Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prostate cancer is the most common malignant disease in men in western societies. Extracapsular spread of carcinoma is found in approximately half of the patients that are treated by radical prostatectomy. Recently, a new prostate-specific membrane glycoprotein was cloned and sequenced. A highly sensitive and specific nested reverse transcriptase polymerase chain reaction has been developed to detect early occult haematogeneous micrometastatic prostate cells. We analysed venous samples from 17 patients with metastatic prostate cancer using a modified reaction assay. This showed presence of micrometastatic prostate cells in 14 patients. Molecular detection of circulating prostatic epithelial cells could improve clinical staging and treatment of early prostate cancer.
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PMID:[Prostate-specific membrane antigen. A new sensitive molecular indicator in metastasizing prostatic cancer]. 863 73

Prostate cancer is one of the most commonly diagnosed cancers and is a major cause of cancer death in men. Although the majority of the diagnosed prostate cancers will remain localized and never produce clinical symptoms during the lifetime of the host, a subset of these cancers will progress to a more malignant state requiring therapeutic intervention. Acquisition of metastatic ability by prostatic cancer cells is the most lethal aspect of prostatic cancer progression. Once this has occurred, definitive therapy is required before the initially localized metastatic cells escape from the prostate. At present, metastatic prostate cancer is incurable. Therefore, there is an urgent need to develop molecular markers that can be used to predict the metastatic potential of prostate cancers. Using somatic cell hybridization, we have demonstrated that acquisition of metastatic ability requires both the loss of metastasis-suppressor function(s) and the activation of oncogenes. In further studies using micro-cell-mediated chromosomal transfer, we located genes on human chromosome, 8, 10cen-q23, 11p11.2-13, and 17pter-q23, which, when introduced into rat prostatic cancer cells, are capable of suppressing their metastatic ability without affecting their tumorigenicity or growth rate in vivo. Initially we focused upon the human chromosome 11p11.2-13 region to clone metastasis-suppressor gene(s) positionally. One such gene, termed KAI-1, encodes a membrane glycoprotein. KAI-1 has been mapped to the p11.2 region of human chromosome 11 by fluorescence in-situ hybridization analysis. Expression of KAI-1 has been detected in all normal human tissues thus far tested, including prostate tissue. When introduced into rat metastatic prostatic cancer cells, KAI-1 significantly suppressed the metastasis without affecting the tumor growth rate. KAI-1 expression is high in human normal prostate and benign prostatic hyperplasia but is dramatically lower in cancer cell lines derived from metastatic prostate tumors.
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PMID:Prostate cancer--biology of metastasis and its clinical implications. 880 97

We have used microcell fusion-mediated chromosomal transfer to introduce normal human chromosomes into highly metastatic rodent prostatic cancer cells to map the location of a metastasis suppressor gene(s). Using this approach, several chromosomal regions have been identified that harbor such metastatic suppressor genes, including human chromosome 11 between p11.2-13 (T. Ichikawa et al., Cancer Res., 52: 3486-3490, 1992, 54: 2299-2302, 1994; N. Nihei et al., Genes Chromosomes & Cancer, 14: 112-119, 1995; C. W. Rinker-Schaeffer et al., Cancer Res., 54: 6249-6256, 1994). Using positional cloning, a metastatic suppressor gene, termed KAI1, was identified, which is located at human chromosome 11p11.2 (5). Overexpression of KAI1 results in metastasis suppression in certain highly metastatic Dunning R-3327 rat prostatic cancer sublines, such as AT6.1, without metastasis suppression in other highly metastatic sublines, such as AT3.1. This suggests that an additional metastasis suppressor gene is located within the human chromosome 11p11.2-13 region. The CD44 gene is located on human chromosome 11p13 and encodes an integral membrane glycoprotein that participates in specific cell-cell and cell-extracellular matrix interactions. Down-regulation of CD44 expression both at the mRNA and protein levels correlates with metastatic potential within the Dunning system of rat prostatic cancer sublines. Transfection-induced enhanced expression of the Mr 85,000 standard form of CD44 in the highly metastatic AT3.1 rat prostatic cells greatly suppresses their metastatic ability to the lungs without suppression of their in vivo growth rate or tumorigenicity. These results suggest that CD44 is a metastasis suppressor for prostatic cancer and that decreased expression of the standard form of CD44 is involved in the progression of prostatic cancer to a metastatic state.
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PMID:CD44 is a metastasis suppressor gene for prostatic cancer located on human chromosome 11p13. 904 Nov 84

Prostate-specific membrane antigen (PSMA), initially defined by monoclonal antibody (mAb) 7E11, is a now well-characterized type 2 integral membrane glycoprotein expressed in a highly restricted manner by prostate epithelial cells. 7E11 has been shown to bind an intracellular epitope of PSMA that, in viable cells, is not available for binding. Herein, we report the initial characterization of the first four reported IgG mAbs that bind the external domain of PSMA. Competitive binding studies indicate these antibodies define two distinct, noncompeting epitopes on the extracellular domain of PSMA. In contrast to 7E11, these mAbs bind to viable LNCaP cells in vitro. In addition, they show strong immunohistochemical reactivity to tissue sections of prostate epithelia, including prostate cancer. These mAbs were also strongly reactive with vascular endothelium within a wide variety of carcinomas (including lung, colon, breast, and others) but not with normal vascular endothelium. These antibodies should prove useful for in vivo targeting to prostate cancer, as well as to the vascular compartment of a wide variety of carcinomas.
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PMID:Monoclonal antibodies to the extracellular domain of prostate-specific membrane antigen also react with tumor vascular endothelium. 928 60

Prostate cancer is the most common cancer and the second leading cause of cancer-related death among men. New prostatic markers are needed to increase diagnostic and prognostic effectiveness. One such new marker is prostate-specific membrane antigen (PSMA). PSMA is a highly prostate-restricted membrane glycoprotein that is expressed in normal prostatic epithelial cells and elevated in prostate cancers, especially in poorly differentiated, metastatic, and hormone refractory carcinomas. It has been measured in serum with immunocompetitive and Western blot assays, and its levels have been found to be correlated with the prediction of treatment failure and disease prognosis. Reverse transcriptase-polymerase chain reaction (RT-PCR) assays with primers specific for PSMA have been shown to be more effective than PSA-specific primers in detecting hematogenous circulating prostate cancer cells; however, no clear benefit in patient staging or utility as a predictor of clinical outcome or response to treatment has so far been obtained using RT-PCR methods. PSMA is currently utilized as an immunoscintigraphic target using the antibody conjugate CYT-356 (ProstaScint; Cytogen, Princeton, NJ) and has been shown to have clinical value, particularly in detecting occult prostate cancer. Another current application of PSMA is in immunotherapy of prostate cancer, in which promising results have been obtained in a phase I trial, and a phase II trial is underway. The research summarized in this article indicates that PSMA is an excellent target for diagnostic and therapeutic applications in prostate cancer.
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PMID:Prostate-specific membrane antigen: current and future utility. 950 77

Prostate-specific membrane antigen (PSMA) is a type II integral membrane glycoprotein that was initially characterized by the monoclonal antibody (mAb) 7E11. PSMA is highly expressed in prostate secretory-acinar epithelium and prostate cancer as well as in several extraprostatic tissues. Recent evidence suggests that PSMA is also expressed in tumor-associated neovasculature. We examined the immunohistochemical characteristics of 7E11 and those of four recently developed anti-PSMA mAbs (J591, J415, and Hybritech PEQ226.5 and PM2J004.5), each of which binds a distinct epitope of PSMA. Using the streptavidin-biotin method, we evaluated these mAbs in viable prostate cancer cell lines and various fresh-frozen benign and malignant tissue specimens. In the latter, we compared the localization of the anti-PSMA mAbs to that of the anti-endothelial cell mAb CD34. With rare exceptions, all five anti-PSMA mAbs reacted strongly with the neovasculature of a wide spectrum of malignant neoplasms: conventional (clear cell) renal carcinoma (11 of 11 cases), transitional cell carcinoma of the urinary bladder (6 of 6 cases), testicular embryonal carcinoma (1 of 1 case), colonic adenocarcinoma (5 of 5 cases), neuroendocrine carcinoma (5 of 5 cases), glioblastoma multiforme (1 of 1 cases), malignant melanoma (5 of 5 cases), pancreatic duct carcinoma (4 of 4 cases), non-small cell lung carcinoma (5 of 5 cases), soft tissue sarcoma (5 of 6 cases), breast carcinoma (5 of 6 cases), and prostatic adenocarcinoma (2 of 12 cases). Localization of the anti-PSMA mAbs to tumor-associated neovasculature was confirmed by CD34 immunohistochemistry in sequential tissue sections. Normal vascular endothelium in non-cancer-bearing tissue was consistently PSMA negative. The anti-PSMA mAbs reacted with the neoplastic cells of prostatic adenocarcinoma (12 of 12 cases) but not with the neoplastic cells of any other tumor type, including those of benign and malignant vascular tumors (0 of 3 hemangiomas, 0 of 1 hemangioendothelioma, and 0 of 1 angiosarcoma). The mAbs to the extracellular PSMA domain (J591, J415, and Hybritech PEQ226.5) bound viable prostate cancer cells (LNCaP and PC3-PIP), whereas the mAbs to the intracellular domain (7E11 and Hybritech PM2J004.5) did not. All five anti-PSMA mAbs reacted with fresh-frozen benign prostate secretory-acinar epithelium (28 of 28 cases), duodenal columnar (brush border) epithelium (11 of 11 cases), proximal renal tubular epithelium (5 of 5 cases), colonic ganglion cells (1 of 12 cases), and benign breast epithelium (8 of 8 cases). A subset of skeletal muscle cells was positive with 7E11 (7 of 7 cases) and negative with the other four anti-PSMA mAbs. PSMA was consistently expressed in the neovasculature of a wide variety of malignant neoplasms and may be an effective target for mAb-based antineovasculature therapy.
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PMID:Five different anti-prostate-specific membrane antigen (PSMA) antibodies confirm PSMA expression in tumor-associated neovasculature. 1039 65

Over the past two decades, monoclonal antibody technology has had an increasing impact on clinical diagnostic and therapeutic options, and this is true in the realm of managing prostate cancer. Several targets such as prostate-specific antigen and prostatic acid phosphatase as well as, more recently, angiogenic antigens such as vascular endothelial growth factor have been examined for therapy. Prostate-specific membrane antigen, a type II integral membrane glycoprotein initially characterized by the monoclonal antibody 7E11, has shown promise. Recent evidence suggests that prostate-specific membrane antigen is also expressed in tumor-associated neovasculature of a wide variety of malignant neoplasms. With its expression in prostate secretory-acinar epithelium and the prostate and in the neovasculature associated with tumors, prostate-specific membrane antigen represents an excellent antigenic target for monoclonal antibody diagnostic and therapeutic options. As research continues, the role of monoclonal antibody imaging and therapy will become increasingly important in the management of prostate cancer.
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PMID:Monoclonal antibodies: will they become an integral part of the evaluation and treatment of prostate cancer--focus on prostate-specific membrane antigen? 1057 76

Human Prostate Specific Membrane Antigen (PSMA), also known as folate hydrolase I (FOLH1), is a 750-amino acid type II membrane glycoprotein, which is primarily expressed in normal human prostate epithelium and is upregulated in prostate cancer, including metastatic disease. We have cloned and sequenced the mouse homolog of PSMA, which we have termed Folh1, and have found that it is not expressed in the mouse prostate, but primarily in the brain and kidney. We have demonstrated that Folh1, like its human counterpart, is a glutamate-preferring carboxypeptidase, which has at least two enzymatic activities: (1) N-acetylated alpha-linked L-amino dipeptidase (NAALADase), an enzyme involved in regulation of excitatory signaling in the brain, and (2) a gamma-glutamyl carboxypeptidase (folate hydrolase). The 2,256-nt open reading frame of Folh1 encodes for a 752-amino acid protein, with 86% identity and 91% similarity to the human PSMA amino acid sequence. Cells transfected with Folh1 gained both NAALADase and folate hydrolase activities. Examination of tissues for NAALADase activity correlated with the mRNA expression pattern for Folh1. Fluorescent in situ hybridization (FISH) revealed Folh1 maps to only one locus in the mouse genome, Chromosome 7D1-2.
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PMID:Cloning, expression, genomic localization, and enzymatic activities of the mouse homolog of prostate-specific membrane antigen/NAALADase/folate hydrolase. 1121 Jan 80

We have recently identified the TSLC1 gene as a novel tumor suppressor in human non-small cell lung cancers. TSLC1 encodes a membrane glycoprotein with an extracellular domain homologous to those of immunoglobulin superfamily proteins. Truncation of TSLC1 in the cytoplasmic domain in a primary human tumor suggests that this domain is important for tumor suppressor activity. Here, we report the isolation of two TSLC1-like genes, TSLL1 and TSLL2, based on their structural homology with the sequences corresponding to the cytoplasmic domain of TSLC1. Significant similarity was also observed in the extracellular domain as well as in the overall gene structure, indicating that these three genes form a unique subfamily (the TSLC1-gene family) in the immunoglobulin superfamily genes. In contrast to the ubiquitous expression of TSLC1, TSLL1 is expressed exclusively in adult and fetal human brain, while TSLL2 is expressed in several specific tissues including prostate, brain, kidney and some other organs. Expression of TSLL1 and TSLL2 was lost or markedly reduced in many human glioma cell lines or some prostate cancer cell lines, suggesting that loss of expression of these genes might be involved in some human cancers.
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PMID:Isolation of the TSLL1 and TSLL2 genes, members of the tumor suppressor TSLC1 gene family encoding transmembrane proteins. 1153 53

The coxsackievirus and adenovirus receptor (CAR) is a membrane glycoprotein with a cytoplasmic domain, a transmembrane domain and an extracellular region consisting of two immunoglobulin-like domains, an amino-terminal immunoglobulin variable (IgV)-related domain (D1), which is distal to the cell surface, and a proximal IgC2 domain (D2). The coxsackievirus and adenovirus receptor has been shown to exhibit tumour suppression activity in human bladder and prostate cancer cells. In the current paper, we demonstrate that CAR is a tumour suppressor in glioma cells and that the extracellular D2 domain is not required for this inhibitory effect. This finding provides a biological basis for the observation that expression of CAR is downregulated in malignant glioma cells. This suggests that strategies to redirect adenoviruses to achieve CAR-independent infection will be necessary to realise the full potential of adenoviral vectors for cancer gene therapy.
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PMID:The coxsackievirus and adenovirus receptor acts as a tumour suppressor in malignant glioma cells. 1277 71


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