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)

Sulfated glycoprotein-2 (SGP-2) expression has been associated with programmed cell death in the prostate, but its exact role remains unclear. The present study was carried out in an attempt to establish the function of SGP-2 in programmed cell death using tumor necrosis factor (TNF) alpha-induced cytotoxicity in LNCaP cells as the model system. LNCaP is an androgen-sensitive, human prostatic cancer cell line that responds to TNF in culture by undergoing programmed cell death, as determined by the loss of cell number, failure to exclude trypan blue, detection of DNA fragmentation, and increased release of previously incorporated [3H]thymidine. Immunocytochemical staining for SGP-2 was weak but evident in LNCaP cells. Following treatment with TNF alpha, there was a time-dependent increase in SGP-2 staining, the intensity of which peaked at 2 h and declined thereafter. SGP-2 staining in LNCaP cells was undetectable prior to the onset of DNA fragmentation at 6 h of TNF treatment. This observation indicated that TNF-induced cell death in LNCaP cells was characterized by an initial transient elevation of SGP-2, followed by a period of SGP-2 depletion that preceded cell death. Transfection of LNCaP with a 21-base oligonucleotide antisense to SGP-2 resulted in a significant increase in cell death that was sequence specific and was accompanied by a reduction in SGP-2 biosynthesis. These findings supported the concept that SGP-2 depletion, rather than its expression, was associated with cell death. Finally, stable transfection and subsequent overexpression of SGP-2 in LNCaP cells resulted in resistance to the cytotoxic effect of TNF. These results have provided evidence to indicate that SGP-2 plays a role in the protection of TNF-induced cell death in LNCaP cells.
 ...
PMID:Prevention of cell death induced by tumor necrosis factor alpha in LNCaP cells by overexpression of sulfated glycoprotein-2 (clusterin). 775 97

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

Since its identification in seminal fluid in 1971, much new information has been obtained about the biology and expression of prostate-specific antigen (PSA). PSA is a glycoprotein composed of 93% amino acids and 7% carbohydrates, with a molecular weight of about 30,000 Da. Functionally and structurally PSA is a kallikrein-like serine protease, and its physiologic role is degradation of the major proteins of seminal coagulum (semenogelin I and II, fibronectin), which leads to semen liquefaction. The PSA gene is located on the 13q region of chromosome 19, and it has a high degree of homology (more than 80%) with genes of the human glandular kallikrein (hKGK1). PSA production and expression are preferentially but not exclusively associated to the normal, benign hyperplastic and cancerous tissues of the prostate. In fact, it has been demonstrated that PSA is also present in accessory male sex glands and breast cancer. It was recently reported that PSA was also present in milk of lactating women. Many factors may influence PSA synthesis and production, and among them the most important are androgen, retinoic acid and growth factor stimulation. Significant advances have been recently made as regards the molecular isoforms of PSA. In the seminal fluid PSA seems partially bound to a serpine (protein C inhibitor), whereas in serum it is predominantly associated to alpha-1-antichymotrypsin and in a small quantity to alpha-2-macroglobulin. These new findings will have implications for the clinical application of PSA as a tumor marker for prostate cancer.
 ...
PMID:Biochemical characteristics and recent biological knowledge on prostate-specific antigen. 862 11

A-80 is a mucin-like glycoprotein associated with exocrine differentiation that shows little or no expression in normal exocrine cells and typical adenomas, but is upregulated in dysplasia and adenocarcinoma of certain organs. Its expression has not been systematically examined in prostatic adenocarcinoma and its putative precursor, prostatic intraepithelial neoplasia (PIN). The authors applied a mouse monoclonal antibody against A-80 in paraffin-embedded sections from 103 cases of prostatic carcinoma, 26 cases of nodular hyperplasia, 7 autopsy samples from normal young adult prostates, and 12 fetal prostates. All but one cancer reacted, although expression was heterogeneous; 75 of 103 stained extensively (> 3+ on a 0 to 5+ scale) and strongly. Staining extent and intensity were independent of tumor grade, and tended to be strong even when focal. Seventy-seven of 84 foci (92%) of high-grade PIN and 38 of 52 foci (73%) of low-grade PIN stained for A-80; reactions were most extensive and intense in high grade PIN. Only 5 of 26 cases (19%) of hyperplasia reacted, and this consisted of weak to moderate staining in sporadic cells; the remainder were negative. Normal adult prostatic epithelium did not express A-80 except for weak and inconsistent staining in foci of inflammation and infarction; atrophic glands were negative. Fetal prostate showed focally strong reactivity. These results indicate that A-80 is selectively expressed in most cases of intraepithelial neoplasia and prostate cancer, but is usually absent in benign and hyperplastic epithelium. The upregulation of glycoprotein A-80 in PIN and adenocarcinoma parallels observations in other organs, such as the breast and colon, suggesting that this is a significant oncodevelopmental molecule with potential clinical applications.
 ...
PMID:Immunolocalization of glycoprotein A-80 in prostatic carcinoma and prostatic intraepithelial neoplasia. 866 63

Tumour serum markers represent one of the most interesting challenges in modern oncology. Although know for many years, tumour markers did not receive clinical attention until the '80s. Despite their widespread use, the identification of a tumour marker which is highly sensitive as well as specific for a certain type of cancer, and can be assayed by simple, reproducible and cheap methods, remains elusive. This review deals with the clinical use of the Prostate Specific Antigen (PSA). PSA is biochemically a glycoprotein, is the most valuable tool available for the diagnosis and staging of prostate cancer and one of the most widely used laboratory tests in oncology. Serum PSA can detect twice as many prostate cancers as digital rectal examination can and approximately 70% of these cancers are potentially curable. In assessing the role of PSA in the diagnosis and the monitoring of prostate cancer, new concepts have been developed and are in clinical use today: PSA velocity, free versus complexed PSA, PSA index or PSA density and age-specific reference ranges. By combining serum PSA concentration with histologic grade (Gleason grading system) and clinical stage (TNM staging system), we can predict metastasis to the pelvic lymph nodes. For instance, patients with clinical stage T1a-T2b, Gleason grade 1 or 2 and serum PSA level 17.1 ng/ml or less, have a probability of pelvic lymph nodes involvement approaching zero. So, surgical staging procedures can be avoided in these selected patients. Another group of patients with prostate cancer who can benefit from measuring serum PSA concentration, is the group of newly diagnosed patients, with no skeletal symptoms and a serum PSA concentration less than 10 ng/ml. In this group, the probability of a positive bone scan approaches zero and a staging bone scan is not necessary. From the standpoint of economic analysis, measurement of serum PSA can serve in two ways: Firstly, estimating the savings when PSA is used in a prevention programme in the general population and secondly, calculating the savings in patients with prostate cancer, when PSA is used to complement or substitute other diagnostic or staging procedures.
 ...
PMID:Tumour serum markers: clinical and economical aspects. 869 57

Three specimens of localized amyloidosis of the seminal vesicle surgically removed for prostatic cancer were immunohistochemically analyzed to clarify the nature of the permanganate-sensitive congophilic subepithelial deposition. A variety of known amyloidogenic substances and secretory products in the seminal fluid were screened using the indirect immunoperoxidase method. In addition to reactivities with antibodies to amyloid P component and human seminal plasma, the amyloid material was immunoreactive for lactoferrin using a rabbit antiserum and two of three mouse monoclonal antibodies. All the antibodies labeled some of the normal seminal vesicle epithelial cells for this ironbinding, bacteriostatic glycoprotein. In the prostate without accompanying amyloid deposition, a considerable proportion of the glandular epithelium and secretory material were positive for lactoferrin. Pre-embedding immunoelectron microscopy showed lactoferrin immunoreactivity on the amyloid fibrils. Focal staining of the amyloid for gross cystic disease fluid protein-15 was also observed in two lesions. These findings strongly suggest that lactoferrin is the major constituent in localized senile amyloidosis of the seminal vesicle.
 ...
PMID:Localized amyloidosis of the seminal vesicle: identification of lactoferrin immunoreactivity in the amyloid material. 887 4

LNCaP cells, derived from an androgen-sensitive cell line widely employed as an in vitro model of human prostate cancer, have been shown to express activin receptors. Activin is a local regulator of cellular growth, appears to play a key role in mesoderm induction and differentiation during development, and has been implicated in gonadal tumorigenesis. Follistatin, a monomeric glycoprotein that specifically binds and neutralizes activin, is often coexpressed with activin and, thus, modulates the autocrine/paracrine biological activity of this potent growth factor. We tested the hypothesis that LNCaP growth is modulated by the activin/follistatin system. Recombinant human activin A inhibited [3H]thymidine incorporation in a dose-dependent fashion with an ED50 of approximately 0.43 +/- 0.3 nM. Activin (0.1-3 nM) also inhibited dihydrotestosterone (DHT)-stimulated [3H]thymidine incorporation in LNCaP cells. Similarly, recombinant human inhibin A inhibited LNCaP proliferation, but was only 1/100th as potent as activin. Furthermore, activin (3 nM) induced a 3-fold increase in the extent of labeling of low mol wt DNA fragments typical of apoptosis. Activin-induced apoptosis was also indicated by an increase in the number of cells with reduced DNA content, as measured by flow cytometry of activin-treated cells. Both activin-mediated inhibition of cell proliferation and induction of apoptosis could be completely blocked by recombinant human follistatin. Based upon these results using an in vitro model, we speculate that activin functions locally to oppose androgen-driven cell proliferation and, thus, is a key factor controlling prostate growth. Reduced activin biosynthesis, increased follistatin secretion, or signaling defects in the activin receptor system should be further investigated in future studies as potential mechanisms underlying enhanced androgen-independent growth of human prostate cancer cells.
 ...
PMID:Activin inhibits basal and androgen-stimulated proliferation and induces apoptosis in the human prostatic cancer cell line, LNCaP. 894 Mar 74

Since PSA was discovered nearly 20 years ago, significant progress has been made in improving the clinical utility of this glycoprotein as a tumor marker. Factors contributing to the initial limitations in sensitivity and specificity of PSA as a diagnostic tool for early cancer now are understood better. As a result, PSA now is being used [table: see text] widely for the diagnosis of early, curable prostate cancer. PSA, however, because of the inability to differentiate benign processes from malignancy, fails to perform at the ideal tumor-marker level. Nevertheless, in 1997, it remains the best tumor marker in all cancer biology. The research that has been conducted by several independent investigators, showing the correlation between PSA, prostate volume, and patient age, was a vital step in the process of improving the clinical and diagnostic utility of PSA. From this, Oesterling, Dalkin, DeAntoni and others have recommended similar age-specific reference ranges for serum PSA. Subsequent investigations have supported the initial theories that the use of age-specific reference ranges would improve the sensitivity of PSA in younger men, leading to the diagnosis of additional early, organ-confined prostate cancer. The issue of improved specificity in older men has been somewhat less straightforward in that decreasing negative biopsies also result in undetected prostate cancers. The real question involves determining what percent of these undetected prostate cancers are clinically significant to the older patient. Of additional significance is the determination of differing age-specific reference ranges in whites, Asians, and African-Americans (Table 1). In 1997, it is important to know not only the age of the patient but also the race of the patient to interpret the serum PSA concentration. The clinical meaning of a given serum PSA value differs from one race to the next. The recent discovery of the different molecular forms of PSA and their potential ability to improve the diagnostic specificity of PSA is another significant step. Accordingly, the information about the relationship of age to the specific molecular forms and their ratios is a necessity. As urologists continue the quest for the ideal tumor marker for prostate cancer, utilizing age-specific reference ranges will continue to improve the clinical utility of the PSA test.
 ...
PMID:Age-specific reference ranges for serum prostate-specific antigen. 912 32

Jejunal folylpoly-gamma-glutamate carboxypeptidase hydrolyzes dietary folates prior to their intestinal absorption. The complete folylpoly-gamma-glutamate carboxypeptidase cDNA was isolated from a pig jejunal cDNA library using an amplified homologous probe incorporating primer sequences from prostate-specific membrane antigen, a protein capable of folate hydrolysis. The cDNA encodes a 751-amino acid polypeptide homologous to prostate-specific membrane antigen and rat brain N-acetylated alpha-linked acidic dipeptidase. PC3 transfectant membranes exhibited activities of folylpoly-gamma-carboxypeptidase and N-acetylated alpha-linked acidic dipeptidase, while immunoblots using monoclonal antibody to native folylpoly-gamma-glutamate carboxypeptidase identified a glycoprotein at 120 kDa and a polypeptide at 84 kDa. The kinetics of native folylpoly-gamma-carboxypeptidase were expressed in membranes of PC3 cells transfected with either pig folylpoly-gamma-carboxypeptidase or human prostate-specific membrane antigen. Folylpoly-gamma-carboxypeptidase transcripts were identified at 2.8 kilobase pairs in human and pig jejunum, human and rat brain, and human prostate cancer LNCaP cells. Thus, pig folylpoly-gamma-carboxypeptidase, rat N-acetylated alpha-linked acidic dipeptidase, and human prostate-specific membrane antigen appear to represent varied expressions of the same gene in different species and tissues. The discovery of the jejunal folylpoly-gamma-carboxypeptidase gene provides a framework for future studies on relationships among these proteins and on the molecular regulation of intestinal folate absorption.
 ...
PMID:Folylpoly-gamma-glutamate carboxypeptidase from pig jejunum. Molecular characterization and relation to glutamate carboxypeptidase II. 968 95

Cancer is consistently associated with anorexia. The Lobund-Wistar rat model of prostate cancer exhibits clinical manifestations (including anorexia) that resemble many aspects of the human disease. Cytokines are proposed to be involved in cancer-associated anorexia. Here we investigated mRNA profiles of feeding-modulatory cytokines and neuropeptides in specific brain regions of anorectic Lobund-Wistar rats bearing prostate adenocarcinoma tumor cells. Interleukin (IL)-1beta system components (ligand, signaling receptor, receptor accessory proteins, receptor antagonist), tumor necrosis factor-alpha, transforming growth factor-beta1, glycoprotein 130 (IL-6 receptor signal transducer), proopiomelanocortin (POMC, opioid peptide precursor), and neuropeptide Y (NPY) mRNAs were analyzed with sensitive and specific RNase protection assays. The same brain region sample was assayed for all components. The data show that early anorexia in tumor-bearing rats was associated with an upregulation of IL-1beta mRNA in the brain regions examined (cerebellum, cortex, and hypothalamus). IL-1 receptor antagonist (IL-1Ra) mRNA and IL-1 receptor type I mRNA levels were also significantly increased in the cortex and hypothalamus. All other cytokine components, POMC, or NPY mRNA levels were not significantly different between tumor-bearing and pair-fed (control) rats. IL-1beta mRNA and IL-1Ra mRNA were also significantly upregulated in the spleen of tumor-bearing rats. These data suggest that 1) IL-1beta mRNA upregulation in the brain may be relevant to the anorexia exhibited by the tumor-bearing Lobund-Wistar rat and 2) in vivo characterization of cytokine components in discrete brain regions during cancer is necessary to understand underlying molecular mechanisms responsible for cancer-associated neurological manifestations.
 ...
PMID:Brain cytokine mRNAs in anorectic rats bearing prostate adenocarcinoma tumor cells. 968 94


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