UMLS:C0376358 - FACTA Search

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Query: UMLS:C0376358 (prostate cancer)
59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Analogs of a potent octapeptide analog of somatostatin (SRIF) H-(D)Phe-Cys-Tyr-(D)Trp-Lys-Val-Cys-Thr(NH2) were synthesized. Aromatic substitutions for Tyr resulted in little change in inhibitory potency on growth hormone (GH) secretion in the rat. Substitutions for Val or (D)Trp resulted in analogs with diminished activity. Substitution of (D)Nal for (D)Phe increased duration of GH inhibition. Final weights of subcutaneously implanted prostate tumors (R3327) were 41% lower in rats treated with an N-terminal 4-chloro-(D)phenylalanyl analog as compared to vehicle treated controls. The analog had no effect on testicular weight or final plasma testosterone levels. SRIF analogs may represent an alternative treatment for prostate cancer that would be free of the untoward reproductive effects of other treatments (e.g. LH-RH or castration).
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PMID:Inhibition of rat prostate tumor growth by an octapeptide analog of somatostatin. 288 1

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.
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PMID:Somatostatin analogs as adjuncts to agonists of luteinizing hormone-releasing hormone in the treatment of experimental prostate cancer. 289 Jan 64

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.
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PMID:Steroid hormone concentrations in relation to patient prognosis and prostate tumour grade. 312 25

Seventy-eight patients with cytologically and/or histologically confirmed prostatic cancer were randomly allocated to orchidectomy (ORX, n = 37) or combined intramuscular and oral estrogen treatment (ESTR, n = 41). Serum levels of testosterone (T), 17 alpha-hydroxyprogesterone, dehydroepiandrosterone, dehydroepiandrosterone sulfate, total estrone (tE1; sum of unconjugated and conjugated estrone, greater than or equal to 85% estrone sulfate), cortisol, luteinizing hormone, follicle-stimulating hormone, prolactin, growth hormone, sex hormone-binding globulin (SHBG), and albumin were determined prior to treatment and 12, 24, and 36 months after initiation of treatment. Fifty patients responded to treatment or had stable disease, and 28 did not respond (12 in the ORX and 16 in the ESTR group). There was no association between pretreatment hormone or protein levels and outcome of the treatment, neither in the total material nor within either of the two treatment subgroups. Significantly higher pretreatment levels of cortisol and prolactin and significantly lower levels of T, tE1, and albumin and a significantly lower T/SHBG-ratio (index on biologically active T) were found in patients with metastatic disease, compared with the patients without metastases. There was no association between testicular or adrenal androgens, SHBG, T/SHBG, and albumin values during treatment and the clinical outcome. The differences found between metastatic and nonmetastatic disease probably simply reflect the more stressful and catabolic condition and generally poorer health in patients with disseminated malignant disease. Furthermore, the study does not lend any support to the hypothesis that indicates an important role of adrenal "rest androgen" in prostatic cancer tumor growth.
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PMID:Prognostic value of serum hormone concentrations in prostatic cancer. 321 6

Peripheral serum levels of testosterone, immunoreactive oestrogens (E2), FSH, LH, prolactin and growth hormone (hGH) and two steroid-sensitive proteins, 'pregnancy-associated alpha 2-glycoprotein' (alpha 2-PAG) and sex hormone binding globulin (SHBG), were measured in patients with prostatic cancer before treatment and after orchidectomy or during combined oral and intramuscular oestrogen treatment. Following orchidectomy, the serum levels of testosterone and E2 decreased whilst the levels of FSH and LH increased significantly. No changes were noted in the serum levels of alpha 2-PAG, SHBG or prolactin. Oestrogen treatment significantly decreased the serum levels of testosterone, FSH and LH whilst levels of alpha 2-PAG, SHBG and prolactin were increased significantly. Serum levels of hGH during oestrogen treatment were significantly higher than in patients subjected to orchidectomy. These data are at variance with the established dogma of the oestrogen/androgen balance as a physiological regulator or liver protein synthesis, and indicate that factors other than the endogenous steroids may be operative. hGH may play an important role in this respect.
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PMID:Influence of orchidectomy or oestrogen treatment on serum levels of pregnancy associated alpha 2-glycoprotein and sex hormone binding globulin in patients with prostatic cancer. 392 1

Pretreatment hormone levels were determined in 222 patients with prostatic cancer and their prognostic value assessed. The patients were grouped into yearly survival categories and only those whose cause of death was due to the disease were included in the study. Low concentrations of testosterone in plasma at the time of diagnosis related to a poor prognosis. Patients who died within 1 yr of diagnosis had the lowest mean plasma levels of this steroid. The pretreatment mean plasma testosterone concentrations were found to be higher as the survival period of the various groups lengthened. This relationship was observed both when the total data were analysed and also when the patients were subgrouped depending on clinical evidence of spread of the tumour beyond the prostatic capsule (T3) or on the presence of metastases (M1). High pretreatment plasma concentrations of luteinizing hormone were also associated with poor survival. Follicle-stimulating hormone, prolactin and growth hormone concentrations did not correlate with survival time. The indications from this study are that poor testicular function is associated with early death from prostatic carcinoma and that the measurement of blood levels of testosterone at diagnosis could provide a prognosis of subsequent life-span.
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PMID:Carcinoma of the prostate: relationship of pretreatment hormone levels to survival. 642 67

In 45 patients with newly diagnosed carcinoma of the prostate, 1509 radioimmunological assays (RIA) were done for serum testosterone (T), prolactin (PRL) and growth hormone (GH). The patients were divided into 4 groups and treated with gradually lowered doses of Fostrolin and bromocriptin. It was noted that after high doses of Fostrolin, T levels did not markedly decrease, and PRL concentrations increased manifold. Small doses of Fostrolin, however, caused a drop in T and PRL levels. In the light of the results of up-to-date investigations and of the role played by PRL in a higher incidence of prostatic tumours, employment of bromocriptin, a prolactin antagonist, in the treatment of prostatic cancer seems to be justified. Reduction of T concentration below castration level and attainment of trace PRL levels in response to small doses of Fostrolin and bromocriptin had a favourable effect on the clinical course of the malignant disease.
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PMID:The serum levels of testosterone and prolactin in patients with prostatic carcinoma treated with various doses of Fostrolin and bromocriptin. 688 85

The effects of somatostatin analogue RC-160 and bombesin/gastrin releasing-peptide (GRP) antagonist RC-3095 were evaluated in Copenhagen rats bearing the anaplastic, androgen-independent Dunning R3327-AT-1 prostatic adenocarcinoma. In the first experiment, RC-160 was given in the form of microcapsules releasing 60 micrograms/day/rat. RC-3095 was administered from implanted Alzet osmotic minipumps liberating 100 micrograms/day/rat. After 32 days, tumor volumes and weights were significantly reduced by RC-160 as compared with the control group. Tumor doubling time in rats treated with RC-160 was significantly longer than in controls. Bombesin/GRP antagonist RC-3095 also significantly reduced tumor volume after 7 days of treatment, but after 18 days the inhibition in tumor volume was no longer significant. Tumor growth was not suppressed by castration. In the second experiment, 3-mm3 fragments of Dunning R-3327-AT-1 tumor were implanted orthotopically into the prostates of Copenhagen rats in order to evaluate the survival time of animals bearing this cancer during treatment with RC-160 released from Alzet osmotic minipumps at a dose of 100 micrograms/day/rat. Treatment with RC-160 significantly (P < 0.05) prolonged the mean survival time of rats by 5.3 days as compared to control animals. In both experiments, therapy with RC-160 significantly decreased serum growth hormone or insulin-like growth factor I levels. In the first experiment, receptor assays on R-3327-AT-1 tumor membranes showed high affinity binding sites for somatostatin, bombesin, and epidermal growth factor. At the end of the treatment, receptors for epidermal growth factor were significantly down-regulated by treatment with RC-160 but not with RC-3095. The binding capacity of bombesin receptors was reduced to nondetectable levels after the treatment with RC-3095. In cell cultures, high affinity binding sites for bombesin/GRP were found on intact Dunning R-3327-AT-1 cells, but receptors for somatostatin could not be detected. Proliferation of the AT-1 cell line was significantly inhibited by antagonist RC-3095. However, no effect on tumor cell growth in vitro was observed with analogue RC-160. Our results demonstrate that somatostatin analogue RC-160 and bombesin/GRP antagonist RC-3095 can inhibit the growth of the androgen-independent Dunning R-3327-AT-1 prostatic cancer in rats, although the remission produced by RC-3095 may be of short duration due to a down-regulation of bombesin receptors. Our work suggests the merit of further investigation as to whether these analogues can induce a possible delay in relapse and prolong survival in prostate cancer.
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PMID:Inhibitory effects of somatostatin analogue RC-160 and bombesin/gastrin-releasing peptide antagonist RC-3095 on the growth of the androgen-independent Dunning R-3327-AT-1 rat prostate cancer. 790 3

Nude mice bearing xenografts of the androgen-independent human prostate cancer DU-145 were treated for 4-5 weeks with somatostatin analog RC-160 or the bombesin/gastrin-releasing peptide (GRP) antagonist RC-3095. Tumor growth in animals treated with somatostatin analog RC-160 at a dose of 100 micrograms/day s.c. was significantly inhibited within 14 days of the start of the experiment. At necropsy, in mice given RC-160, tumor weight and volume were significantly decreased compared with control mice. Treatment with RC-3095 at a dose of 20 micrograms/day s.c. also suppressed tumor growth, the inhibition being significant after 2 weeks, but the reduction in tumor volume and weight was smaller than that produced by RC-160. Therapy with RC-160 significantly decreased serum growth hormone and gastrin levels. Specific binding sites for bombesin, somatostatin and epidermal growth factor (EGF) were found in the DU-145 tumor membranes. Receptors for EGF were significantly down-regulated after therapy with RC-3095 and RC-160. The finding that somatostatin analog RC-160 and bombesin/GRP antagonist RC-3095 inhibit the growth of androgen-independent prostate tumors in mice might be of practical importance for human prostate cancer therapy.
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PMID:Somatostatin analog RC-160 and bombesin/gastrin-releasing peptide antagonist RC-3095 inhibit the growth of androgen-independent DU-145 human prostate cancer line in nude mice. 810 19

Obesity is a product of welfare. About 1/3 of our population has got excessive weight, 6 to 8% is truly obese and in 0.1% we may speak of pathologic obesity. Obesity is not only an esthetic problem, but is goes together with higher morbidity and mortality. In men with a body mass index (BMI = W (kg)/L2 (m)) of more than 35, the glucose metabolism was disturbed in 70%, the lipid spectrum had a clearly atherogenic profile, the average (free) testosterone level was significantly diminished and there was also a certain degree of hypogonadism. A short term treatment (4 to 6 weeks) based on a hypocaloric diet (400) and rich in proteins normalized the glucose metabolism in a very great number of patients, while the insulinemia fell with 40% and the lipidogram always became normal, but for the HDL-C, which showed a slight drop, while the testosterone levels became normal with a strong rise of the sex hormone binding globulin. And yet, at that very moment the patients were still definitely obese: this suggests that the metabolic disturbances are not the consequence of obesity in itself, but may be related to the dietary habits of the patients. Concerning the mechanism of hypogonadism, the cause of its disturbance seems to be situated in the hypothalamo-hypophyseal area and be characterized by a lower amplitude of LH-pulses, which are correlated with the testosterone levels. This hypothalamic disorder is however not limited to the LH-secretion, but the amplitude of growth hormone- and of ACTH-pulses is also reduced. Our study suggests that not obesity itself, but dietary factors might be responsible for the detected abnormalities. This might have important implications. Indeed, it is well known that in population groups, whose diet contains fewer calories and less fat--such as the Chinese and the Japanese--sex hormone binding globulin exists in far higher concentrations whereas free testosterone is found in a lower concentration. In these populations the prevalence of clinically obvious prostate cancer--which is androgen-sensitive--is much lower than in Western countries: it seems obvious to look for a correlation between both observations. Another remarkable phenomenon is the difference in testosterone metabolism between the Eastern and Western people; this leads us to the remarkable findings that in Asian people the same amount of androgens nearly always produces azoospermia and infertility, whereas this appears in only 2/3 of the cases among Western people.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Metabolic effects of obesity in men]. 812 79

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