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)

In 17 prostatic cancer patients, changes in the plasma lipoprotein pattern, including high density lipoprotein (HDL) subfractions, and in glucose tolerance were compared after 6 months on parenteral polyestradiol phosphate (PEP; Estradurin, 80 or 160 mg/month) with the respective changes in orchiectomized patients. In the estrogen group there was no change in the total serum cholesterol level, whereas in the orchiectomy group an increase of 10% was observed. Estrogen therapy resulted in a significant increase of serum HDL (11%) and HDL2 cholesterol (26%) levels; in the orchiectomy group these fractions remained unchanged. Estrogen therapy induced a significant decrease in total serum triglycerides (24%) and in low density lipoprotein triglycerides (27%); in the orchiectomy group reverse changes were observed. PEP treatment caused changes in the serum lipoprotein pattern, which apparently decreases the risk of atherosclerosis.
 ...
PMID:Effects of orchiectomy and polyestradiol phosphate therapy on serum lipoprotein lipids and glucose tolerance in prostatic cancer patients. 235 Nov 92

Prostatic tissue removed at the time of cystoprostatectomy was separated into periurethral and peripheral zones. Homogenized tissue was incubated with [1,2,6,7(3)H] androstenedione in the presence or absence of an aromatase inhibitor, 4-hydroxyandrostenedione (4-OHAD) and a 5 alpha-reductase inhibitor 4-MA (N,N-diethyl-4-methyl-3-oxo-4-aza-5 alpha-androstane 17 beta-carboxamide). Estrogen formation was determined by reverse isotope dilution of [3H] estrone and [3H] estradiol and crystallization to constant specific activity. Control incubations were carried out in parallel utilizing heated prostatic tissue. Total estrogens produced in the periurethral zone in patients with benign prostatic hyperplasia (BPH) was 223 fmol/mg protein/hr (SE +/- 57) compared to 102 fmol (SE +/- 17) in patients without BPH. Estrogen formation in the peripheral zone was 175 fmol (SE +/- 69) and 105 fmol (SE +/- 26) in patients with and without BPH, respectively. The prostatic aromatase exhibits Michaelis-Menton kinetics with an apparent Km of 90 nM. 4-OHAD inhibited aromatization in the prostatic tissue by 57-93%. Aromatization was also strongly inhibited by 4-MA, indicating that 4-MA is a potent aromatase as well as a 5 alpha-reductase inhibitor in this tissue. These results suggest that aromatization of androgens to estrogens in the human prostate proceeds at a substantial rate and that local estrogen formation could preexist and be a factor in the etiology of BPH and prostatic cancer.
 ...
PMID:Estrogen formation in human prostatic tissue from patients with and without benign prostatic hyperplasia. 243 1

Between 1977 and 1986, 11 patients with painful gynecomastia after DES therapy were referred for palliative radiotherapy. The treatment regimens varied from 20 Gy in 5 fractions to 40 Gy in 20 fractions. All 11 patients had satisfactory pain relief on follow-up. All 7 patients who had more than 6 months follow-up had complete relief of mammalgia. The average interval between completion of radiotherapy to complete relief of mammalgia was 3.6 months. This study revealed that radiotherapy is highly effective in palliating mammalgia associated with gynecomastia after DES therapy in prostate cancer patients.
 ...
PMID:Effective radiotherapy in palliating mammalgia associated with gynecomastia after DES therapy. 245 32

The parenchymal damage of the liver after estrogen therapy for prostatic cancer, mainly treated with diethylstilbestrol diphosphate (DES-DP), was studied in the six autopsied cases, herein. The parenchymal disorder of the liver was "nonalcoholic steatohepatitis", reported by Ludwig et al., and its degree of disorder was dependent upon the administered dose of estrogen. The acceptable total dose of DES-DP was supposed to be about 150 g at maximum, according to the various degrees of damage examined histopathologically in the six cases who were administered at total doses of DES-DP from 12.6 g to 619 g. Comparison of the histopathologic damage to the liver function tests performed within 10 days before death revealed that only the serum levels of cholinesterase (ChE) were abnormally decreased, suggesting its importance to predict the degree of "nonalcoholic steatohepatitis" by monitoring of ChE.
 ...
PMID:[Liver disorder owing to estrogen therapy in prostatic cancer, examined histopathologically in six autopsy cases]. 262 17

We have examined the value of cholinesterase (ChE) that indicates the preservation ability of liver function, to assess the liver disorder owing to diethylstilbestrol diphosphate (DES-DP) administration in 25 prostatic cancer patients without castration. The correlation between ChE and the other factors such as age, total dose of DES-DP, duration of administration or ratio (total dose/duration), were studied by means of multiple regression analysis (MRA). In sixteen patients treated for less than 6 months, ChE was correlated with all factors by MRA with the coefficient of 0.645, and the coefficients of simple correlation between ChE and total dose and between ChE and administered duration, were -0.521 (p less than 0.05) and -0.596 (p less than 0.05), respectively. In nine patients treated for more than 6 months, ChE was correlated with all factors by MRA with the coefficient of 0.803, and the coefficient of simple correlation between ChE and ratio was -0.707 (p less than 0.05). According to these results and the permissible range of ChE, the total dose of administration for less than 6 months was estimated to be under 50 gram and its duration was within 100 days. The ratio in patients administered for more than 6 months was under 300 mg/day. Therefore, as far as the long-term hormonal treatment for prostatic cancer and preservation of liver function, we concluded that total dose of DES-DP should be less than 50 gram in less than 100 days for induction therapy and the daily dose of DES-DP should be less than 300 mg/day for maintenance therapy.
 ...
PMID:[Liver disorder owing to estrogen therapy in prostatic cancer. The correlation between serum level of cholinesterase and dose of diethylstilbestrol diphosphate]. 262 18

To assess if and by which mechanisms pharmacological estrogen treatment induces gallstone disease, we examined patients with recently diagnosed prostatic cancer randomly allocated to estrogen therapy (n = 37) or orchidectomy (n = 35). According to gallbladder ultrasonography, after 1 yr new gallstones had developed in 5 of 28 estrogen-treated patients, compared with 0 of 26 orchidectomized patients (P = 0.03). Estrogen therapy for 3 mo increased the relative concentration of cholesterol and cholesterol saturation of bile by approximately 30% (n = 10). Serum LDL cholesterol was reduced by approximately 40%, and its relative change related inversely to that of bile cholesterol (Rs = -0.77). There were no changes in biliary or serum lipids after orchidectomy (n = 9). Secretion rates of biliary lipids were measured with a duodenal perfusion technique. Patients on chronic estrogen therapy (n = 5) had approximately 40% higher biliary excretion rates of cholesterol than age-matched controls (n = 7). Phospholipid secretion was also higher, but no difference in bile acid secretion was found. We conclude that an increased hepatic secretion of cholesterol results in increased cholesterol saturation of bile and an enhanced rate of gallstone formation during estrogen treatment. The changes in bile cholesterol seem to be related to the induced changes in serum lipoprotein metabolism.
 ...
PMID:Estrogen-induced gallstone formation in males. Relation to changes in serum and biliary lipids during hormonal treatment of prostatic carcinoma. 276 Feb 14

Patients (154) with clinical stage D2 prostate cancer with no previous endocrine therapy or chemotherapy received the combination therapy with the pure antiandrogen Flutamide and the LHRH agonist [D-Trp6]LHRH ethylamide for an average of 22 months (3-49 months). The objective response to the treatment was assessed according to the criteria of the US NPCP. There was a 6.3-fold increase (29.2 vs 4.6%) in the percentage of patients who achieved a complete response as compared to the results achieved in five recent studies limited to removal (orchiectomy) or blockade (DES or Leuprolide) of testicular androgens. Only 4.5% of patients did not respond to the combination therapy as compared to an average of 18% by standard therapy. The duration of response is also significantly increased in the patients who received the combination therapy. The death rate was decreased by approximately 2-fold between 2 and 3 yr of treatment. The marked (6.3-fold) improvement in the rate of complete objective responses coupled with the 4-fold decrease in the number of non-responders, the increased duration of the positive responses and the 2-fold decrease in the death rate at 2-3 yr of treatment are obtained with the combination therapy using Flutamide and castration with no or minimal secondary effects.
 ...
PMID:Combination therapy with flutamide and castration (orchiectomy or LHRH agonist): the minimal endocrine therapy in both untreated and previously treated patients. 296 37

Analogs of GnRH constitute a new category of drugs available for the treatment of advanced prostatic cancer. The efficacy and safety of GnRH analogs in the treatment of this disease is now well established. These compounds represent an important alternative therapy for advanced prostatic cancer patients who do not wish to undergo orchiectomy or for whom DES is not tolerable because of the risk of cardiovascular complications. The advent of the monthly depot form of these drugs will make treatment more convenient and less invasive and will enhance patient compliance.
 ...
PMID:Gonadotropin-releasing hormone analogs and prostatic cancer. 296 39

Superactive analogues of luteinizing hormone-releasing hormone (LHRH) have now widely been used in the management of metastatic prostate cancer. In a multicentric study, we have studied the effectiveness of buserelin in patients with previously untreated histologically confirmed metastatic prostate cancer. Fifty-eight patients were enrolled in the study and are now followed for at least 12 months. The treatment consisted of 500 micrograms buserelin administered subcutaneously (s.c.) 3 times daily for the first seven days and thereafter a thrice-daily dose of 400 micrograms buserelin administered intranasally (i.n.). A continuous reduction of testosterone to castrate levels could be obtained in all patients. The following objective responses were seen during the 12 months study period: 5 patients (8.6%) achieved complete regression after 3-10 months (mean 6.4 m); 24 patients (41.4%) achieved partial regression after 1-12 months (mean 4.5 m); 7 patients (12%) remained stable throughout the study; 22 patients (32.3%) developed progression after 2-12 months (mean 7.2 m). Toxicity was minimal. Only one patient dropped out of the study because of side effects. These results are comparable with results of other forms of hormonal treatment of prostate cancer. Long-term results of 3 EORTC GU group comparative studies in metastatic prostate cancer are now available. The first study, 30761, compared cyproterone acetate, medroxy-progesterone acetate, and DES. No differences between the 3 treatment arms were observed except for medroxy-progesterone acetate, which showed less therapeutic effect in the dosage used. Protocol 30762 compared DES and estramustine phosphate. No significant difference in objective response and survival was noted. Protocol 30805 studied a comparison between orchiectomy alone and orchiectomy supplemented by cyproterone acetate and DES. Again no statistically significant difference was found between the three therapeutic arms.
 ...
PMID:Results of a Dutch trial with the LHRH agonist buserelin in patients with metastatic prostatic cancer and results of EORTC studies in prostatic cancer. 296 60

To improve the inhibition of prostate cancer growth obtained by surgical or chemical castration (estrogens or LHRH analogs), blockade of the action of residual androgens of adrenal origin has been proposed. Among antiandrogens acting through the androgen receptor (AR), the nonsteroid anandron (RU 23908) has several advantages over available compounds: megestrol acetate and cyproterone acetate, both steroids, bind substantially to other hormone receptors (progestin, gluco- and mineralocorticoid); and anandron binds only to AR. The nonsteroid flutamide is a prodrug converted to the active metabolite, hydroxyflutamide; anandron is well absorbed on oral administration of an active dose and intact compound disappears slowly from plasma. This may explain why, although in vitro anandron interacts very transiently with AR, in vivo a high level of untransformed anandron is present at the receptor site to induce its antiandrogenic activity. Animal experiments confirm that anandron can counteract the effect of adrenal androgens and inhibit the LHRH analog-induced initial increase in androgen ("flare-up"). Thus, in rats castrated either surgically or by buserelin or DES and supplemented with adrenal androgens (since endogenous adrenal secretion is very low in this species compared to man), anandron decreased prostate weight to control levels. The administration of buserelin to intact rats over 15 days resulted in a significant increase in prostate weight between Days 1 and 5. The addition of anandron to the buserelin inhibited this increase and, furthermore, led to a far greater decrease in prostate weight than that due to buserelin alone at 15 days, indicating a synergy of action.
 ...
PMID:Pharmacology of an antiandrogen, anandron, used as an adjuvant therapy in the treatment of prostate cancer. 300 70


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>