EC:3.4.17.21 - FACTA Search

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Query: EC:3.4.17.21 (prostate-specific membrane antigen)
1,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prostate-specific membrane antigen (PSMA) is a 100 kDa type II transmembrane protein with folate hydrolase and NAALAdase activity. PSMA is highly expressed in prostate cancer and the vasculature of most solid tumors, and is currently the target of a number of diagnostic and therapeutic strategies. PSMA is also expressed in the brain, and is involved in conversion of the major neurotransmitter NAAG (N-acetyl-aspartyl glutamate) to NAA and free glutamate, the levels of which are disrupted in several neurological disorders including multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease and schizophrenia. To facilitate analysis of the role of PSMA in carcinoma we have determined the structural organization of the gene. The gene consists of 19 exons spanning approximately 60 kb of genomic DNA. A 1244 nt portion of the 5' region of the PSMA gene was able to drive the firefly luciferase reporter gene in prostate but not breast-derived cell lines. We have mapped the gene encoding PSMA to 11p11-p12, however a gene homologous, but not identical, to PSMA exists on chromosome 11q14. Analysis of sequence differences between non-coding regions of the two genes suggests duplication and divergence occurred 22 million years ago.
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PMID:Mapping, genomic organization and promoter analysis of the human prostate-specific membrane antigen gene. 983 72

gamma-Glutamyl hydrolase (GH, EC 3.4.19.9) is a lysosomal and secreted glycoprotein that hydrolyzes the gamma-glutamyl tail of antifolate and folate polyglutamates. Tumor cells that have high levels of GH are inherently resistant to classical antifolates, and further resistance can be acquired by elevations in GH following exposure to this class of antitumor agents. The highest level of expression in normal tissues occurs in the liver and kidney in humans. When panels of tumors are compared with normal tissues, GH expression is elevated in cancerous hepatic and breast tissue. A second poly-gamma-glutamate hydrolyzing enzyme, glutamate carboxypeptidase II, is a transmembrane protein whose active site is on the outside of the cell, occurring in the prostate gland, small intestine, brain, kidney, and tumor neovasculature. It is a high-affinity (nanomolar), low-turnover, zinc co-catalytic enzyme. In contrast, GH is a low-affinity (micromolar), high-turnover enzyme that has a cysteine at the active site. Data are presented suggesting that Cys110 is the nucleophile that attacks the gamma-amide linkage and causes hydrolysis. GH is being evaluated as an intracellular target for inhibition in order to enhance the therapeutic activity of antifolates and fluorouracil.
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PMID:Glutamyl hydrolase. pharmacological role and enzymatic characterization. 1073 75

Prostate cancer continues to be the most common cancer and second leading cause of cancer-related death among men. The use of markers, particularly serum-based prostate specific antigen (PSA), has contributed to the rapid rise in diagnosed cases in the late 1980s and early 1990s, but new diagnostic and possible therapeutic markers are needed and are currently being evaluated. One of these, prostate-specific membrane antigen (PSMA), is an approximately 100-kDa type II transmembrane protein originally thought to be highly selectively expressed in all types of prostatic tissue, with expression being upregulated in androgen-depleted or androgen-independent states. The radioimmunoconjugate form of the anti-PSMA monoclonal antibody (mAb) 7E11 is currently being used to diagnose prostate cancer metastasis and recurrence. In addition, Phase I and II trials have started utilizing PSMA in different therapeutic ways, with promising results. Recent exciting work has demonstrated PSMA expression in endothelial cells of vessels restricted to the tumor-associated neovasculature. This finding expands the possible beneficial uses of PSMA, as new anti-PSMA mAbs continue to be developed.
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PMID:Prostate-Specific Membrane Antigen: Much More Than a Prostate Cancer Marker. 1085 38

Prostate cancer remains the most common cancer type in men in the United States. Efforts are increasing to evaluate and to discover diagnostic and therapeutic markers for prostate cancer patients. One of these, prostate-specific membrane antigen (PSMA), is a transmembrane protein highly expressed in all types of prostatic tissue, especially cancer. The radio-immunoconjugate form of the anti-PSMA monoclonal antibody (mAb) 7E11, known as the ProstaScint scan, is currently being used to diagnose prostate cancer metastasis and recurrence. Early promising results from various Phase I and II trials have utilized PSMA as a therapeutic target. Recently, PSMA expression in endothelial cells of tumor-associated neovasculature has been described. PSMA's possible role in malignant angiogenesis newly expands the realm of its possible beneficial uses, especially as new anti-PSMA mAbs continue to be developed and refined.
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PMID:The clinical role of prostate-specific membrane antigen (PSMA). 1247 35

Efforts are increasing to identify and evaluate diagnostic and therapeutic markers for prostate cancer patients. One of these, prostate-specific membrane antigen (PSMA), a transmembrane protein highly expressed in all types of prostatic tissue (eg, benign epithelium, benign prostatic hyperplasia, prostatic intra-epithelial neoplasia and adenocarcinomas, with increased binding affinity for malignant cells), is becoming an increasingly important diagnostic and therapeutic marker, not only for prostate cancer, but possibly for other malignant lesions. Recent studies have demonstrated PSMA expression in endothelial cells of tumor-associated neovasculature (including carcinoma of the colon, breast, bladder, pancreas, kidney and melanoma), thus greatly expanding its possible beneficial role, especially as new anti-PSMA mAbs continue to be developed and refined. Future diagnostic and therapeutic interventions utilizing these antibodies will become increasingly important in not only prostate cancer but perhaps many other different malignancy types.
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PMID:Monoclonal antibodies and prostate-specific membrane antigen. 1524 49

Efforts to evaluate and discover diagnostic and therapeutic markers for prostate cancer continue. One of these, prostate-specific membrane antigen (PSMA), a transmembrane protein expressed in all types of prostatic tissue, remains a useful diagnostic and possibly therapeutic target. The radio-immunoconjugate form of the anti-PSMA monoclonal antibody 7E11 is used in the commercially available and US Food and Drug Administration-approved diagnostic tool, the ProstaScint(R) (Cytogen Corporation, Princeton, NJ) scan. Recent studies have demonstrated other possible useful roles for PSMA as a target, not only in prostate cancer, but in other malignancies.
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PMID:Overview of prostate-specific membrane antigen. 1698 27

Positron emission tomography/computed tomography (PET/CT) with ⁶⁸Ga-PSMA is a non-invasive diagnostic technique to image prostate cancer with increased prostate-specific membrane antigen (PSMA) expression. PSMA is a transmembrane protein present in all prostatic tissues. Increased PSMA expression is seen in several malignancies, although prostate cancer is the tumour where it presents higher concentrations. Almost all prostate adenocarcinomas show PSMA expression in most of lesions, primary and metastatic. Immunohistochemistry has demonstrated that the expression of PSMA increases in patients with de-differentiated, metastatic or hormone-refractory tumours. Moreover, the expression level of PSMA has a prognostic value for disease outcome. PET measures the three-dimensional distribution of ⁶⁸Ga-PSMA, producing semi-quantitative images that allow for non-invasive assessment of PSMA expression.
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PMID:⁶⁸Ga-PSMA PET/CT in prostate cancer. 2894 66

The prostate-specific membrane antigen (PSMA) is a transmembrane protein with elevated expression in prostate cancer cells. Breast cancer also shows PSMA expression. We present the case of a 30-year-old woman with triple-negative bilateral breast carcinoma who underwent bilateral mastectomy, chemotherapy, and radiotherapy. She developed a left chest wall and liver recurrence after primary therapy. Her recurrent disease was also triple-negative. In view of the known poor prognosis and very limited therapeutic options, we performed Ga-PSMA PET/CT scan to explore the possibility of PSMA-based therapy as a future option after exhausting standard-of-care treatments.
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PMID:68Ga-Prostate-Specific Membrane Antigen PET/CT in Triple-Negative Breast Cancer. 2957 72

Natural history of prostate cancer (PCa) is extremely variable, as it ranges from indolent and slow growing tumors to highly aggressive histotypes. Genetic background and environmental factors co-operate to the genesis and clinical manifestation of the tumor and include among the others race, family, specific gene variants (i.e., BRCA1 and BRCA2 mutations), acute and chronic inflammation, infections, diet and drugs. In this scenario, remaining actual the clinical interest of bone scan (BS) in detecting skeletal metastases, an important role in diagnostic imaging may be also carried out by, positron emission tomography/computed tomography (PET/CT) and PET/magnetic resonance imaging (PET/MRI), which combine morphological information provided by CT and MRI with functional and metabolic data provided by PET acquisitions. With respect to PET radiotracers, being ancillary the usefulness of F-18 fluoro-deoxyglucose and not yet demonstrated the cost-effectiveness of F-18 Fluoride respect to BS, the main role is now played by choline derivatives, in particular by 11C-choline and 18F-fluorocholine. More recently, a greater interest for both diagnostic and therapeutic purposes has been associated with radiotracers directed to prostate-specific membrane antigen (PSMA), a transmembrane protein expressed on the cell surface, which showed high selective expression in PCa, metastatic lymph nodes and bone metastases. Several PSMA-targeted PET tracers have been developed many of which showing promising results for accurate diagnosis and staging of primary PCa and re-staging after biochemical recurrence, even in case of low prostate specific antigen values. In particular, the most widely used PSMA ligand for PET imaging is a ⁶⁸Ga-labelled PSMA inhibitor, ⁶⁸Ga-PSMA-HBED-CC (⁶⁸Ga-PSMA-11). ^99mTc-HYNIC-Glu-Urea-A for single photon emission computed tomography, and ¹⁷⁷Lu-PSMA-617 for radioligand therapy has also been applied in humans, with interesting preliminary results related to a possible theranostic approach. A potential role of PSMA radioligands in radio-guided surgery has also been proposed.
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PMID:Nuclear Medicine in Prostate Cancer: A New Era for Radiotracers. 2971 80

Expressed on virtually all prostate cancers and their metastases, the transmembrane protein prostate-specific membrane antigen (PSMA) provides a valuable target for the imaging of prostate cancer. Not only does PSMA provide a target for noninvasive diagnostic imaging, e.g., PSMA-positron emission tomography (PSMA-PET), it can also be used to guide surgical resections of PSMA-positive lesions. The latter characteristic has led to the development of a plethora of PSMA-targeted tracers, i.e., radiolabeled, fluorescent, or hybrid. With image-guided surgery applications in mind, this review discusses these compounds based on clinical need. Here, the focus is on the chemical aspects (e.g., imaging label, spacer moiety, and targeting vector) and their impact on in vitro and in vivo tracer characteristics (e.g., affinity, tumor uptake, and clearance pattern).
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PMID:Image-Guided Surgery: Are We Getting the Most Out of Small-Molecule Prostate-Specific-Membrane-Antigen-Targeted Tracers? 3185 10

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