UMLS:C0376358 - FACTA Search

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Query: UMLS:C0376358 (prostate cancer)
59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Expression of the prostate-specific membrane antigen. 751 Oct 53

Prostate-specific antigen (PSA) is a well-characterized human prostate-specific glycoprotein. PSA has been shown to be the most effective immunohistologic marker for prostate cancer, as well as the most useful serologic test in staging and monitoring prostate cancer and in early detection of recurrent disease. The greatest clinical value of PSA is an aid for early detection of prostate cancer. Recent studies have indicated that PSA-based screening of the older population for organ-confined early-stage prostate cancer is an acceptable, practical, and reliable modality. The accuracy of PSA screening is within the same range as the mammogram. The cost-effectiveness of PSA is comparable to other cancer screening tests. Although the increase in the patient's survival due to PSA-based detection of early prostate cancer remains to be documented, it is generally agreed that the PSA test along with digital rectal examination (DRE) should be included in the annual physical examination for men 50 years of age or older. High-risk men are urged to commence at age 40. Asymptomatic men who have both a negative DRE and normal PSA blood test need only to continue an annual DRE and PSA check-up. Men who have a negative DRE and elevated PSA, and all those who have a suspicious DRE regardless of PSA results, should undergo further diagnostic workup, such as transrectal ultrasonography with biopsy of visible lesions. The cure rate is high with timely treatment, when prostate cancer is detected while still confined to the prostate.
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PMID:Prostate-specific antigen in screening of prostate cancer. 752 95

PSA is a 34-kDa 240-amino-acid glycoprotein produced exclusively by prostatic epithelial cells. PSA is a serine protease, is a member of the kallikrein gene family, and has a high sequence homology with human glandular kallikrein. It has chymotrypsin-, trypsin-, and esterase-like activities. In the serum it is present mainly in a complex form with alpha 1-antichymotrypsin. It is secreted in the seminal plasma and is responsible for liquefaction of the seminal coagulum. The production of PSA proteins appears to be under the control of circulating androgens acting through the androgen receptors. The PSA gene is up-regulated predominantly by androgens at both the protein and mRNA levels. DRE causes minimal changes in the PSA level, while prostate massage, ultrasonography, systoscopic examination, and prostate biopsy can all cause clinically significant elevations. Other conditions, such as prostatitis, prostate intraepithelial neoplasia, acute urinary retention, and renal failure can also elevate the PSA level. The value of PSA as a screening tool is questionable because of the great deal of overlap in PSA levels between BPH and prostate cancer. However, if used in men over 50, in conjunction with DRE and/or ultrasonography, it may become a vital part of the early detection program. PSA's role in determining the clinical and pathological stage is also limited, in spite of the direct correlation between the pathological stage and the PSA level, because of great overlap in the PSA levels in various stages. The most important clinical utility of PSA is in monitoring patients after definitive therapy. PSA is most sensitive and reliable in the detection of a residual tumor, possibly recurrence, or disease progression following treatment, irrespective of the treatment modality. PSA can accurately predict the tumor status and can detect recurrence several months before its detection by any other method. PSA is also a very sensitive and specific immunohistochemical marker for tumors of prostatic origin. Compared to PAP, PSA is a more precise and meaningful marker in all clinical situations. With the development of ultrasensitive assays and the adoption of an international standard PSA calibrator, so that results from multicenter studies can be compared, PSA could become one of the most useful tumor marker in cancer biology.
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PMID:Prostatic specific antigen. 753 74

Monoclonal antibodies CC49 and B72.3, which recognize a tumor associated glycoprotein (TAG-72) related to sialyted Tn antigen, have been used in clinical trials for radionuclide imaging, and treatment of colon, breast and ovarian carcinoma. In addition, studies with CC49 in patients with metastatic hormone refractory prostate cancer have been initiated based on the observed expression of TAG-72 in primary prostate cancer. We examined whether TAG-72 expression is a common feature of primary, metastatic and hormonally treated prostatic carcinoma. Immunohistochemical analysis of 25 primary prostatic carcinomas confirmed previous data that 21 of 25 specimens (80%) were immunoreactive with CC49. CC49 staining was noted in all 6 well (Gleason score 2 to 4), 8 of 10 moderately (Gleason score 5 to 6) and 7 of 9 poorly (Gleason score 7 to 9) differentiated tumors. CC49 immunoreactivity was noted in 10 of 20 hormonally treated prostate cancers and in 21 of 25 tumors without hormonal therapy. Intense CC49 staining of prostatic intraepithelial neoplasia was present in all 5 specimens examined. In contrast to the primary lesion, many metastatic prostate cancers lacked detectable CC49 immunoreactivity. Of 24 pelvic lymph node metastases from different patients only 4 (17%) had significant CC49 staining and 5 others had rare CC49 positive cells. However, 6 of 12 bone metastases showed CC49 immune staining. One specimen from an anaplastic locally recurrent tumor showed no reactivity. To our knowledge we present the first analysis of TAG-72 expression in a large series of patients with hormonally treated and metastatic prostate cancer, the most likely candidates for CC49 immunotherapy. Our findings that lymph node and bone metastases from prostate cancer are less likely to express significant amounts of TAG-72 than primary prostate cancer suggest that pretreatment biopsy typing for TAG-72 may be necessary to optimize the results of ongoing CC49 imaging and therapy studies.
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PMID:TAG-72 expression in primary, metastatic and hormonally treated prostate cancer as defined by monoclonal antibody CC49. 771 79

Without question, much has been learned about the glycoprotein PSA in recent years. By increasing our understanding of this tumor marker's biochemical and physiologic properties, we will be able to improve its clinical utility. The discovery of the various molecular forms of PSA represents a significant advancement. Knowing the concentration and ratio of these PSA forms will be valuable in deciding which patients require further evaluation with transrectal ultrasound and prostate biopsy and which men can be monitored safely without undergoing further invasive testing. This information will be most valuable in treating the patient with a mildly elevated serum PSA level. Although assays are not yet available to detect specifically hK2, the striking similarities of hK2 to PSA, including selective expression in the prostate, suggest that this marker may also prove useful in prostate cancer management. Indeed, a new era of PSA testing has been entered, and the entire field of prostate cancer will benefit.
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PMID:Molecular forms of prostate-specific antigen and the human kallikrein gene family: a new era. 753 36

Prostate-specific antigen (PSA) is a tissue-specific serine protease similar in structure to the trypsin-like glandular kallikreins but which is unique inasmuch as the enzyme activity is similar to that of chymotrypsin. The active enzyme is a single chain glycoprotein of 237 amino acids. The major form of PSA in serum is complexed to alpha 1-antichymotrypsin (ACT). A small amount is free, non-complexed despite a large excess of ACT. This suggests that the form in serum lacks enzyme activity. Although serum PSA concentrations are regularly abnormally high (above 4 micrograms/L) in prostate cancer (CAP), the utility of PSA measurements in the early detection of CAP is limited, as many tumors are undetected at a cut-off of 4 micrograms/L. Also, 25% of all men with benign prostate hyperplasia (BPH) have serum PSA levels above 4 micrograms/L. Using assays specially developed to measure free and complexed forms of PSA in serum, we found the proportion of PSA-ACT complexes to be higher in CAP than in BPH, but the ratio of free-to-total PSA in serum to be lower. Using an abnormally low ratio of free-to-total PSA to detect CAP increases diagnostic specificity by 15 to 20%, compared to using a high serum PSA concentration. This suggests that the ratios of free-to-total PSA significantly increase the ability to distinguish BPH from localized CAP. The molecular basis is unclear, but may be related to the high incidence of prostate tumor cells producing both PSA and ACT. This is in contrast to the lack of ACT production in BPH epithelium. Possibly owing to lack of ACT production in BPH areas, conditions are not optimal for complex formation, whereas tumors producing both ACT and PSA may promote the formation of PSA-ACT complexes in CAP.
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PMID:Regulation of the enzymatic activity of prostate-specific antigen and its reactions with extracellular protease inhibitors in prostate cancer. 754 78

Human prostate-specific antigen (PSA), a 33- to 34-kDa serine proteinase with extensive homology to glandular kallikrein, is a single-chain glycoprotein that contains 7% carbohydrate. The presence of PSA in the serum of patients with prostatic cancer is widely employed as a marker of disease status. PSA has also been thought of as a possible target for use in active specific immunotherapy protocols. To date, the source of PSA employed has been seminal fluid from different individuals; this has raised concerns about differences among PSA batches for standardization of assays. This report is the first description of the production and the purification of a recombinant source of PSA using a baculovirus expression system. A baculovirus recombinant of the cDNA encoding the full length PSA was expressed in insect cells yielding two major immunoreactive products of 31 and 29 kDa. The latter size conforms to the molecular weight of a core preprotein deduced from the sequence of the cDNA insert. The larger protein represents the N-linked glycosylated form of the preprotein. Western blot analysis showed that both the glycosylated and aglycosylated forms of PSA reacted with a polyclonal and two different monoclonal antibodies specific for PSA. bV-PSA, like commercially available PSA, showed also low-molecular-weight immunoreactive products when culture supernatants were concentrated or taken through steps of purification. bV-PSA was purified to a final product consisting of a major 29-kDa protein and a minor 31-kDa protein.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Generation, purification, and characterization of a recombinant source of human prostate-specific antigen. 756 44

Prostate-specific membrane antigen (PSM) is a glycoprotein recognised by the prostate-specific monoclonal antibody 7E11-C5, which was raised against the human prostatic carcinoma cell line LNCaP. A cDNA clone for PSM has been described. PSM is of clinical importance for a number of reasons. Radiolabelled antibody is being evaluated both as an imaging agent and as an immunotherapeutic in prostate cancer. Use of the PSM promoter has been advocated for gene therapy applications to drive prostate-specific gene expression. Although PSM is expressed in normal prostate as well as in primary and secondary prostatic carcinoma, different splice variants in malignant tissue afford the prospect of developing reverse transcription-polymerase chain reaction (RT-PCR)-based diagnostic screens for the presence of prostatic carcinoma cells in the circulation. We have undertaken characterisation of the gene for PSM in view of the protein's interesting characteristics. Unexpectedly, we have found that there are other sequences apparently related to PSM in the human genome and that PSM genomic clones map to two separate and distinct loci on human chromosome 11. Investigation of the function of putative PSM-related genes will be necessary to enable us to define fully the role of PSM itself in the development of prostatic carcinoma and in the clinical management of this malignancy.
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PMID:Prostate-specific membrane antigen: evidence for the existence of a second related human gene. 766 65

Prostate-specific antigen (PSA) is a glycoprotein produced exclusively by prostatic tissue. PSA's absolute tissue specificity makes it valuable as a forensic marker and, more important, as a tumor marker for prostatic cancer. Prostatic cancer is prevalent in the older male population and is a major cause of death in men. Previously, prostatic acid phosphatase (PAP) was used to help diagnose and monitor the efficacy of therapy for prostate cancer. PAP has now been displaced by PSA, which has greater clinical sensitivity even though it has less clinical specificity. PSA is useful for monitoring therapy, particularly surgical prostatectomy, because complete removal of the prostate gland should result in PSA being undetectable. Measurable PSA after radical prostatectomy indicates residual prostatic tissue or metastasis, and increasing PSA concentrations indicate recurrent disease. PSA is also useful for screening selected populations of patients with symptoms indicative of prostate cancer; its use for general screening is debatable because of its less-than-optimal specificity, the cost of unselected screening, and the lack of evidence that early detection of prostate cancer decreases morbidity and mortality. Distinguishing between patients with prostatic cancer and those with benign prostatic hypertrophy is particularly difficult because of the overlap in PSA values in the two groups. Determining the rate of change in PSA per year from serial measurements or calculating the ratio of PSA per volume of the prostate gland may allow these two groups to be more readily differentiated.
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PMID:Prostate-specific antigen: biochemistry, analytical methods, and clinical application. 769 Jun 91

The prostate-specific antigen (PSA) is a glycoprotein synthesized exclusively by the prostate. Since manipulations on the prostate can increase PSA serum levels, we investigated the effects of transrectal hyperthermia on PSA levels in prostate cancer (PC) and benign prostatic hyperplasia (BPH). Patients and treatments were the following: group 1a, PC St.D (n = 12): 8 hyperthermia sessions (twice a week) and LHRH-agonists plus flutamide; group 1b, PC St.D (hormone resistant; n = 10): 8 hyperthermia sessions (once a week) and epirubicin (50 mg intravenously, once a week); group 1c, PC St.C (n = 5): 6 hyperthermia sessions (once a week) and radiotherapy (60 Gy); group 2, BPH (n = 10): 8 sessions (twice a week). PSA levels were determined before, during (immediately before each hyperthermia session) and 1 week after therapy. Apart from hormone-/hyperthermia-treated patients, who showed a continuous decrease in PSA during therapy, all the other groups revealed a transient increase in PSA during the hyperthermia treatment. This effect is attributed to manipulations on the prostate and hyperthermia-specific effects on prostatic cells. The decrease in PSA on hormone/hyperthermia therapy can be explained by the tremendous effect of androgen deprivation on PSA levels overshadowing the hyperthermia effect.
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PMID:Influence of transrectal hyperthermia on prostate-specific antigen in prostatic cancer and benign prostatic hyperplasia. 768 98

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