UMLS:C0376358 - FACTA Search

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)

Six patients with advanced prostatic cancer who had been treated by long-term administration of LH-RH agonistic preparations (Buserelin or Leupron) were tested for their pituitary-testicular endocrine functions. Serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), prolactin (PRL), estradiol (E2) and dihydrotestosterone (DHT) were measured consecutively. In all medically castrated patients, serum levels of LH, FSH, T, DHT and E2 were suppressed and particularly serum T levels were below the castration level of 1.0 ng/ml. On the other hand, serum PRL levels were unchanged after the long-term treatment with the agonists. Serum LH and FSH levels failed to respond to LH-RH stimulation after the treatment, whereas serum T responded to stimulation by human chorionic gonadotropin (hCG) to various degrees. It was remarkable that, in 4 out of 6 medically castrated patients treated up to more than 3 years, serum T response levels above 1.0 ng/ml were noted. It is suggested that testicular endocrine function to secrete T and DHT in patients under treatment with long-term LH-RH agonist administration are still preserved in response to hCG stimulation.
...
PMID:[Testicular endocrine function in patients with prostatic cancer receiving medical castration by long-term administration of LH-RH agonists]. 251 45

The combination of a long-acting delivery system for the agonist [D-Trp6]luteinizing hormone-releasing hormone ([D-Trp6]LH-RH) with modern somatostatin analogs was studied in the Dunning R-3327H rat prostate cancer model. Microcapsules of [D-Trp6]LH-RH releasing 25 micrograms/day were injected once a month. In the first experiment the adjunct was the somatostatin analog D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 (RC-121), administered at a dose of 2.5 micrograms twice a day, and the therapy was continued for 70 days. Tumor volume was significantly decreased by [D-Trp6]LH-RH microcapsules or RC-121 given alone. The combination of microcapsules and analog RC-121 caused a greater inhibition of tumor growth than the single agents. Similar effects were seen when the percent increase in the tumor volume was examined. The inhibition of tumor growth caused by the [D-Trp6]LH-RH microcapsules was greater than that caused by RC-121. The combination of the two agents was again the most effective, resulting in the smallest increase in tumor volume. Tumor weights were much lower in the groups treated with microcapsules or RC-121 alone than in controls. The lowest tumor weights were obtained in the group that received the combination of [D-Trp6]LH-RH microcapsules and RC-121. Similar results were obtained in the second experiment, in which the animals were treated for a period of 83 days with microcapsules containing the somatostatin analog D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160) that released 5 micrograms/day and were injected twice a month alone or in combination with microcapsules of [D-Trp6]LH-RH. Microcapsules of analog RC-160 given alone significantly decreased tumor growth as measured by the final tumor volume, the percentage change from the initial tumor volume, and the reduction in tumor weight. The inhibition of tumor growth induced by [D-Trp6]LH-RH microcapsules was greater than that caused by RC-160. The most striking decrease in tumor weight and volume was obtained in animals treated with microcapsules of [D-Trp6]LH-RH combined with the delayed delivery system for RC-160. The overall response to the combination therapy could reflect the inhibition by somatostatin analogs of the proliferation of prostate cancer cells through a decrease in growth hormone and prolactin release and interference with endogenous growth factors, in addition to the main effect, which is the suppression by [D-Trp6]LH-RH of the growth of androgen-dependent tumor cells. Our results indicate that somatostatin analogs enhance the inhibitory effects of [D-Trp6]LH-RH on the growth of prostate tumors. The administration of somatostatin analogs in combination with microcapsules of [D-Trp6]LH-RH might improve clinical response in patients with advanced prostate carcinoma.
...
PMID:Somatostatin analogs as adjuncts to agonists of luteinizing hormone-releasing hormone in the treatment of experimental prostate cancer. 289 Jan 64

In this pilot study the treatment of advanced prostatic cancer with cyproteronacetate (AndrocurR) is compared with the treatment of a lower dose cyproteronacetate plus lisuride (DoperginR), an anti-prolactin derivative. Treatment was continued until progression and/or the appearance of serious side effects necessitated termination. The duration of the treatment with cyproteronacetate plus lisuride ranged from 2 to 38 months. Most cases showed a partial response, evaluated on the basis of lower levels of prostatic acid phosphatase, relief of bone pain and reduction of bone metastases. Serious side-effects other than impotence did not occur.
...
PMID:Treatment of advanced prostatic cancer with anti-androgens alone and a combination of anti-androgen with anti-prolactin--a pilot study. 294 68

The combination of hormonal treatment based on a long-acting delivery system for the agonist [6-D-tryptophan]luteinizing hormone-releasing hormone ([D-Trp6]-LH-RH) with the chemotherapeutic agent Novantrone (mitoxantrone dihydrochloride) was studied in the Dunning R3327H rat prostate cancer model. Microcapsules of [D-Trp6]-LH-RH formulated from poly(DL-lactide-co-glycolide) and calculated to release a controlled dose of 25 micrograms/day were injected intramuscularly once a month. Novantrone (0.25 mg/kg) was injected intravenously once every 3 weeks. Three separate experiments were carried out. When the therapy was started 45 days after transplantation and continued for 70 days, tumor volume in the presence of the microcapsules (966 +/- 219 mm3) or Novantrone (3606 +/- 785 mm3) given alone was significantly decreased compared to controls (14,476 +/- 3045 mm3). However, the combination of microcapsules and Novantrone caused a greater inhibition of tumor growth (189 +/- 31 mm3) than the single agents. Similar effects were seen when the percent increase in tumor volume was examined. Tumor volume increased 10,527 +/- 1803% for the control group. The inhibition of growth caused by the [D-Trp6]LH-RH microcapsules alone (672 +/- 153% increase in volume) was again greater than that caused by Novantrone alone (2722 +/- 421% increase). The combination of the two agents was again the most effective, resulting in an increase in tumor volume of only 105 +/- 29%. Control tumors weighed 30.0 +/- 6.5 g. Tumor weights were much less in the groups treated with either microcapsules (3.28 +/- 0.69 g) or Novantrone (19.53 +/- 3.3 g) alone. The lowest tumor weights after 70 days of treatment were obtained in the group that received the combination of [D-Trp6]LH-RH microcapsules and Novantrone (1.02 +/- 0.2 g). Testes and ventral prostate weights were significantly diminished by the administration of microcapsules of [D-Trp6]LH-RH alone or in combination with Novantrone. In both of these groups, luteinizing hormone and prolactin levels were reduced and serum testosterone was suppressed to undetectable levels. Similar results were obtained in two other experiments in which the duration of treatment was 60 or 105 days. These results suggest that the overall response could reflect the inhibition of proliferation of hormone-independent cancer cells by Novantrone in addition to the suppressive effect of [D-Trp6]LH-RH on the growth of androgen-dependent tumor cells. The administration of Novantrone in combination with microcapsules of [D-Trp6]LH-RH might produce a better clinical response than LH-RH analog alone in patients with advanced prostate carcinoma.
...
PMID:Combination of a long-acting delivery system for luteinizing hormone-releasing hormone agonist with Novantrone chemotherapy: increased efficacy in the rat prostate cancer model. 294 45

Thirteen patients with untreated prostate cancer were treated initially with subcutaneous 0.5 mg D-Trp6-LH-RH daily for the first week, 0.1 mg daily for the next three weeks and thereafter with intramuscular depot preparations of 3.2 mg every three weeks. Serum testosterone was suppressed to castration levels. Serum LH, FSH and prolactin were reduced, serum cortisol did not change. 10/13 patients showed remissions, as shown by transrectal prostate volumetry, cytological regression grading, serum phosphatases and clinical status. 3/13 tumors showing progression were undifferentiated and androgen-resistant. The investigated compound seems to be effective in selecting androgen sensitive tumors and may be a possible alternative to orchiectomy.
...
PMID:[Decapeptyl (D-Trp6-LH-RH) in the therapy of prostatic cancer with reference to the intramuscular administration of a depot preparation]. 294 71

Survival of patients who received endocrine therapy as first-line treatment for their prostatic cancer was statistically analysed in relation to several parameters, primary tumour stage, metastatic status, age, pretreatment plasma hormone concentrations and Gleason grade. Prognostic indices were derived for both M0 and M1 patients in which Gleason grade and plasma testosterone concentrations were significant prognostic factors. In the M1 patients growth hormone values were also significant and to a lesser degree age. The relationship of Gleason grade to testosterone, growth hormone, prolactin, the gonadotrophins and age was also analysed. No significant differences in any of these hormones was noted with increasing Gleason grade but the age of patients with Grade 5 tumours was significantly lower.
...
PMID:Steroid hormone concentrations in relation to patient prognosis and prostate tumour grade. 312 25

Eight patients with advanced prostatic carcinoma (ages 59 to 78 years) were treated with a potent gonadotropin-releasing hormone (GnRH) agonist analog (buserelin, Hoechst; 600 micrograms intranasally, 3 times daily) and orchiectomized after 6 months of treatment. Endocrine responses were followed by serum hormone measurements during agonist treatment and for 3 months after orchiectomy. Six other patients (65 to 86 years) with advanced prostatic cancer had been orchiectomized as the first therapeutic measure and their blood samples were used as controls. In the GnRH agonist-treated patients, serum immunoreactive luteinizing hormone (LH) and follicle stimulating hormone (FSH) decreased after initial stimulation by 70 to 80%, within 1 to 3 weeks (P less than 0.01). FSH partly recovered (P less than 0.05) after the first month of treatment. Serum prolactin (PRL) displayed a slight tendency to decline during buserelin treatment (P less than 0.05). Serum total and free testosterone (T) of the buserelin-treated patients decreased to the castrate range within 3 to 4 weeks after an initial 5-day increase (P less than 0.01). Serum progesterone and 17-hydroxyprogesterone (17-OHP-4) decreased to the castrate range (by 50 to 70%) in 1 week. Only minor changes were observed in sex hormone binding globulin (SHBG). Significant, acute elevations of LH, FSH, T, and 17-OHP-4 were observed only on day 1 after an injection of buserelin (500 microgram i.m.) and not when assessed between day 7 and month 6 of treatment. After 6 months of buserelin treatment, orchiectomy did not affect the serum steroids measured. After orchiectomy, immediate increases in serum LH, and somewhat later in FSH, were seen in the control patients.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Pituitary-testicular function of prostatic cancer patients during treatment with a gonadotropin-releasing hormone agonist analog. I. Circulating hormone levels. 312 45

In order to clarify the effects of androgen blockade on the hypothalamic-pituitary-testicular axis in man, four patients with advanced prostate cancer, not previously treated, were given oral flutamide, 250 mg three times daily for 9 days. Before, and 7, 8 and 9 days after starting flutamide treatment, on separate days, the following tests were performed: a gonadotrophin pulsatility study, with 20 min interval blood sampling for 12 h, a naloxone test and a GnRH test. Flutamide induced a significant increase in both LH and FSH pulse frequency, while pulse amplitudes and plasma integrated concentrations (IC) of LH and FSH were unaffected. Plasma integrated concentrations of testosterone and oestradiol rose significantly, while that of prolactin was unaffected. The increase in plasma LH concentration induced by naloxone injection was abolished by flutamide treatment. On the other hand, the small FSH response to naloxone was unaffected by flutamide treatment. Response to GnRH was unaffected by flutamide. These results suggest that flutamide exerts effective androgen blockade at the hypothalamic level, since, despite increased plasma testosterone concentrations, gonadotrophin pulse frequency increased and the LH response to naloxone was abolished.
...
PMID:The effect of androgen blockade on pulsatile gonadotrophin release and LH response to naloxone. 312 93

The therapy for the treatment of prostate cancer and other sex-steroid-dependent tumors based on agonists of LH-RH has been made more practical and efficacious by the development of a long-acting formulation of microcapsules of D-Trp-6-LH-RH for controlled release. Antiandrogens, which neutralize the effect of endogenous androgens, have been used also in the management of prostate cancer in man. The effects of a simultaneous administration of the antiandrogen flutamide and microcapsules of the agonist D-Trp-6-LH-RH were studied in the Dunning R-3327H rat prostate adenocarcinoma model to determine whether the combination of these two drugs might inhibit tumor growth more effectively than single agents. Microcapsules of D-Trp-6-LH-RH, calculated to release a controlled dose of 25 micrograms/day for a period of 30 days were injected intramuscularly once a month. Flutamide was administered SC at a daily dose of 25 mg/kg. The therapy was started 100 days after the tumor transplantation and continued for 60 days. Tumor weights and volumes were significantly reduced in rats treated with microcapsules or flutamide alone, but the former drug inhibited tumor growth more than the latter. The combined treatment of flutamide and microcapsules significantly decreased tumor weight and volume, but did not exert a synergistic effect on tumor growth, the reduction being smaller for the combination than for the microcapsules alone. There was a significant elevation of serum testosterone, LH, and prolactin in rats treated with flutamide. On the other hand, in rats given microcapsules of D-Trp-6-LH-RH, testosterone fell to castration levels within 7 days and remained at nondetectable values, serum LH and prolactin levels being also suppressed in this group. The combined administration of microcapsules and flutamide also significantly decreased serum testosterone to nondetectable levels by day 7 and suppressed serum LH and prolactin. Our findings raise doubts of whether the daily administration of the combination of LH-RH agonist with an antiandrogen offers an advantage over the use of microcapsules of an agonist like D-Trp-6-LH-RH alone in the treatment of prostatic carcinoma.
...
PMID:Investigation of the combination of the agonist D-Trp-6-LH-RH and the antiandrogen flutamide in the treatment of Dunning R-3327H prostate cancer model. 315 27

The effect of combining hormonal treatment consisting of long-acting microcapsules of the agonist [D-Trp6]LH-RH (the D-tryptophan-6 analog of luteinizing hormone-releasing hormone) with the chemotherapeutic agent cyclophosphamide was investigated in the Dunning R-3327H rat prostate cancer model. Microcapsules of [D-Trp6]LH-RH formulated from poly(DL-lactide-co-glycolide) and calculated to release a controlled dose of 25 micrograms/day were injected intramuscularly once a month. Cyclophosphamide (Cytoxan) (5 mg/kg of body weight) was injected intraperitoneally twice a week. When the therapy was started 90 days after tumor transplantation--at the time that the cancers were well developed-and was continued for 2 months, tumor volume was significantly reduced by the microcapsules or Cytoxan given alone. The combination of these two agents similarly inhibited tumor growth but did not show a synergistic effect. In another study, the treatment was started 2 months after transplantation, when the developing tumors measured 60-70 mm3. Throughout the treatment period of 100 days, the microcapsules of [D-Trp6]LH-RH reduced tumor volume more than Cytoxan did, and the combination of the two drugs appeared to completely arrest tumor growth. Tumor weights also were diminished significantly in all experimental groups, the decrease in weight being smaller in the Cytoxan-treated group than in rats that received the microcapsules. The combination of Cytoxan plus the microcapsules was 10-100 times more effective than the single agents in reducing tumor weights. In both experiments, testes and ventral prostate weights were significantly diminished, serum testosterone was suppressed to undetectable levels, and prolactin values were reduced by administration of microcapsules of [D-Trp6]LH-RH alone or in combination with Cytoxan. These results in rats suggest that combined administration of long acting microcapsules of [D-Trp6]LH-RH with a chemotherapeutic agent, started soon after the diagnosis of prostate cancer is made, might inhibit the proliferation of androgen-dependent and -independent cells, improve further the therapeutic response, and increase the survival rate.
...
PMID:Combination of long-acting microcapsules of the D-tryptophan-6 analog of luteinizing hormone-releasing hormone with chemotherapy: investigation in the rat prostate cancer model. 315 90

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