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)

A solid-phase technique for radioimmunoassay of human prostatic acid phosphatase (EC 3.1.3.2) is described. Human prostatic acid phosphatase was purified from prostatic fluid. Monospecific antisera to the purified acid phosphatase were produced in rabbits. Disposable polypropylene tubes were coated with antiserum and used for radioimmunoassay with 125I-acid phosphatase. The nonspecific binding was minimized by saturating the binding sites of the tubes with bovine serum albumin. The working range of the technique was 1 to 30 ng of antigen. The solid-phase radioimmunoassay is rapid, sensitive, and efficient. In preliminary clinical trials it was shown that (a) patients with advanced prostatic cancer had elevated prostatic acid phosphatase levels by both enzymatic assay and radioimmunoassay assays, and (b) patients with other cancers were in the normal range for prostatic acid phosphatase.
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PMID:A solid-phase radioimmunoassay for human prostatic acid phosphatase. 117 Sep 44

We describe a modification of the Yang Pros-check radioimmunoassay for prostate-specific antigen (PSA) that increases the analytical sensitivity of the assay approximately threefold (from a working range of 0.3-50 to 0.1-1.2 micrograms/L). It can detect PSA added to zero-concentration diluent (bovine serum albumin solution) at 0.10 microgram/L or added to zero-concentration control female serum at 0.20 microgram/L (P less than 0.05). In 26 patients tested after cystoprostatectomy for bladder cancer (who had normal prostates without cancer on histologic examination), PSA values by this ultrasensitive assay were all less than 0.10 microgram/L. Therefore, we propose this value as the upper limit of the 95% reference interval. In a retrospective study of two patients who developed recurrent prostate cancer, serum PSA values increased above the 0.1 microgram/L detection limit 175 and 581 days before increasing above the 0.3 microgram/L detection limit of the standard Yang assay. This ultrasensitive radioimmunoassay of PSA should prove more useful than current methods for detecting early recurrence of prostate cancer.
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PMID:Ultrasensitive radioimmunoassay of prostate-specific antigen. 137 91

Basal serum levels and ACTH-induced increments ('delta-values') of dehydroepiandrosterone (DHA) and its sulfate (DHAS), 4-androstene-3,17-dione (A-4), 17 alpha-hydroxyprogesterone (17-OHP), cortisol and testosterone and serum albumin levels were studied in patients with prostatic cancer before treatment and after orchidectomy or during estrogen treatment (intramuscular polyestradiol phosphate during the first 3 months, followed by another 3 months with additional oral ethinyl estradiol). Orchidectomy as well as single drug intramuscular or oral + intramuscular estrogens exerted a similar suppressive effect on basal levels of A-4 and 17-OHP. Orchidectomy caused a slight decrease in basal DHAS, while combined oral + intramuscular estrogens caused a pronounced decrease in basal DHAS and also in DHA. Single drug intramuscular estrogens did not affect basal DHA or DHAS levels. Increased basal cortisol levels appeared during combined oral + intramuscular estrogen therapy. delta DHA and delta A-4 values were unaffected by endocrine treatment, but delta 17-OHP and delta cortisol increased slightly after orchidectomy and during estrogen therapy. Significantly decreased albumin levels were only observed during combined oral + intramuscular estrogen treatment. Determination of estriol, which is a major metabolite of estradiol originating from polyestradiol phosphate, revealed significantly higher estriol levels during combined oral + intramuscular estrogen treatment than during single drug intramuscular estrogen therapy, indicating an increased induction of hepatic 16 alpha-hydroxylase activity. The pronounced decreases in DHAS and also in DHA during combined oral + intramuscular estrogen treatment are probably another reflexion of the liver side effects of oral estrogens.
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PMID:Adrenocortical function in prostatic cancer patients: effects of orchidectomy or different modes of estrogen treatment on basal steroid levels and on the response to exogenous adrenocorticotropic hormone. 216 78

Peripheral serum levels of dehydroepiandrosterone (DHA) and its sulphate (DHAS), 4-androstene-3, 17-dione (A-4), 17 alpha-hydroxyprogesterone (17-OHP), cortisol and albumin were measured in patients with prostatic cancer before treatment and after orchidectomy or during combined oral and intramuscular oestrogen treatment. Orchidectomy caused a pronounced decrease in 17-OHP levels and minor but significant decreases in the levels of A-4 and DHAS. Dehydroepiandrosterone, cortisol and albumin were unaffected by treatment. Oestrogen treatment caused a pronounced decrease in the serum levels of DHA, DHAS, 17-OHP and A-4 and a small but significant decrease in serum albumin. Cortisol levels increased, probably due to elevated transcortin levels. The ratio of DHA to DHAS was unaffected by either orchidectomy or by oestrogen treatment. These results confirm that the testis contributes to circulating DHAS. The mechanism behind the more pronounced decrease in adrenal androgens during oestrogen treatment is not known but, for DHAS, increased metabolic clearance due to the decrease in albumin levels may contribute in this respect. The unchanged values for the ratio of DHA to DHAS indicate that this sex-specific sulphatase/sulphotransferase balance is insensitive to endocrine manipulations in adult men. The results further invalidate the hypothesis that there is a 'compensatory' increase in adrenal androgen output following orchidectomy.
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PMID:Orchidectomy or oestrogen treatment in prostatic cancer: effects on serum levels of adrenal androgens and related steroids. 295 20

A radioimmunoassay procedure for plasma 11-deoxycortisol (S) was developed using an antiserum prepared by immunizing rabbits with S-21-hemisuccinate bovine serum albumin and S-3-oxime-bovine serum albumin. Thereafter plasma S, cortisol (F) and adrenocorticotropic hormone (ACTH) responses to metyrapone were investigated in 13 normal adult males and 39 patients with prostatic cancer. The results were as follows: 1) The antiserum against S-3-oxime-bovine serum albumin had less cross reactivity (less than 10%) with other steroids than that against S-21-hemisuccinate bovine serum albumin and obtained a good standard curve. The intra-assay variance and interassay variance of this method using the former antiserum (N = 10) were 12.4% asd 14.9% respectively, and the blank value was 3.7 +/- 1.6 pg. 2) Basal levels of S. F and ACTH in plasma from 13 normal adult males, ranged 21 approximately 80 years, old, were 98.4 +/- 15.7 ng/dl (mean value +/- S.E.), 12.7 +/- 0.78 micrograms/dl and 30.6 +/- 3.02 pg/ml respectively. Those level increased to 7060 +/- 598 ng/dl, 24.3 +/- 1.69 micrograms/dl and 24.3 +/- 1.6 pg/ml at 9 a.m. following oral administration of metyrapone (30 mg/kg b.w.) at midnight. 3) Both basal levels and responses of plasma S and F to metyrapone increased remarkably, while those of ACTH were within the normal range in prostatic cancer patients during the estrogen therapy. It was considered that protein-bound S and F increased following elevation of corticosteroid binding globulin but returned to the normal range about 2 weeks after discontinuation of the therapy. 4) In case treated wih estrogens, plasma, S, F and AC normal range in prostatic cancer patients during the estrogen therapy. It was considered that protein-bound S and F increased following elevation of corticosteroid binding globulin but returned to the normal range about 2 weeks after discontinuation of the therapy. 4) In case treated wih estrogens, plasma, S, F and AC normal range in prostatic cancer patients during the estrogen therapy. It was considered that protein-bound S and F increased following elevation of corticosteroid binding globulin but returned to the normal range about 2 weeks after discontinuation of the therapy. 4) In case treated wih estrogens, plasma, S, F and ACTH responses to metyrapone were unchanged compared to normal adult males 2 approximately 4 weeks after discontinuation of the therapy, and this data suggested that estrogens had no inhibitory effect on the pituitary-adrenal axis. However, in cases treated with progestational agents over a long-term period, plasma S and ACTH responses to metyrapone decreased slightly but returned to the normal range 2 approximately 4 weeks after discontinuation of the therapy. This suggested that the inhibitory effect of these agents on the pituitary-adrenal axis was mild and reversible.
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PMID:[Plasma 11-deoxycortisol response to single dose metyrapone in prostatic cancer patients (author's transl)]. 626 18

The [3H]estramustine-binding macromolecule in human prostate was partially characterized using a number of chromatographic procedures. Although human estramustine-binding protein (HEMBP) had a marked tendency to aggregate in several systems, a molecular weight of about 54,000 was determined by gel filtration on Sephacryl S-200 Superfine and high-performance liquid chromatography. A sedimentation-coefficient of about 3.6S was obtained for HEMBP when analyzed by sucrose density gradient centrifugation. Isoelectric focusing in polyacrylamide gels indicated an isoelectric point of 4.7 to 4.8, which was in agreement with the elution position of HEMBP following chromatofocusing on Polybuffer Exchanger 94. Furthermore, HEMBP was eluted from diethylaminoethyl-Sepharose with 0.23 M KCl, was retained by concanavalin A-Sepharose (indicating that HEMBP is a glycoprotein), but did not interact with Affi-Gel Blue. Special efforts were concentrated on establishing that HEMBP was a species distinct from human serum albumin. Separation between the [3H]estramustine-labeled HEMBP and the [3H]estramustine-human serum albumin complex was obtained both on sucrose density gradients by chromatography on Affi-Gel Blue, by chromatofocusing, by gel filtration, by isoelectric focusing, and on concanavalin A-Sepharose by affinity chromatography. Twenty-two of 27 human benign hyperplastic prostate cytosol samples were found to contain protein immunochemically similar to estramustine-binding protein (EMBP) purified from rat ventral prostate as determined by the EMBP radioimmunoassay method. Concentrations from 0.2 to 139.6 ng EMBP per mg of total cytosolic protein (mean, 19.3) were determined. Furthermore, four of seven prostatic cancer specimens as well as two of two normal prostatic specimens were also found to contain rat EMBP-immunoreactive material. The unequivocal demonstration of the presence of a HEMBP is of great potential interest in consideration of estramustine phosphate (Estracyt) therapy against prostatic carcinoma. It is not inconceivable that the concentration of HEMBP in the carcinomatous tissue will be of significance in determining the drug uptake in the malignant tissue.
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PMID:Partial characterization and "quantitation" of a human prostatic estramustine-binding protein. 706 4

The 3-5 year survival rates of patients with disseminated Ewing's sarcoma (ES) or the closely related peripheral primitive neuroectodermal tumors (PNET) remain low, even under aggressive treatment involving highly toxic multidrug chemotherapeutic regimens. ES and PNET are sensitive to doxorubicin, but may escape treatment by expression of the multidrug-resistant phenotype and/or other mechanisms. In this study, we have identified albumin as growth supporting factor for ES and PNET cells in IGF-I-supplemented serum-free tissue culture medium. To investigate the specificity and toxicity of albumin-based drug conjugates, doxorubicin was coupled to bovine serum albumin (BSA) by either a two step glutaraldehyde or carbodiimide-C4-spacer technique, yielding monomeric DOX-albumin conjugates with conjugation numbers ranging from 3-20 moles DOX/mole BSA. Cellular uptake of fluorescein-isothiocyanate-(FITC)-labeled albumin and DOX-albumin conjugates could be demonstrated by flow cytometric measurements of cell-associated fluorescence and confocal microscopy. The cytostatic activity of these conjugates against ES/PNET cell lines, a neuroblastoma (LAN-1) and prostate cancer carcinoma cell line (PC-3) and normal lymphoblasts was tested in short-term proliferation assays (48 h). The results show a high selectivity of the DOX-albumin conjugates for ES/PNET cell lines, with highest growth inhibition by conjugates with low DOX conjugation numbers (n = 3) in serum-supplemented medium (17-32 fold loss of activity compared to free DOX), followed by 20-DOX-C4-albumin in serum-free medium and low activity of the other conjugates. In conclusion, DOX-albumin conjugates inhibit the growth of ES/PNET cell lines selectively, showing low activity against the unrelated carcinoma line PC-3 and sparing normal lymphoblasts. The inverse correlation of activity and conjugation number demonstrates a low cytotoxic activity of DOX in acid-stable binding to monomeric albumin, pointing to a selective cytostatic activity of the modified albumin against ES and PNET cells, even in the presence of a 100 fold excess of unmodified serum albumin.
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PMID:In vitro antiproliferative effects of albumin-doxorubicin conjugates against Ewing's sarcoma and peripheral neuroectodermal tumor cells. 784 32

We have established a procedure for the production of milligrams of free PSA (fPSA) from LNCaP cells derived from a human carcinoma of the prostate. By growing LNCaP cells in a serum-free medium in the presence of a synthetic androgen (R1881) and taking advantage of the special design of the Micro-mouse Hollow Fiber Bioreactor, relatively pure fPSA could be obtained. We found that columns containing either Sephacryl S-100 or S-200 could be used to remove the small amount of bovine serum albumin (BSA) and PSA-alpha 1-antichymotrypsin complex (PSA-ACT) from the preparation. More than 90% of the PSA from LNCaP cell cultures are fPSA. Like fPSA from seminal plasma, two fractions of fPSA differing in protease activity can be separated by DEAE-Sepharose chromatography. Based on the band pattern exhibited on the Western blot following sodium dodecyl sulfate-polyacrylamide electrophoresis separation, fPSA from LNCaP contains more inactive PSA isoforms. This was confirmed by chromatofocusing: the isoelectric point (pl) of the major PSA isoforms from the LNCaP cell culture were higher (6.8 and 6.6) than that (6.4 and 6.1) of fPSA from seminal fluid. We conclude that the LNCaP cell culture is a reliable source for obtaining large quantities of pure fPSA both for the preparation of assay calibrators and controls and for studying the difference in fPSA between benign prostate disease and prostate cancer.
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PMID:Production of milligram concentrations of free prostate specific antigen (fPSA) from LNCaP cell culture: difference between fPSA from LNCaP cell and seminal plasma. 948 63

Various prognostic factors for survival have been identified in patients with colorectal cancer. However, although it has been suggested that the pre-treatment serum albumin concentration is a prognostic indicator in certain malignant diseases (melanoma, prostate cancer, leukaemia), its value in patients with colorectal cancer remains unclear. This study investigated the prognostic value of serum albumin in this patient group. A total of 431 patients presenting to the Professorial Surgical Unit between 1972 and 1985 were analysed in this study. Using the Cox proportional hazard model, age, tumour stage (Dukes' stage) and tumour differentiation were shown to be independent prognostic factors for survival in patients with localized colorectal cancer. In addition, the pre-treatment serum albumin concentration was found to be an independent prognostic indicator. This is the first such documentation for patients with 'curable' colorectal cancer.
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PMID:Serum albumin: a prognostic indicator in patients with colorectal cancer. 965 76

The present study was undertaken to evaluate the relationship between serum tumor necrosis factor (TNF) and cachexia in patients with prostate cancer. TNF levels were determined in 110 serum samples from prostate cancer patients by an enzyme immunoassay. Serum TNF activity was positive in 76% of the patients with relapsed disease, whereas only 11% of the untreated patients and 0% of the patients in remission as a result of endocrine therapy were positive. The serum total protein and albumin levels, hemoglobin levels, and body mass index of the patients with elevated serum TNF levels were significantly lower (P < 0.05) than the corresponding values in patients with undetectable serum TNF levels. The serum TNF levels of patients with serum albumin levels of <3.5 g/dl, serum total protein levels of <7.0 g/dl, hemoglobin levels of <11.0 g/dl, and a body mass index of <21 kg/m2 were significantly higher (P < 0.05) than the values in their respective counterparts. There was a significant correlation between the detectability of serum TNF and performance status (P < 0.05). Patients with elevated serum TNF levels had a significantly higher mortality rate (P < 0.05) than those with undetectable serum TNF levels. These findings suggest that TNF may be one of the factors contributing to the complex syndrome of cachexia in patients with prostate cancer.
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PMID:Association between tumor necrosis factor in serum and cachexia in patients with prostate cancer. 967 50


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