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)

We describe a new assay that is useful for identifying individuals who may be affected with Gaucher's disease. The assay involves the determination of serum acid phosphatase activity using the fluorogenic substrate 4-methylumbelliferyl phosphate. The assay measures acid phosphatase activity at pH 6.0 in the presence of 3.0 M 2-mercaptoethanol and requires a 5 microliter serum sample and a 15-min incubation period. Under these conditions, 2-mercaptoethanol preferentially inhibited the acid phosphatase activity in control serum but did not inhibit the elevated acid phosphatase present in the serum of patients with Gaucher's disease. Using this assay, we observed a 5-50-fold elevation in serum acid phosphatase activity in 8 patients with the adult, non-neuropathic form of Gaucher's disease when compared to control serum assayed under the same conditions. Serum from several heterozygotes free from pathology exhibited normal acid phosphatase activity when assayed at pH 6.0 in the presence of 2-mercaptoethanol. Acid phosphatase activity in serum from patients with prostatic cancer can be distinguished from that in Gaucher serum on the basis of the well-documented sensitivity of the former to inhibition by sodium tartrate. A serum sample from a patient with Niemann-Pick disease exhibited a mild elevation in tartrate-resistant acid phosphatase activity so that conclusive diagnosis of Gaucher's disease requires assaying leukocytes or fibroblasts from suspected patients for glucocerebroside:beta-glucosidase activity.
Clin Chim Acta 1977 Oct 01
PMID:Determination of serum acid phosphatase in Gaucher's disease using 4-methylumbelliferyl phosphate. 2 Feb 52

A brief description of physicochemical properties of the androgen receptors in the various target tissues is given. It is suggested that androgen receptors in all organs and species are very similar if not identical. It is also suggested that apparent differences in steroid binding are not due to differences in steroid specificity of receptors, but rather due to organ specific differences in target tissue metabolism. A short discussion of our studies on androgen receptors in the prostate, epididymis and testis of human being is also included. The properties of these receptors are similar, if not identical to those described in rats, and we have not been able to demonstrate differences in androgen receptors of non-neoplastic and neoplastic tissue. From studies on testosterone metabolism it is demonstrated that human prostate is metabolizing testosterone to DHT much faster than the seminal vesicles. Furthermore, there is a drastic reduction in DHT formation in tissue from prostatic cancer compared to normal and hyperplastic prostatic tissue.
Prog Clin Biol Res 1976
PMID:Androgen receptors in male sex tissues of rats and humans. 6 89

The effect of oestrogen (diethylstilboesterol diphosphate, DES-P) on immunity to tumour-associated antigens in patients with prostatic cancer was evaluated by leucocyte adherence inhibition, a suggested in vitro correlate of cellular immunity. Significant (P smaller than 0.05) suppression of immunity to malignant prostate was observed in thirty out of thirty-one patients following pre-incubation of their leucocytes with therapeutically significant levels of DES-P. Suppression of tumour-associated immunity by exogenous oestrogen provides further evidence to earlier studies demonstrating oestrogenic suppression of non-specific cellular responsiveness evaluated by mitogen-induced lymphocytic blastogenesis, and for concern over the efficacy of oestrogenic therapy and its adverse effect in the treatment of patients with hormone-dependent tumours and responsive diseases. The reduced efficiency of immunosurveillance of tumours and underlying infectious agents may contribute to the exacerbation of disease. While speculative, these observations may also be relevant to the possible assocition between uterine cancer and prolonged administration of DES and the development of vaginal tumours in offspring found in association with maternal ingestion during pregnancy.
Clin Exp Immunol 1979 Oct
PMID:Modulatory effects of oestrogen on immunological responsiveness. II. Suppression of tumour-associated immunity in patients with prostatic cancer. 9 29

Argyrophilia and argentaffinity, as basic properties of APUD cells, were investigated in 50 normal and hyperplastic prostates, which included both autopsy and surgical specimens from patients of various ages. Normal prostates (including glands from 3 foetuses) had 62% of argyrophil-positive granules in the glandular epithelia, while only 44% of the hyperplastic glands were positive. Argentaffin-positive cells were found in 12% of the surgical hyperplastic cases. Both argyrophil and argentaffin cells were distributed in zones, often in lobule-like shapes, lying along the basal membrane. On the basis of these findings, there is a discussion on the possible roles played by the so-called APUD cells in hyperplastic and neoplastic growths of the prostate, such as carcinoid tumours (apudomas) or endocrine-associated syndromes in the course of prostatic cancer.
Ric Clin Lab
PMID:APUD cells in normal and hyperplastic prostates. 9 88

The effect of flutamide on cortisol metabolism was studied in eight patients with prostate cancer. Flutamide markedly decreased the formation of 3 alpha, 17,21-trihydroxypregnane-11,20-dione (THF), and the 11-oxy-17-ketosteroid metabolites by 72%, 50%, and 46% respectively; however, 3 alpha, 11 beta, 17,21-tetrahydroxy-5 alpha- pregnan-20-one was increased by 46%. The 24-h mean plasma cortisol concentration was not altered. The cortisol production rate decreased by an average of 53% (from 32.7 to 15.5 mg/24 h). The effect of the drug on plasma cortisol kinetics was studied in three patients. This showed that flutamide increased the t1/2 (from 80 to 108 min) but decreased the distribution volume (from 17.8 to 13.8 liters) and the MCR (from 222 to 130 liters/24 h). The changes in THE and THF formation and in the t1/2 and MCR of [C]cortisol are similar to the effects observed in patients with intrahepatic cholestasis. It is suggested that in the case of flutamide these changes were also due to a cholestasis-producing effect of the drug on the liver. As the clinical response to the drug did not correlate with the cortisol metabolic changes, its therapeutic effect was probably not mediated by its effects on cortisol metabolism.
J Clin Endocrinol Metab 1978 Oct
PMID:Effect of flutamide on cortisol metabolism. 26 25

Acid phosphatase is a ubiquitous lysosomal enzyme that hydrolyses organic phosphates at an acid pH. Although the postpuberteral prostatic epithelial cell contains a uniquely high concentration of acid phosphatase, cellular components of bone, spleen, kidney, liver, intestine, and blood also contain this enzyme. The discovery that prostatic carcinoma cells often retain a high concentration of acid phosphatase characteristic of the normal postpubertal gland led to the recognition of the first clinically useful tumor marker. Recognition that the serum of patients with prostatic malignancy frequently contains an increased concentration of this enzyme has resulted in persistent efforts to identify the source, to accurately quantitate the level of serum acid phosphatase, and to determine the clinical significance of those levels. A variety of enzymatic and immunologic techniques have been employed to measure acid phosphatase. In the past, various substrates and inhibitors were utilized to increase specificity and sensitivity. Emphasis has now shifted to the development of radioimmunoassay and counterimmunoelectrophoresis in an attempt to enhance those parameters. Judgment of their efficacy awaits further testing and evaluation. The clinical significance of normal and abnormal serum acid phosphatase is constantly being reevaluated. In order to maximize the value of laboratory measurements, the clinical and pathologic status of the patient, the techniques employed in obtaining and storing the blood sample and the procedures used in analysis must be known and considered. Traditionally, the serum prostatic acid phosphatase has been thought to originate in the prostatic cancer cell and has been used to stage the disease. Until recently, elevated serum values have been accepted as an indication of extraprostatic disease, and were thought to rule out lesions confined to the prostate. The elevation of acid phosphatase levels in patients with disseminated disease or the failure of elevated levels to return to normal with treatment have been assumed to indicate a poor prognosis. However, unequivocal documentation of the validity of these statements is not available. Newer immunologic techniques for measuring acid phosphatase may significantly alter our current concept of its role as a tumor marker.
Urol Clin North Am 1979 Oct
PMID:Acid phosphatase. 38 94

An essential part of the classification of prostate carcinoma is the diagnosis of bone metastases. This was done with 70 patients using x-ray analysis, scintography, determination of the acid and alkaline phosphatase, and pelvic crest biopsy, as well as aspiration of the pelvic and sternal bone marrow. In addition, the hydroxyproline concentration was determined in the 24-hour-urine. The study, which was initially undertaken on a sample group (n = 145), yielded a high correlation between age and sex and hydroxyproline values. Women before menopause show significantly lower values than do men of the same age. The data on patients with prostata cancer (n = 70) showed that patients with and without bone metastases, who had been treated with estrogens, had a significantly lower quantity of hydroxyproline than did patients who had not received estrogen therapy. Patients with skeletal metastases (n = 24) showed significantly higher hydroxyproline excretion in the urine than did those with prostate cancer without metastases, or healthy men of the same age (n = 35). Comparison of the results of hydroxyproline determination with the other diagnostic methods for demonstrating bone metastases showed that hydroxyproline determination was diagnostically on par with the scintigram. Pelvic crest biopsy, pelvic and sternal marrow aspiration can be considered valuable supplementary diagnostic procedures.
Curr Probl Clin Biochem 1979
PMID:Urinary hydroxyproline in healthy patients and in prostate patients with and without bone metastases. 44 76

The effect of flutamide, a potent nonsteroidal antiandrogen, on the metabolism of iv tracers of [3H]estradiol was studied in five patients with advanced prostate cancer. The drug produced no change in the percentage of the injected radioactivity recovered in urine or in the glucuronide or nonglucuronide conjugate fractions. Of the five individual metabolites that were quantitated, estrone, estradiol, and estriol were unaffected by flutamide, but the drug caused striking decreases in conversion of estradiol to 2-hydroxyestrone (4.0% vs. 7.4%) (P less than 0.005) and 2-methoxyestrone (1.1% vs. 2.6%; P less than 0.05); every one of the patients showed a marked fall in recovery of both of these compounds. This depression of the formation of 2-oxygenated metabolites is reminiscent of the findings in liver disease; the same abnormality occurs regularly in cirrhosis and frequently in extrahepatic biliary obstruction. Taken together with our previous studies of the effects of flutamide on testosterone and cortisol metabolism, this study demonstrates that flutamide produces multiple functional, reversible, cirrhosis-like disturbances of steroid metabolism. Because these disturbances are universal in the patients studied regardless of whether they had clinical responses to flutamide, we doubt that the steroid metabolic changes play a role in the therapeutic effect of the drug.
J Clin Endocrinol Metab 1979 Sep
PMID:Effect of flutamide on estradiol metabolism. 46 81

Flutamide, a nonsteroidal antiandrogen, was given to 11 men with prostate cancer, in doses of 750 to 1500 mg daily for 0.5--7 months. Four patients had a clinical remission and seven showed no response. All the patients showed a profound change in the peripheral metabolism of testosterone: markedly increased conversion to androsterone (A) and correspondingly decreased conversion to etiocholanolone (E); the A/E ratio rose to levels never before observed consistently in any group of healthy or diseased humans. This change was probably due to alteration by flutamide of the relative activities of steroid 5alpha and 5beta reductase in favor of the former. 24-Hour mean plasma testosterone was increased in five of the six patients studied for this parameter, for the group as a whole, testosterone rose from 279 ng/dl to 484 ng/dl (P less than .05). 24-Hour mean values for plasma dihydrotestosterone, dehydroisoandrosterone, LH and FSH showed no significant change, for the group as a whole, in the same six patients. Since flutamide did not change the metabolic clearance rate or volume of distribution of testosterone tracers, the increased plasma levels of the hormone were probably due to increased production.
J Clin Endocrinol Metab 1977 Dec
PMID:The effect of flutamide on testosterone metabolism and the plasma levels of androgens and gonadotropins. 59 17

We evaluated counterimmunoelectrophoresis for use in measuring prostatic acid phosphatase in detection of prostatic cancer. After staining for acid phosphatase, we could detect as little as 0.3 ng of purified enzyme standard complexed with antibody by this technique. However, when serum samples were used as antigen, the method was less sensitive (1.5-2.0 ng) because some of the serum proteins migrate with the phosphatase and decrease the intensity of the stain for acid phosphatase. For this reason we could not detect the phosphatase in serum samples of normal persons; only patients with moderately (or greater) increased activity in their serum showed positive results. In contrast, by radioimmunoassay as little as 1.0 ng of the phosphatase can be detected in serum.
Clin Chem 1978 Jan
PMID:Counterimmunoelectrophoresis in determination of prostatic acid phosphatase in human serum. 61 43


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