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)

Estramustine, a conjugate of estradiol-17 beta and nor-nitrogen mustard currently used in prostatic cancer, was found to exert a dose-dependent antiproliferative effect on the human malignant glioma cell lines U-251 MG and U-105 MG. At equimolar concentrations the inhibitory effects of the estramustine complex were clearly more pronounced than those of estradiol and nor-nitrogen mustard given alone or in combination. Flow cytometric analyses support the concept that estramustine cytotoxicity is mediated via separate mechanisms. The intact estramustine complex may be important for effects related to microtubule function which add to the cytotoxic potential of the alkylating component.
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PMID:Effects of estramustine and its constituents on human malignant glioma cells. 236 85

Endocrine therapy for urological tumor includes estrogen therapy for prostatic carcinoma. This endocrine therapy is one of the most firmly established therapeutic methods in the field of clinical oncology. However, confusion exists about how long this treatment remains effective and whether it prolongs survival, since estrogen can create cardiovascular complications in patients with prostatic carcinoma. Recently, new endocrine agents have been developed to compensate for the problems of estrogen therapy and to make treatment more effective. Estramustine sodium phosphate is medicine for internal use prepared by combining estradiol with nitrogen mustard. This hormonal chemotherapeutic agent has proved effective in 98% of treated patients. Most of the side effects of this agent have been observed in the digestive organs. Chlormadinone acetate, a progestational agent, has proved more effective against early prostatic carcinoma than against late-stage disease. LHRH analogue, which is now drawing much attention as a "chemical castration" agent for prostatic cancer patients, exerts an effectiveness equal to medium-dose estrogen treatment. The above three agents for the treatment of prostatic carcinoma should become increasingly popular in the future.
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PMID:[Hormone therapy of male genital cancer (prostatic cancer)]. 244 64

The nitrogen mustard derivatives of 4-phenylbutyric acid and L-phenylalanine, called chlorambucil (Chl) and melphalan (Mel), respectively, have been incorporated into several peptide hormones, including luteinizing hormone-releasing hormone (LH-RH). The alkylating analogues of LH-RH were prepared by linking Chl, as an N-acyl moiety, to the complete amino acid sequence of agonistic and antagonistic analogues. These compounds, in particular the antagonistic analogues, showed much lower potency than their congeners carrying other acyl groups. To obtain highly potent alkylating analogues of LH-RH, the D enantiomer of Mel was incorporated into position 6 of the native hormone and some of its antagonistic analogues. Of the peptides prepared, [D-Mel6]LH-RH (SB-05) and [Ac-D-Nal(2)1,D-Phe(pCl)2,D-Pal(3)3,Arg5,D-Mel6,D-Ala10++ +]LH-RH [SB-86, where Nal(2) is 3-(2-naphthyl)alanine and Pal(3) is 3-(3-pyridyl)alanine] possessed the expected high agonistic and antagonistic activities, respectively, and also showed high affinities for the membrane receptors of rat pituitary cells, human breast cancer cells, human prostate cancer cells, and rat Dunning R-3327 prostate tumor cells. These two analogues exerted cytotoxic effects on human and rat mammary cancer cells in vitro. Thus these two D-Mel6 analogues seem to be particularly suitable for the study of how alkylating analogues of LH-RH could interfere with intracellular events in certain cancer cells.
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PMID:Highly potent analogues of luteinizing hormone-releasing hormone containing D-phenylalanine nitrogen mustard in position 6. 254 7

Estramustine (EM) is a conjugate of estradiol and nor-nitrogen mustard (nor-HN2), which is effective in the treatment of prostate cancer. We have compared the effect of EM with that of the known microtubule inhibitor vinblastine (VLB) on the following functions of malignant MO4 mouse cells and of DU-145 human prostate cancer cells in vitro: directional migration, invasion; and the organization and the assembly/disassembly equilibrium of microtubule complexes. The circular area covered by cells migrating from an aggregate explanted on a solid substrate was taken as an index of directional migration. Invasion was studied through confrontation of MO4 or DU-145 cells with fragments of embryonic chick heart in organ culture. Microtubules were investigated immunocytochemically and through immunodetection on protein blots. VLB and EM inhibited directional migration and invasion of MO4 and DU-145 cells in a dose-dependent manner; equimolar combinations of estradiol plus nor-nitrogen mustard did not mimic these effects. At anti-invasive concentrations VLB led to partial disassembly of microtubule complexes, whereas EM resulted in an abnormal pattern of microtubule complexes without alteration of the overall assembly/disassembly equilibrium. Combined treatment with VLB and EM resulted in an enhanced VLB effect, namely complete disassembly. In all tests DU-145 cells were more sensitive to both VLB and EM than were MO4 cells, and the effects were less reversible. The present experiments showed that EM shares an anti-invasive activity with other microtubule inhibitors.
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PMID:Antiinvasive activity of estramustine on malignant MO4 mouse cells and on DU-145 human prostate carcinoma cells in vitro. 334 62

Although various complications such as electrolyte imbalance and urinary infection are known to be induced by ureterosigmoidostomy, it is still a surgical technique difficult to ignore since it allows patients to lead an almost normal life without the encumbrance of external urinary devices. At our hospital, we performed eighteen ureterosigmoidostomy operations between 1976 and 1985. Herein, we review the postoperative conditions of electrolyte, renal function and other complications. The patients (16 male, 2 female) were between 53 and 72 years old, the mean age being 61.5 years. The primary diseases were bladder tumor (14 patients), prostatic cancer (2), carcinoma of the female urethral diverticulum (1) and urethral stricture (1). As to the electrolytes, both serum Na and serum K values fluctuated within the normal range. Hyperchloremia was detected in 4 cases (22.2%), but it was only slightly above the normal range and the conditions were more or less stabilized a year after the operation. Although blood urea nitrogen had a tendency to elevate one or two years after the operation, serum creatinine fluctuated within the normal range. During the observation period, only 7 of the 18 cases (38.9%) showed complications, the major complication being pyelonephritis (3 cases). Postoperative excretory urogram revealed slight to medium hydronephrosis two months after the operation in 9 of the 18 cases (50%), but most of these conditions were normalized within a year. Four patients died after leaving hospital; 3 due to the recurrence of cancer and one due to pneumonia. The 14 other outpatients are enjoying a normal life without the use of any external urinary device.
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PMID:[Ureterosigmoidostomy--clinical review of 18 cases]. 344 31

Estramustine, a nitrogen mustard derivative of estradiol-17 beta widely used for treatment of prostatic cancer, was found to inhibit the proliferative response of mouse lymphocytes to T (concanavalin A) and B (lipopolysaccharide) cell mitogens in vitro. Concanavalin A-induced lymphoproliferation was considerably more sensitive to the antiproliferative effect of estramustine than lipopolysaccharide-stimulated proliferation. The concentration of estramustine selectively inhibiting T lymphocyte proliferation was only active when present during the first 24 h of culture and could be overcome by exogenously added interleukin 2. Estramustine was shown to directly inhibit the production of interleukin 2 in concanavalin A-stimulated lymphocyte cultures without affecting the expression of interleukin 2 receptors. Thus the preferential inhibitory effect of estramustine on mitogen-induced T lymphocyte activation is apparently mediated by interference with the production or release of interleukin 2.
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PMID:Inhibition of T lymphocyte activation by estramustine: dose-dependent interference with IL-2 production and later proliferation events. 387 48

In this clinical trial of men with advanced prostatic cancer no longer responsive to hormone therapy 189 were randomized to receive estramustine phosphate, methotrexate or cis-platinum. Response evaluations were done in 158 cases. Objective response rates (complete, partial or stabilization of disease) were 34 per cent for estramustine phosphate, 36 per cent for cis-platinum and 41 per cent for methotrexate. Subjective parameters indicated a substantial advantage for pain improvement with methotrexate or cis-platinum over estramustine phosphate. Probabilities of continued response indicated some advantage for methotrexate and median response durations at this time were twice as long for methotrexate (32 weeks) as for cis-platinum (16 weeks), with estramustine phosphate intermediate (23 weeks). Survival rates for the original treatment randomization groups were not different at this time. Side effects of estramustine phosphate consisted primarily of nausea and vomiting and/or anorexia but to a lesser extent than with cis-platinum. These effects were somewhat less for methotrexate, for which the major side effects were stomatitis and leukopenia, as well as hepatic toxicity reflected by elevated serum glutamic oxaloacetic transaminase levels. Other side effects of cis-platinum were less than for methotrexate (no stomatitis), except for signs of renal toxicity (elevations in blood urea nitrogen and serum creatinine), which were greater. Methotrexate had a relatively high level of activity against metastatic, progressive, hormone nonresponsive prostatic cancer, with side effects that were substantial but manageable.
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PMID:Comparison of estramustine phosphate, methotrexate and cis-platinum in patients with advanced, hormone refractory prostate cancer. 634 29

Estramustine phosphate is approved by the Food and Drug Administration for oral use in the palliative treatment of patients with metastatic and/or progressive carcinoma of the prostate. Estramustine is a conjugate of 17 beta-estradiol and the carbamate of nitrogen mustard. Although its therapeutic efficacy has been demonstrated, it is not clear to what extent each constituent contributes to estramustine's effectiveness. Estramustine phosphate therapy achieves objective response rates of 60-90 percent in advanced stage D prostatic cancer patients with no prior hormonal therapy. These results are consistent with those obtained with conventional hormonal therapy in similar patient populations. Therapeutic efficacy does not appear to increase when estramustine is used concurrently with other cytotoxic chemotherapeutic agents. An objective response rate of 20-30 percent can be anticipated in patients refractory to conventional hormonal therapy. It is in this group, the estrogen-resistant patients, that estramustine shows the most promise. Adverse effects of estramustine are similar to those of diethylstilbestrol. Gastrointestinal and cardiovascular side effects appear to be the most important and may be severe enough to require discontinuation of therapy.
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PMID:Estramustine phosphate sodium. 637 12

Estracyt is a new drug for treatment of prostatic cancer, which is a molecule combining estradiol and nornitrogen mustard by a carbamate link. Estracyt is completely dephosphorylated prior to reaching the peripheral circulation after oral administration of the drug to men. Estramustine, i. e. dephosphorylated Estracyt, appears to be metabolized in liver as follows: Estramustine leads to estromustine leads to nitrogen mustard + estrone. There is a large amount of estramustine binding protein (EMBP) in the cytosol 3.5 S fraction of human prostatic cancer tissue, which is involved with the selective uptake and long term retention of both estramustine and estromustine in prostate. The anticancer action of Estracyt appears to be the sum of the direct prostatic action of estramustine and estromustine and the indirect prostatic action of free estradiol-17 beta and estrone via the inhibition of hypothalamo-pituitary axis. Estracyt Research Group in Japan concluded that Estracyt was effective in 38% of reactivated prostatic cancer patients (15% (I-C, I-B), 23% (I-A, O-B, O-C]. Side effects of this drug at the time of 3 months treatment is as follows: gastrointestinal disturbance in 36%, edema in 15%, and hepatic disorder in 7%.
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PMID:[Pharmacology and metabolism of a new therapeutic drug for prostatic cancer "Estracyt"]. 642 61

Estracyt (estramustine phosphate) is a nitrogen mustard derivative of estradiol-17 beta which is rapidly dephosphorylated to yield estramustine. Estramustine is metabolized to estromustine mainly in the liver. Both estramustine and estromustine are retained in rat prostate with a high degree of specificity. This retention is due to the binding of estramustine and/or estromustine to a protein called EMBP (estramustine binding protein). When estimated by HPLC, the molecular weights of these estramustine binding components in rat prostate are 45,000-50,000 and 25,000-30,000, respectively. HPLC and glycerol density gradient analysis clearly demonstrated the occurrence of EMBP in a cytosol preparation from human prostatic cancer tissue. When estimated by HPLC, the molecular weights of estramustine binding components are 45,000 and 25,000 daltons, respectively. In addition, results of effectiveness of Estracyt studied under a cooperative research group in Japan, are reported in this paper. Effectiveness was evaluated at 3 months of the treatment on 121 patients with untreated prostatic cancer (Study I) and 95 patients with reactivated cancer (Study II), at 12 months of the treatment on 68 patients in Study I and 85 patients in Study II, and at 24 months on 37 patients in Study I and 23 patients in Study II. At 3 months of the treatment, Estracyt was effective in 89% of untreated prostatic cancers, and 38% of reactivated prostatic cancers. At 24 months of the treatment, this drug was effective in 65% of untreated prostatic cancers and 30% of reactivated ones. Estracyt is especially recommended as a first-choice drug for both the untreated patients with poorly differentiated adenocarcinoma and reactivated cancer.
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PMID:[Estracyt (estradiol-nitrogen mustard complex)--estramustine binding protein and its specificity]. 648 30


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