chain, MAGE-family of tumor antigens (e.g., MAGE-A 1, MAGE-A2, MAGE-A3, MAGE-A4, MAGE-A5, MAGE-A6, MAGE-A7, MAGE-A8, MAGE-A9, MAGE-A10, MAGE-A11, MAGE-A 12, MAGE-Xp2 (MAGE-B2), MAGE-Xp3 (MAGE-B3), MAGE-Xp4 (MAGE-B4), MAGE-C1, MAGE-C2, MAGE-C3, MAGE-C4, MAGE-C5), GAGE-family of tumor antigens (e.g., GAGE-1, GAGE-2, GAGE-3, GAGE-4, GAGE-5, GAGE-6, GAGE-7, GAGE-8, GAGE-9), BAGE, RAGE, LAGE-1, NAG, GnT-V, MUM-1, CDK4, tyrosinase, p53, MUC family, HER2/neu, p21 ras, RCAS1, α-fetoprotein, E-cadherin, α-catenin, β-catenin, γ-catenin, p120 ctn, ...

We analyzed real-world clinical outcomes of sequential alpha-/beta-emitter therapy for metastatic castration-resistant prostate cancer (mCRPC). Methods: We assessed safety and overall survival in 26 patients who received lutetium-177-prostate-specific membrane antigen ligand (177Lu-PSMA) following radium-223 in the ongoing non-interventional Radium-223 alpha Emitter Agent Safety Study in mCRPC popUlation for long-teRm Evaluation (REASSURE; NCT02141438). Results: Patients received radium-223 for a median 6 injections and subsequent 177Lu-PSMA for a median 3.5 months (≥4th therapy in 69%). The median time between radium-223 and 177Lu-PSMA treatment was 8 months (range 1-31). Grade 3 hematologic events occurred in 9/26 patients (during or after 177Lu-PSMA treatment in 5/9 patients; 8/9 patients had also received docetaxel). Median overall survival was 28.0 months from radium-223 start and 13.2 months from 177Lu-PSMA start. Conclusion: Although the small sample size precludes definitive ...

REVIEWS RADIOPHARMACOLOGY - RECENT DEVELOPMENTS IN THE FIELD OF RADIOPHARMACEUTICALS The Quarterly Journal of Nuclear Medicine and Molecular Imaging 2015 September;59(3):241-68. Prostate-specific membrane antigen as a target for cancer imaging and therapy. Kiess A. P., Banerjee S. R., Mease R. C., Rowe S. P., Rao A., Foss C. A., Chen Y., Yang X., Cho S. Y., Nimmagadda S., Pomper M. G. ...

Clinical trial has received WCMC IRB and CTSC approval with enrollment of initial 6 subjects at WCMC. An additional 38 subjects enrolled 29 treated at participating sub-sites. Reports submitted to WCMC DSMB in December 2014 with approval to proceed without modifications.

TY - JOUR. T1 - Peptidase inhibitor 16 is a membrane-tethered regulator of chemerin processing in the myocardium. AU - Regn, Michael. AU - Laggerbauer, Bernhard. AU - Jentzsch, Claudia. AU - Ramanujam, Deepak. AU - Ahles, Andrea. AU - Sichler, Sonja. AU - Calzada-Wack, Julia. AU - Koenen, Rory R.. AU - Braun, Attila. AU - Nieswandt, Bernhard. AU - Engelhardt, Stefan. PY - 2016/10. Y1 - 2016/10. KW - Peptidase inhibitor 16 (PI16). KW - Chemerin. KW - RARRES2. KW - TIG2. KW - Protease inhibition. KW - Chemerin processing. U2 - 10.1016/j.yjmcc.2016.08.010. DO - 10.1016/j.yjmcc.2016.08.010. M3 - Article. VL - 99. SP - 57. EP - 64. JO - Journal of Molecular and Cellular Cardiology. JF - Journal of Molecular and Cellular Cardiology. SN - 0022-2828. ER - ...

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