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)

Ten patients with previously untreated prostatic carcinoma were studied to evaluate the hormonal effects of different doses of estramustine phosphate (Estracyt). The drug was given by mouth in increasing doses; during the first month 70 mg daily, during the second 140 mg, during the third 280 mg and during the fourth and following months 560 mg. The following hormonal parameters were studied before the treatment and then once weekly during a period of four months: testosterone, dihydrotestosterone, androstenedione, cortisol, FSH and LH. The levels of the steroids were also re-assessed one to two years later. The patients were also followed clinically at regular intervals. Initial testosterone levels of approximately 20 nmol/l plasma were reduced to approximately 0.6 nmol/l already by the lowest Estracyt dose of 70 mg/day. No further decrease was obtained by a stepwise increase of doses up to 560 mg/day. The plasma levels of dihydrotestosterone, androstenedione, FSH and LH were also reduced significantly following the administration of the lowest daily Estracyt dose and then remained at that low level. Cortisol levels increased steadily during the four months of the study. After longterm treatment the hormonal indices were by and large the same as during the last initial treatment period. Initially, the clinical effect of the treatment was excellent. In 4 patients, however, the therapy had to be discontinued after some time, because of complicating oedema (2 patients) or refractoriness to therapy (2 patients). Three years after initiating the therapy 6 patients still were on Estracyt treatment. All of them were doing well subjectively. In 5 patients the prostatic cancer was in remission or at least stable. In one patient, however, skeletal metastases were progressing. In conclusion, Estracyt was found to possess a maximal hormonal (oestrogenic) effect already in doses far below those usually recommended.
 ...
PMID:Hormonal effects of different doses of estramustine phosphate (Estracyt) in patients with prostatic carcinoma. 678 1

Two hundred and twelve patients treated for prostatic cancer grade I or II were investigated for cardiovascular complications. The patients were part of a multicentre study in the Stockholm area and had been randomized to treatment with either estramustine phosphate (Estracyt) or polyestradiol phosphate and ethinyl estradiol. Cardiovascular complications categorized as impaired arterial circulation including ischemic heart disease, venous thromboembolism, cardiac incompensation and cerebral depression were found to be equally frequent following the two different forms of treatment. Among the patients getting cardiovascular complications, these occurred within two months after the start of treatment in 50% and within one year in 85% of them. There was a statistically significant correlation between the incidence of cardiovascular complications and a history of previous cardiovascular disease. This criterion was however in retrospect found to predict cardiovascular complications in only 67 of the 126 patients getting one or several of these complications.
 ...
PMID:Cardiovascular complications to treatment of prostate cancer with estramustine phosphate (Estracyt) or conventional estrogen. A follow-up of 212 randomized patients. 693 12

Two parallel prospective randomized studies have been undertaken by the EORTC Urological Group in previously untreated patients with prostatic cancer in order to compare low dose Stilboestrol versus Cyproterone acetate versus Medroxyprogesterone acetate in the first trial, and Stilboestrol versus Estracyt in the second trial. Although the follow up is still short, no superiority of the other drugs over Stilboestrol had appeared so far with regard to either objective response or significant side effects apart from gynaecomastia. In the third trial, patients with advanced disease no longer responsive to hormonal treatment were randomized to either Adriamycin or Procarbazine. Toxicity and early death were particularly frequent in Procarbazine treated patients, whereas most patients progressed in both treatment groups.
 ...
PMID:EORTC protocols in prostatic cancer. An interim report. 693 20

To clarify the mechanism of action of Estracyt, we performed experiments using 3H-estramustine of high specific activity. 3H-Radioactivity accumulated selectively in the ventral prostate of castrated male rats after the administration of 3H-estramustine. Estramustine and its metabolites were retained in the ventral prostate for long time periods. The uptake of 3H-radioactivity was almost totally localized in the cytosol fraction, but not in a purified receptor fraction. The apparent equilibrium dissociation constant of the estramustine binding protein was 18.9 nM, and the apparent equilibrium Bmax value was 0.76 nmoles/mg of cytosol protein. In addition, we wish to report in this paper the results of clinical trials of Estracyt studied by a cooperative research group in Japan from 1977 to 1979. It was concluded that Estracyt was effective in 89% of previously untreated prostatic cancer patients and in 38% of reactivated cancer patients.
 ...
PMID:Mechanism of retention of estramustine in the rat prostate and results of a clinical trial of Estracyt in Japan. 704 23

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.
 ...
PMID:Partial characterization and "quantitation" of a human prostatic estramustine-binding protein. 706 4

Plasma samples from patients with prostatic cancer under oral treatment with estramustine phosphate (Estracyt) were quantitatively analyzed for the presence of the parent drug and some of its possible metabolites. Specific methods based on radioimmunoassay and gas chromatography-mass fragmentography were used. Dephosphorylation and oxidation at the 17-position of estradiol were shown to be the major metabolic routes. The estrone analogue of estramustine was found to be the main metabolite in plasma. Elevated levels of estradiol and estrone showed that hydrolysis of the carbamic ester also occurred in these patients. Their estrogen levels were compared with those of another group of prostatic cancer patients receiving conventional hormonal therapy, polyestradiol phosphate (Estradurin). Similar concentrations of estradiol were found in the two groups but the concentrations of estrone were higher in patients given estramustine phosphate.
 ...
PMID:Metabolism of estramustine phosphate (Estracyt) in patients with prostatic carcinoma. 727 9

The following endocrine treatment modalities have been used in advanced prostatic carcinoma: 1. orchiectomy plus estrogens; 2. primary orchiectomy with delayed estrogen employment; 3. initial estrogen therapy with delayed orchiectomy; 4. initial cyproterone acetate or medroxyprogesterone acetate; 5. a combination treatment: estramustine phosphate, cyproterone acetate or estrogens plus bromocriptine. The application of phase-III studies permits the subsequent conclusions: Simultaneous orchiectomy is to no advantage (exception: urinary stasis). Cyproterone acetate does neither yield better nor worse results regarding survival than estrogen alone, but has fewer side effects. Estrogens and cyproterone acetate produce a rise of serum prolactin justifying the use of bromocriptine (or lisuride). Estramustine phosphate should be reserved for relapsing prostatic cancer.
 ...
PMID:[Current aspects of hormonal therapy in prostate cancer]. 728 76

Transrectal ultrasonotomography was performed in 44 patients with prostatic cancer before, during, and after estramustine phosphate (Estracyt) administration. In 75.7% of 37 previously untreated patients, the deformity of the horizontal section of the prostate with prostatic cancer was corrected considerably, while in 89.2%, prostatic weight was remarkably reduced. In 57.1% of seven previously treated patients, appreciable changes were also observed in the shape and weight of the prostate. We concluded that estramustine phosphate was effective not only for untreated prostatic cancer, but also, at least in some degree, for relapsed cases.
 ...
PMID:The effect of estramustine phosphate on prostatic cancer estimated by transrectal ultrasonotomography. 730 54

The effect of chemotherapy for treatment of prostatic cancer was studied in two different types of human prostatic tumors grown in nude mice based on growth curves and histological examination. As single agents, cis-platinum and vincristine showed significant growth inhibition in both strains; cyclophosphamide, methotrexate, Adriamycin, and peplomycin were effective in only one strain, whereas 5-fluorouracil (5-FU), ACNU, and Estracyt were not effective in either strain, even at relatively high doses. A study was also carried out on multimodal combination chemotherapy with fewer side effects, and such therapy is in clinical use. The treatment is composed of VPM (vincristine, peplomycin, and methotrexate) followed by CCF (cis-platinum, cytosine arabinoside, and 5-FU) and ACF (Adriamycin, cytosine arabinoside, and 5-FU). Antitumor effects related to synchronization of tumor cells were investigated by sequential autoradiography and DNA histography.
 ...
PMID:Evaluation of chemotherapy of prostatic cancer in nude mice. 734 73

Estramustine phosphate, a nitrogen mustard derivative of estradiol used for the treatment of advanced prostatic cancer, was administered orally to man, rat and dog and the plasma concentrations of its unconjugated metabolites were determined by high performance liquid chromatography. In all species the drug was rapidly and completely dephosphorylated prior to reaching the peripheral circulation. In man and the rat, the 17-keto analogue of estramustine (estromustine) was the mamor metabolite found in plasma with considerably lesser amounts of estramustine itself. In the dog, significant concentrations of both estramustine and estromustine were present. Highly elevated levels of both estrone and estradiol, as a result of cleavage of the nitrogen mustard from the steroid, were observed in all species. Chronic administration of therapeutic doses of estramustine phosphate to man did not result in any apparent accumulation of circulating metabolites. The study suggests that the metabolite, estromustine, in addition to estramustine, may play an important role in the therapeutic efficacy of estramustine phosphate.
 ...
PMID:Estramustine phosphate: plasma concentrations of its metabolites following oral administration to man, rat and dog. 736 Sep 97


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