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

We report the development of a new sensitive nested reverse transcription-polymerase chain reaction (RT-PCR) assay, using primers derived from the prostate-specific membrane antigen (PSM) cDNA sequence, to detect an hematogenous spread of prostate adenocarcinoma cells. In 60 patients with a biopsy-proven prostate cancer, PSM and PSA RT-PCR detected circulating prostate cells in 40 and 20 patients, respectively. In pT4 M+ and pT3 M+ disease patients, nested PSM primers detected cells in 28 of 33 patients (85%), whereas nested PSA primers detected cells in 17 of 33 (51%). In patients with organ-confined cancer spread (pT2a and pT2b patients) before radical prostatectomy, nested PSM RT-PCR detected circulating prostatic epithelial cells in 6 of 17 patients (35%), which suggests that an hematogenous spread of prostate cells may occur early in prostate cancer history. Altogether, these results suggest that the detection of PSM-expressing cells in blood may predict the development of cancer in patients without clinically apparent prostate cancer. Nevertheless, the potential application and the clinical significance of detection of hematogenous prostate cells through the use of nested PSM primers need an extensive longitudinal study.
 ...
PMID:Enhanced detection of hematogenous circulating prostatic cells in patients with prostate adenocarcinoma by using nested reverse transcription polymerase chain reaction assay based on prostate-specific membrane antigen. 749 5

We have recently cloned a 2.65-kilobase complementary DNA (cDNA) encoding the prostate-specific membrane antigen (PSM) recognized by the 7E11-C5.3 anti-prostate monoclonal antibody. Immunohistochemical analysis of the LNCaP, DU-145, and PC-3 prostate cancer cell lines for PSM expression using the 7E11-C5.3 antibody reveals intense staining in the LNCaP cells with no detectable expression in both the DU-145 and PC-3 cells. Coupled in vitro transcription/translation of the 2.65-kilobase full-length PSM cDNA yields an M(r) 84,000 protein corresponding to the predicted polypeptide molecular weight of PSM. Posttranslational modification of this protein with pancreatic canine microsomes yields the expected M(r) 100,000 PSM antigen. Following transfection of PC-3 cells with the full-length PSM cDNA in a eukaryotic expression vector, we detect expression of the PSM glycoprotein by Western analysis using the 7E11-C5.3 monoclonal antibody. Ribonuclease protection analysis demonstrates that the expression of PSM mRNA is almost entirely prostate specific in human tissues. PSM expression appears to be highest in hormone-deprived states and is hormonally modulated by steroids, with 5-alpha-dihydrotestosterone down-regulating PSM expression in the human prostate cancer cell line LNCaP by 8-10-fold, testosterone down-regulating PSM by 3-4-fold, and corticosteroids showing no significant effect. Normal and malignant prostatic tissues consistently show high PSM expression, whereas we have noted heterogeneous, and at times absent, expression of PSM in benign prostatic hyperplasia. 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.
 ...
PMID:Expression of the prostate-specific membrane antigen. 751 Oct 53

A highly sensitive nested reverse transcriptase-PCR assay, with primers derived from the prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSM) cDNA sequences, has been used to detect occult hematogenous micrometastatic prostate cells. In 77 patients with prostate cancer, PSM and PSA primers detected circulating prostate cells in 48 (62.3%) and 7 (9.1%) patients, respectively. In treated stage D disease patients, PSM primers detected cells in 16 of 24 patients (66.7%), while PSA primers detected cells in 6 of 24 (25%). In post-radical prostectomy patients with negative serum PSA values, PSM primers detected metastases in 21 of 31 patients (67.7%), whereas PSA primers detected cells in only 1 of 33 (3.0%), indicating that micrometastatic spread may be a relatively early event in prostate cancer. The analysis of 40 individuals without known prostate cancer provides evidence that this assay is highly specific and suggests that PSM expression may predict the development of cancer in patients without clinically apparent prostate cancer. Using PSM primers, we detected micrometastases in 4 of 40 controls, 2 of whom had known benign prostatic hyperplasia and were later found to have previously undetected prostate cancer. The clinical significance of detection of hematogenous micrometastic prostate cells using PSM primers and potential applications of this molecular assay, as well as the assay for PSA, merit further study.
 ...
PMID:Sensitive nested reverse transcription polymerase chain reaction detection of circulating prostatic tumor cells: comparison of prostate-specific membrane antigen and prostate-specific antigen-based assays. 752 94

PSA (prostate specific antigen) and PSMA (prostate specific membrane antigen) serum levels were determined in over 235 prostate cancer patients from 8 different United States clinical urological cancer centers. The clinical data were not known until after the serum assay results were shared with all participants to attempt to eliminate possible clinical bias. PSA values are useful in the clinical diagnosis and staging of prostate cancer patients, and generally fall to low values in response to effective treatment, e.g., surgery, hormones, radiation, chemotherapy. PSMA values are not related to clinical stage but if elevated can fall in response to effective treatments. In contrast, PSMA values can be elevated post-treatment in the presence of very low PSA levels (0.01 to 0.00). The elevated PSMA levels predicted a state of clinical progression or clinical resistance in most cases (> 70%). PSMA levels in this study were of better prognostic value than PSA.
 ...
PMID:Comparison of prostate specific membrane antigen, and prostate specific antigen levels in prostatic cancer patients. 754 69

We examined expression of prostate-specific membrane antigen (PSM) mRNA in normal prostate using reverse transcription-PCR and sequencing. An alternatively spliced variant, PSM', along with the previously described PSM form, was found in normal prostate. PSM' cDNA is shorter (2387 nucleotides) than PSM (2653 nucleotides). The cDNAs are identical except for a 266-nucleotide region near the 5' end of PSM cDNA (nucleotide 114-380) that is absent from PSM'. This deleted region includes the translation initiation codon and codons for the putative transmembrane domain of PSM. Thus, PSM' RNA codes for a protein that has no apparent signal sequence. We verified the existence of spliced mRNA variants in human primary tissue specimens by RNase protection assay. In LNCaP human prostatic cancer cells and in primary prostate tumors, PSM is the dominant form. In contrast, normal human prostate expressed more PSM' than PSM. Benign prostatic hypertrophy samples showed about equal expression of both variants. We quantified the relative expression of each variant by densitometry and compiled a tumor index, which is the ratio of PSM:PSM' level. LNCaP has an index ranging from 9-11, carcinoma of the prostate from 3-6, benign prostatic hypertrophy from 0.75-1.6, and normal prostate from 0.075-0.45. The index reflects the increased expression of PSM over PSM' following the progression from normal to tumor state. This tumor index may be a useful indicator for the measurement of tumor progression. PSM and PSM' may be functionally different proteins as a result of differences in structure or cellular location. We are investigating the prevalence of one form over the other and how it may influence tumor progression.
 ...
PMID:Alternatively spliced variants of prostate-specific membrane antigen RNA: ratio of expression as a potential measurement of progression. 788 49

There is a need for the development of new diagnostic tools for the early detection of prostate cancer. A candidate molecule for a new screening test is a prostate-specific membrane antigen (PSM) recognized by the monoclonal antibody 7E11.C5. We carried out studies aimed at identifying PSM in the serum of normal and benign prostatic hyperplasia (BPH) donors and patients with adenocarcinoma of the prostate, in order to judge whether the development of a serum assay using this marker was feasible. By Western blotting, we found significant levels of PSM in serum samples from prostatic cancer patients, in the seminal fluid of pooled normal donors, in BPH patients, and in normal male sera. Similar to prostate-specific antigen (PSA), PSM was present in seminal plasma in higher concentrations than in serum, and PSM levels in prostatic cancer patients were significantly higher than in normal controls. These data suggest that the development of an assay utilizing the PSM and new monoclonal antibodies directed against the antigen, could provide a feasible test for prostatic cancers.
 ...
PMID:Western blot assay for prostate-specific membrane antigen in serum of prostate cancer patients. 808 37

Dendritic cells (DCs) are "professional" antigen-presenting cells capable of stimulating T-cell proliferation and cytotoxicity when loaded with and presenting specific antigens, including tumor antigens. We demonstrated the stimulation of an autologous cytotoxic T-cell response elicited by DC loaded with autologous tumor cell lysate derived from primary prostate tumor. A candidate tumor antigen is prostate-specific membrane antigen (PSMA), which is overexpressed in prostate cancer patients. We identified a HLA-A2 motif in PSMA, isolated patient DC, loaded peptide into DC, and stimulated autologous T cells to proliferate. The ability to use DC for presentation of either tumor or peptide antigen in an HLA-restricted fashion in order to stimulate T-cell proliferation and cytotoxicity demonstrates the potential of this technology for development of a prostate cancer vaccine.
 ...
PMID:Presentation of prostate tumor antigens by dendritic cells stimulates T-cell proliferation and cytotoxicity. 854 83

Work to date has identified prostate-specific membrane antigen (PSMA) as a membrane-bound glycoprotein with high specificity for prostatic epithelial cells. PSMA reacts with the monoclonal antibody 7E11.C5, which is present in serum, seminal fluid, and prostatic epithelial cells, and is increased in its expression in the presence of a hormone refractory state associated with prostatic cancer. This report confirms these results and further documents the presence of the monoclonal antibody 3F5.4G6, which reacts with the extracellular domain of PSMA. This region of PSMA is also an element present in a truncated version of the protein, so-called PSM'. Immune precipitation with either 7E11.C5 or 3F5.4G6 yields an isolated protein species that are reactive with the reciprocal antibody in Western blot analysis. Thus, 3F5.4G6 recognizes the same PSMA protein as does 7E11.C5, but at different epitopes on essentially opposite ends of the molecule. These two antibodies are well suited for use in a sandwich immunoassay, either one as a capture or detection antibody. Current work on this is underway. This report also confirms that 7E11.C5 Western blots for PSMA are negative with normal human brain tissue. The monoclonal antibody 9H10 does not react with 3F5.4G6 or with 7E11.C5 in studies conducted herein. Moreover, 3F5.4G6 reacts with PSMA found in the LNCaP cell line, but not DU-145 or PC3, which lack PSMA.
 ...
PMID:Measurement of prostate-specific membrane antigen in the serum with a new antibody. 860 2

Prostate specific membrane antigen (PSMA) is a novel prostate marker that is highly expressed in normal prostate as well as in prostate cancer. Its expression is increased in prostate cancer and is found primarily in the prostate. PSMA is considered to be a type II membrane protein with a 54% homology to the transferrin receptor. However, in normal prostate, PSM', an alternatively spliced form of PSMA, is localized in the cytoplasm. The PSMA functions as both a neurocarboxypeptidase and folate hydrolase and may therefore be involved in the neuroendocrine regulation of prostate growth and differentiation. The implication of these findings is currently under investigation. In this article the cloning of the PSMA gene, its possible role as a therapeutic target and its implication as a diagnostic tool with regard to the molecular staging of prostate cancer is reviewed.
 ...
PMID:[Significance of prostate-specific membrane antigen (PSMA). A neurocarboxypeptidase and membrane folate hydrolase]. 899 30

We have cloned the gene encoding the prostate-specific membrane (PSM) antigen, which is recognized by the 7E11C-5 antibody. The antigen is strongly expressed in prostate cancer, and the antibody has been approved for use as an imaging agent for detection of prostatic cancer metastasis. The gene was unique and encoded a type II membrane protein. The only clue to its potential function was found in the cDNA coding sequences from 1250 to 1700, which had a modest but significant homology with transferrin-receptor, demonstrating a 54% homology of nucleic acid sequence. In comparing the mRNA obtained from normal prostate with that obtained from cancerous or lymph node carcinoma of the prostate (LNCaP) cells, normal cells produced a shorter alternative spliced species that encoded a cytosolic form of the protein, and not a membrane protein. It appeared that, as the prostatic cells became cancerous, there was a nearly 100-fold difference in expression of the ratio of the messages encoding the 2 forms, with the cytosolic form (PSM') predominant in normal cells and the membrane form (PSM) predominant in cancer cells. The other tissue in which the membrane antigen form of PSM is highly expressed is the membrane brush border of the small intestine of the proximal, but not distal, small intestine. This is the location of a unique membrane form of a folate hydrolase. This membrane folate hydrolase and its location are necessary in human nutrition because humans require folate, and the folate in foods is poly-gamma-glutamated. Polyglutamated folates cannot be taken into the cells by folate-transporter systems. The ability to take up folate from foods requires the membrane folate hydrolase to sequentially remove the gamma-linked glutamates, freeing folate that can then be transported. PSM antigen has a similar folate hydrolase activity. Others have reported finding an enzyme in the rat brain that functions as an alpha-neurocarboxypeptidase and acts on the abundant brain peptide N-acetylaspartylglutamate to generate glutamate and N-acetylaspartate. The 3'-end of the rat brain enzyme had 84% sequence homology with PSM antigen. Because this enzyme liberates glutamate in the brain, the enzyme is considered to have regulatory activity related to glutamate receptors. Current investigations are underway to determine whether glutamate receptors are present in prostate. Thus, PSM antigen is a unique folate hydrolase-carboxypeptidase that can release glutamate with either gamma-or alpha-linkage. Its enzymatic activity raises a number of questions for consideration. In the normal prostate where the protein is intracellular, is PSM' antigen keeping folate in nonglutamated forms? If so, folate should be able to readily diffuse out of prostate cells, making the prostate gland an organ at risk for localized folate deficiency and carcinogenesis. In prostate tumor cells, with the enzyme outside of the cell, can PSM antigen be used for the activation of cytotoxic prodrugs?
 ...
PMID:Characterization and glutamyl preferring carboxypeptidase function of prostate specific membrane antigen: a novel folate hydrolase. 912 29


1 2 3 4 5 6 7 8 9 10 Next >>