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.
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PMID:Determination of serum acid phosphatase in Gaucher's disease using 4-methylumbelliferyl phosphate. 2 Feb 52

In the 36 months since its inception, the National Prostatic Cancer Project treatment subgroup has randomly assigned over 360 patients with progressive advanced prostatic cancer who were no longer responsive to endocrine manipulation to either one of four different clinical studies. The initial study demonstrated a clear superiority for 5-fluorouracil (5-FU) and cyclophosphamide over continued conventional therapy. Beneficial responses were documented and are associated with increased survival rates and relief from pain and other symptoms. A proportionately larger number of patients obtained clinical benefit (stable and partial regression) on cyclophosphamide than on standard or 5-FU therapy. The criteria for evaluation of patients are supported by the survival data, ie, responders have survived for a longer period of time than those patients who continued in progression. Preliminary data from the subsequent protocols have documented a 30% response (stable and partial regression) in patients receiving oral estramustine phosphate and definite responses in patients treated with DTIC; Too few patients have been treated with Leo 1031 to offer total response rates at this time, although the early results are promising. These clinical studies have firmly established a place for chemotherapy in the management of prostatic cancer. New trials will introduce single- and multiple-drug chemotherapy at earlier phases of the clinical course of prostatic cancer patients.
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PMID:National randomized study of chemotherapeutic agents in advanced prostatic carcinoma: a progress report. 14 26

30 patients with oestrogen-escaped carcinoma of the prostate have been treated with estramustine phosphate (Estracyt). 27% showed a partial objective response and 33% had a subjective response. The terms used for defining a response are challenged and it is recommended that comparative controlled trials are necessary to judge the place of this drug in the management of advanced prostatic cancer.
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PMID:The treatment of oestrogen-escaped carcinoma of the prostate with estramustine phosphate. 33 86

The relationship of prior hormonal therapy to subsequent response on estramustine phosphate (Estracyt) was examined in 107 patients with advanced prostatic cancer treated in two different Phase II chemotherapy trials. In both trials patients with the longest prior hormonal treatment were the least likely to respond to estramustine phosphate. Patients in the series from the National Prostatic Cancer Project with a response classification to prior hormonal therapy had only a 26 per cent response to subsequent estramustine phosphate therapy, whereas 40 per cent of those with no prior response to hormonal therapy responded to estramustine phosphate. This latter group had the shortest average disease duration from diagnosis. The sample of prostate cancers studied appeared to include groups that were sensitive to both hormones and cytotoxic activity as well as to either of these two alone. These data support the contention that estramustine phosphate may act both as an estrogenic and a cytotoxic agent.
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PMID:Relationship of prior hormonal therapy to subsequent estramustine phosphate treatment in advanced prostatic cancer. 39 Aug 10

40 patients with inoperable, histologically proved carcinoma of the prostate were treated with estramustine phosphate. 35 patients had progressive, symptomatic, metastatic disease unresponsive to conventional oestrogens and/or castration Estramustine phosphate was given intravenously initially at a dose of 150 mg/day increasing to 300 mg/day. After 3 weeks or more oral therapy was substituted in 23 patients at a dose of 560 mg/day. Of 23 evaluable patients given the drug by both routes, 17 died after a mean treatment period of 12.5 months and 6 are alive and well after a mean treatment period of 27.7 months. The cause of death in 2 patients was probably, and in a third certainly, due to myocardial infarction. The other 31 deaths were due to carcinoma of the prostate. 18 patients showed transient toxic side-effects. No haematological abnormalities were found during treatment. An attempt at active treatment with estramustine phosphate in patients with prostatic cancer is justified when the disease is resistant to treatment with conventional oestrogens.
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PMID:Treatment of advanced carcinoma of the prostate with estramustine phosphate. 83 52

We treated 21 patients with stage D prostatic adenocarcinoma who had had unsuccessful hormonal therapy with a combination of 600 mg. per M.2 per day estramustine phosphate (Estracyt) and 15 mg. per M.2 per day prednimustine (Stereocyt, Leo 1031) in daily oral doses. Estramustine is a combination of estradiol and nitrogen mustard, and alone has shown objective responses in advanced prostatic cancer. Prednimustine is an ester of chlorambucil and prednisone. The preliminary results (after 2 to 9 months of therapy) show 5 patients (24 per cent) did not benefit from the drug and 7 patients (33 per cent) are stable. These preliminary results indicate the possible advantage of adding an alkylating agent (prednimustine) to estramustine in advanced prostatic carcinoma. Currently, a national randomized trial by the National Prostatic Cancer Project is evaluating this therapeutic innovation.
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PMID:Combined therapy of advanced prostatic carcinoma with estramustine and prednimustine. 83 97

I describe a simple, rapid ion-exchange column-chromatographic technique for separating the acid phosphatase (EC 3.1.3.2) isoenzymes in human serum and tissue. Extracts of platelets, spleen, liver, erythrocytes, and prostate were used to determine optimum conditions for separating these isoenzymes. Samples layered on mini-colunms of DEAE-Sephadex A-50 were eluted stepwise with sodium chloride (100, 200, and 300 mmol/liter, buffered with tris (hydroxymethyl)aminomethane). Activity in column effluents was measured with p-nitrophenol phosphate as substrate, and their isoenzyme content was assessed by electrophoresis on polyacrylamide gel. Comparision of activity patterns so derived for various tissues revealed prostatic tissue to be a rich source of acid phosphatase isoenzyme 2 activity. Evaluation of sera from six patients with prostatic cancer revealed isoenzyme patterns with prominent amount of isoenzyme 2 (3.8 to 27.6 U/liter). sera from 10 healthy laboratory technicians contained isoenzyme 2 in the range of 0.3-0.5 U/liter. Samples from two patients with abnormally high activity owing to nonprostatic conditions (Gaucher's disease and carcinoma of lung) exhibited less than 2 U of isoenzyme 2 per liter and acid phosphatase isoenzymes 3-5 that were 50- to 100-fold the normal range. Quantification of isoenzyme 2 by DEAE-Sephadex column chromatography as described appears to provide a more sensitive and specific approach to diagnosis of prostatic cancer.
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PMID:Separation of tissue and serum acid phosphatase isoenzymes by ion-exchange column chromatography. 84 61

Estramustine phosphate is a nitrogen mustard derivative of estradiol that has been advocated for the treatment of prostatic cancer. The compound was designed with the hope that the estrogen moiety would direct the alkylating moiety to estrogen-dependent malignancies, where the alkylating moiety would be released specifically. Preclinical and clinical data are reviewed to determine to what extent that challenging concept is fulfilled. In addition, we have examined critically the efficacy of this drug for the treatment of prostatic cancer. From available data it appears that there is no evidence that the alkylating moiety of estramustine phosphate is specifically freed in estrogen-dependent tissues. Estramustine phosphate appears to be an active compound with acceptable toxicity in prostatic cancer. However, further clinical trials must be undertaken to clarify the future role of estramustine phosphate in the treatment of prostatic cancer.
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PMID:Estramustine phosphate: a specific chemotherapeutic agent?. 85 Mar 19

The authors have evaluated a new kinetic acid phosphatase method in which the substrate is alpha-naphthyl phosphate. The original claim that this substrate was highly specific for the prostatic isozyme has been strongly challenged. Therefore, large numbers of patients in the following groupings were included in the evaluation: 52 urology clinic patients, 17 patients with uremia, 11 patients with multiple myeloma and 231 patients who had undergone prostatic biopsies. Two hundred seventy of these patients were found to be free of prostatic cancer. Of these, seven had acid phosphatase values above the upper limit of normal. Five of these seven patients had diagnoses of fibromuscular glandular hyperplasia. One was a woman who had multiple myeloma, and one was a uremic patient. Fifteen of 17 patients who had metastatic cancer of the prostate had elevated acid phosphatase activities, whereas one of 24 patients who had cancer of the prostate but no evidence of metastases had an elevated value.
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PMID:An evaluation of a kinetic acid phosphatase method. 86 5

The Dunning R3327H rat prostatic adenocarcinoma appears to be an appropriate animal model for studying prostatic cancer. This report contains a detailed characterization of this tumor at the morphologic, biochemical, and therapeutic levels. Electron micrographic, histologic, and histochemical studies clearly establish the adenocarcinoma nature of this tumor. The histology of the R3327H tumor is similar to well-differentiated human prostatic cancer. The biochemical and enzymatic profile of the tumor indicates its origin from the rat dorsolateral prostate. The cell kinetics and growth rates of this tumor following a variety of hormonal manipulations (castration, estrogens, androgens, and antiandrogens) have established that 70%-90% of the cells in this tumor require androgens for their growth. However, 10%-30% of the cells are capable of growth in the absence of androgens. Both cell types are present in the initial tumor inoculum and these different cell types possess similar growth rates. The predominance of the androgen-sensitive cells accounts for the relatively greater size of the tumor achieved in the intact male animal at a given growth time. After the tumor is well established in an intact animal, subsequent estrogen therapy or castration resulted in a marked diminution in tumro volume. This was followed by a subsequent relapse. In addition, estramustine phosphate was also shown to cause shrinkage in the tumor volume.
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PMID:Characterization of the Dunning R3327H prostatic adenocarcinoma: an appropriate animal model for prostatic cancer. 87 32


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