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)

LH-releasing hormone (LHRH) agonists exert a direct inhibitory action on the growth of both androgen-dependent (LNCaP) and androgen-independent (DU 145) human prostatic cancer cell lines. The present studies were aimed at clarifying whether these compounds might exert their antiproliferative action by interfering with the stimulatory action of epidermal growth factor (EGF). To this purpose, the effects of a LHRH agonist (Zoladex, LHRH-A) on the mitogenic action of EGF, on some of the EGF-activated intracellular signaling mechanisms (tyrosine phosphorylation of the 170-kDa EGF receptor, and c-fos protooncogene expression), as well as on the concentration of EGF receptors have been evaluated. These studies have been performed in both LNCaP and DU 145 cells. The results obtained show that in LNCaP cells, LHRH-A counteracts the mitogenic action of EGF, completely abrogates EGF-induced c-fos expression, and significantly reduces the concentration of EGF-binding sites. The EGF-activated tyrosine phosphorylation of the EGF receptor is not affected by LHRH-A in LNCaP cells. In DU 145 cells, LHRH-A antagonizes the proliferative action of EGF, inhibits the tyrosine phosphorylation of the EGF receptor induced by EGF, and significantly reduces the number of EGF-binding sites. In these cells, LHRH-A is not able to modify the increased expression of c-fos that follows the treatment with EGF. These data suggest that LHRH agonists may inhibit the proliferation of human prostatic tumor cells by interfering with the stimulatory actions of EGF. The intracellular mechanism of action of these compounds appears to differ in androgen-dependent LNCaP and androgen-independent DU 145 cells.
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PMID:Luteinizing hormone-releasing hormone agonists interfere with the stimulatory actions of epidermal growth factor in human prostatic cancer cell lines, LNCaP and DU 145. 892 40

40 male patients with metastatic prostate cancer given a choice of medical castration with the LHRH Analogue Goserelin (Zoladex) or surgical castration chose medical treatment. During a 15 month follow up only one patient decided to have an orchidectomy and this was because of treatment expense.
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PMID:Patient treatment preference in metastatic prostate cancer. 898 72

Luteinizing Hormone Releasing Hormone (LHRH) agonists exert both "in vitro" and "in vivo" a direct inhibitory action on the growth of both androgen-dependent (LNCaP) and androgen-independent (DU 145) human prostatic cancer cell lines. The present experiments have been performed to investigate the mechanisms involved in this direct antiproliferative action of LHRH agonists. In particular, the aim was to study whether these compounds might exert their antiproliferative effect by interfering with the stimulatory action of epidermal growth factor (EGF) both "in vitro" and "in vivo". To this purpose, the effects of LHRH agonist, Zoladex (LHRH-A), on the mitogenic action of EGF, on EGF-activated intracellular signaling mechanisms (tyrosine phosphorylation of EGF receptor and c-fos proto-oncogene expression), and on the concentration of EGF receptors have been evaluated in both LNCaP and DU 145 cells. The results of these "in vitro" studies show that in LNCaP cells LHRH-A counteracts the mitogenic action of EGF, abrogates the EGF-induced c-fos expression and reduces the concentration of EGF-binding sites, without modifying the EGF induced tyrosine phosphorylation. In DU 145 cells, LHRH-A antagonizes the proliferative action of EGF, inhibits tyrosine phosphorylation of EGF receptor induced by EGF and significantly reduces the number of EGF binding sites, without altering the stimulation of c-fos expression induced by EGF. For the "in vivo" experiments, male nude mice were s.c. injected in the flank with DU 145 cells and treated for 14 days with LHRH-A (100 micrograms/days). At the end of the treatment, the concentration of EGF receptors on membrane preparations as well as on tumor volume were found to be significantly lower in LHRH-A treated animals than in control mice. The mitotic index and the expression of the proliferation-associated antigen Ki67 were found similar in control as well as in treated animals. In addition no modification of apoptotic index (expression of p53) was observed. These data suggest that LHRH agonists may inhibit the proliferation of the tumor cells by interfering with the stimulatory actions of EGF.
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PMID:Effects of LHRH agonists on the growth of human prostatic tumor cells: "in vitro" and "in vivo" studies. 939 87

The aim of this study was to investigate the effect of goserelin-acetat (Zoladex) on testosterone suppression, to compare achieved suppression with clinical effects in patients with prostate cancer with bone metastases and consequent painful syndrome, to study the behavior of adiol during treatment and to assess life quality with emphases on the physical and psychological domain in relation to clinical and biological treatment effects. Fifteen patients were treated by Zoladex in one dose every 28 days, and followed-up for 12 months. All patients had several metastatic localizations in the bones, initial high prostate specific antigen (PSA), and high acid (AP) and alkaline phosphatase (ALP). PSA, testosterone, adiol (delta-5-androstenediol), luteinizing hormone (LH), foliculostimulating hormone (FSH), ALP and AP were also measured before every cycle. For evaluation of the life quality Rotterdam Symptom Checklist was used. Clinical progression was not registered during follow-up, with drop of PSA, ALP and AP. Testosterone and adiol displayed mainly inverse trends during treatment. The complete testosterone suppression was never achieved. It seems that Zoladex has quite different influence on LH and FSH, as levels of those hormones have shown opposite trend. Some of the observed hormonal effects could be attributed to stimulation of the monoamine system. Suppression of LH level provoked by administration of LHRH agonists increases level of dopamine in hypothalamus which inhibits releasing of its hormones. By inhibition of corticotropic releasing factor and ACTH, and by its influence on adrenal gland, we could explain drop of adiol levels in the first months of administration of LHRH agonists. Testosterone increase and adiol drop in the first months, and adiol increase following testosterone level drop in the fourth to eight month, may be explained by negative feed back mechanism between different androgens which could be stimulated or provoked by LHRH therapy. The question of effects which are results of LHRH agonists modulation of the monoamine system and consequent activation of other central mechanisms of hormonal regulation is still open. Patients' quality of life under therapy was improved for about 30% in psychological and functional domains. There were no significant changes on physical subscale, during treatment. It seems that the obtained positive psychological treatment effect is not only a consequence of pain decrease, but it could be the result of the change in the level of monoamines in CNS under Zoladex.
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PMID:Androgen level variations, clinical response to LHRH agonists and changes in the quality of life subscales in metastatic prostate cancer--speculations about possible role of the monoamine system. 947 91

The long-term results of external irradiation in locally advanced prostate cancer are poor: relapses are local or distant from infra-clinical disease present at diagnosis. Three clinical randomized trials have shown that hormonotherapy with LH-RH analogue with or without antiandrogen has improved: disease-free survival, local recurrence-free survival and metastasis-free survival (P < 0.001). The EORTC trial 22863 has shown a significant improvement of the overall survival (P = 0.001), with an LH-RH analogue (goserilin acetate, Zoladex) was administered the first day of irradiation and then every 4 weeks for 3 years; for the RTOG trial 85-31 the same LH-RH analogue was administered during the last week of irradiation and given until relapse increases survival of patients with poor differentiated tumours with a Gleason score ranging from 8 to 10 (P = 0.03). Adjuvant hormonal treatment with an LH-RH analogue is recommended, but the optimal duration of the treatment remains unclear.
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PMID:[Combination of radiotherapy and hormonotherapy in locally advanced cancers of the prostate]. 958 74

Experiments have been performed to clarify whether LHRH agonists might decrease growth of hormone-unresponsive prostate cancer in vivo. Male nude mice were injected s.c. with the human androgen-independent prostate tumor DU 145 cells; osmotic minipumps releasing the LHRH agonist Zoladex (LHRH-A) for 14 days were simultaneously implanted under the skin. Treatment with LHRH-A induced a significant decrease in tumor growth up to the end of the treatment. In subsequent experiment, minipumps releasing LHRH-A were implanted in nude mice either 7 or 14 days after cell inoculation. When the treatment was started 7 days after inoculation of the cells, tumor growth was significantly decreased up to 28 days; thereafter, tumor volume remained lower than in controls, although not significantly. When LHRH-A was administered beginning 14 days after cell inoculation, tumor growth was not significantly affected at any time interval considered. LHRH-A did not appear to induce apoptosis in DU 145 cells, at least on the basis of the apoptotic index and immunohistochemical staining of the p53 protein. On the other hand, treatment with LHRH-A was accompanied by a significant decrease of the concentration of epidermal growth factor receptors in DU 145 prostate cancer specimens. Our results show that the LHRH agonist used significantly inhibits the growth of DU 145 androgen-independent prostate tumor xenografts in nude mice.
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PMID:Growth-inhibitory effects of luteinizing hormone-releasing hormone (LHRH) agonists on xenografts of the DU 145 human androgen-independent prostate cancer cell line in nude mice. 959 Jan 26

There can be seen many investigations to examine the effects and benefits of total androgen blockade (TAB), combining an antiandrogen with surgical castration or a LH-RH analogue, for advanced prostate cancer. This review summarizes the concept, theory, method and clinical application of TAB. The concept of TAB was supported by reports that show a survival advantage using the combined blockade over LH-RH analogue alone. The theory of TAB proposes that suppression of all androgen production, adrenal and testicular androgen, should result in a better response than standard hormonal management such as castration and/or estrogens. In Japan, Chlormadinone acetate (100 mg twice daily) or Flutamide (375 mg three times daily) is orally administered and Leuprorelin acetate (3.75 mg every 4 weeks) or Goserelin acetate (3.6 mg every 4 weeks) is administered by hypodermic injection. There have been unresolved controversies surrounding this therapeutic modality, therefore future studies should help to define the role of TAB.
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PMID:[Total androgen blockade--concept, theory, method and clinical application]. 975 May 21

We have previously shown that LHRH agonists exert a direct and specific inhibitory action on the proliferation of the androgen-independent DU 145 prostate cancer cell line; however, the cellular mechanisms mediating this antiproliferative action are not well defined. It is well known that the insulin-like growth factor (IGF) system plays a crucial role in the local regulation of the growth of androgen-independent prostate cancer. The present experiments were performed to evaluate whether LHRH agonists might exert their antimitogenic effect by interfering with the activity of the locally expressed IGF system. To this purpose, the effects of the LHRH agonist Zoladex (LHRH-A) on 1) the mitogenic action of IGF-I, 2) the tyrosine phosphorylation of type 1 IGF-I receptor (IGF-IR), 3) the concentration of IGF-IR, and 4) the secretion of IGF-binding protein-3 were studied. The results obtained show that in DU 145 cells, LHRH-A 1) counteracts the mitogenic action of IGF-I in a dose-dependent manner, 2) prevents the IGF-I-induced tyrosine phosphorylation of the IGF-IR, 3) reduces the concentration of IGF-IR without affecting its Kd value, and 4) does not affect the secretion of IGF-binding protein-3 in the conditioned medium from these cells. These data suggest that LHRH agonists may inhibit the proliferation of human androgen-independent prostate tumor cells by interfering with some of the cellular mechanisms mediating the stimulatory action of the IGF system.
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PMID:Luteinizing hormone-releasing hormone agonists interfere with the mitogenic activity of the insulin-like growth factor system in androgen-independent prostate cancer cells. 988 42

Goserelin is a synthetic decapeptide analogue of luteinising hormone-releasing hormone (LHRH). For experimental purposes it has been administered subcutaneously as an aqueous solution, but for therapeutic use it is formulated as subcutaneous depots releasing goserelin over periods of 1 (3.6 mg) or 3 (10.8 mg) months. Pharmacokinetic data have been generated using a specific radioimmunoassay. When administered as a solution, goserelin is rapidly absorbed and eliminated from serum with a mean elimination half-life (t1/2beta) of 4.2 hours in males and 2.3 hours in females. The shapes of the observed serum goserelin profiles following administration of the depots are primarily determined by the rate of goserelin release from the biodegradable lactide-glycolide copolymer matrix over periods of 1 or 3 months. There is no clinically relevant accumulation of goserelin during multiple administration of these depots. Goserelin is extensively metabolised prior to excretion. Its pharmacokinetics are unaffected by hepatic impairment, but the mean t1/2beta increases to 12.1 hours in patients with severe renal impairment. This suggests that the total renal clearance (renal metabolism and unchanged drug) is decreased in patients with renal dysfunction. It is unnecessary to adjust the dose or administration interval when the depot formulations are administered to elderly patients or to those with impaired renal or hepatic function. Administration of a goserelin 3.6 mg or 10.8 mg depot results in an initial increase of luteinising hormone (LH) levels and in increases of serum testosterone or oestradiol levels in males and females, respectively. This is followed by a decrease in serum LH levels and suppression of testosterone or oestradiol to within the castrate or menopausal range, respectively. Subsequently, throughout treatment with goserelin depots, serum testosterone or oestradiol levels remain suppressed. Clinical outcomes following treatment of patients with prostate cancer, breast cancer and benign gynaecological conditions with goserelin are described briefly.
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PMID:Clinical pharmacokinetics of goserelin. 1092 49

The present study compares the relative efficacy, safety and cost of therapy of the following LH-RH agonists: buserelin acetate (Suprefact(R) Depot, Hoechst Marion Roussel), goserelin acetate (Zoladex(R) LA, Zeneca Pharma Inc.), and leuprolide acetate (Lupron(R) SR Depot, Abbott Laboratories Inc.). To support the conduct of a cost-minimization analysis in patients with advanced prostatic carcinoma their comparable efficacy and safety was first assessed using a meta-analysis technique. The absence of statistically significant differences among the 2 major end points, survival and progression-free survival was confirmed. The cost-minimization analysis for the depot formulations was conducted from the perspectives of the provincial formulary and the Ministry of Health, and considered 2 time horizons: 1 year, and mean survival time of 2.5 years. Cost differences among LH-RH agonists were sensitive to changes in dosing interval and patient survival time but, even when these parameters were varied, for a general population of patients with advanced prostate cancer, buserelin remained the most cost-saving treatment alternative among LH-RH agonists.
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PMID:Meta-analysis and economic evaluation of LH-RH agonists' depot formulations in advanced prostatic carcinoma. 1130 58


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