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)

Ten patients with previously untreated prostatic carcinoma were studied to evaluate the hormonal effects of different doses of estramustine phosphate (Estracyt). The drug was given by mouth in increasing doses; during the first month 70 mg daily, during the second 140 mg, during the third 280 mg and during the fourth and following months 560 mg. The following hormonal parameters were studied before the treatment and then once weekly during a period of four months: testosterone, dihydrotestosterone, androstenedione, cortisol, FSH and LH. The levels of the steroids were also re-assessed one to two years later. The patients were also followed clinically at regular intervals. Initial testosterone levels of approximately 20 nmol/l plasma were reduced to approximately 0.6 nmol/l already by the lowest Estracyt dose of 70 mg/day. No further decrease was obtained by a stepwise increase of doses up to 560 mg/day. The plasma levels of dihydrotestosterone, androstenedione, FSH and LH were also reduced significantly following the administration of the lowest daily Estracyt dose and then remained at that low level. Cortisol levels increased steadily during the four months of the study. After longterm treatment the hormonal indices were by and large the same as during the last initial treatment period. Initially, the clinical effect of the treatment was excellent. In 4 patients, however, the therapy had to be discontinued after some time, because of complicating oedema (2 patients) or refractoriness to therapy (2 patients). Three years after initiating the therapy 6 patients still were on Estracyt treatment. All of them were doing well subjectively. In 5 patients the prostatic cancer was in remission or at least stable. In one patient, however, skeletal metastases were progressing. In conclusion, Estracyt was found to possess a maximal hormonal (oestrogenic) effect already in doses far below those usually recommended.
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PMID:Hormonal effects of different doses of estramustine phosphate (Estracyt) in patients with prostatic carcinoma. 678 1

The 24-hr mean plasma concentrations of 13 hormones or hormone metabolites (cortisol, testosterone, dihydrotestosterone, dehydroisoandrosterone, dehydroisoandrosterone sulfate, androsterone, androsterone sulfate, estrone, thyroxine, triiodothyronine, LH, FSH, and prolactin) were measured in 16 rigorously screened patients (aged 55-80) with stage C or D prostate cancer and 36 normal men. Nine of the hormones showed no abnormalities in the patients but four (testosterone, dihydrotestosterone, cortisol, and estrone) showed abnormalities. Testosterone and dihydrotestosterone, which, respectively, decreased with age and showed no change with age in the normal men, rose sharply with age in the patients. The patients' curves crossed the normal curves at about age 65; patients 65 or above showed normal values while patients under age 65 showed significantly subnormal levels of both hormones: testosterone averaged 282 ng/dl in patients vs 434 ng/dl in controls (P less than 0.0001) and dihydrotestosterone averaged 70 ng/dl in patients vs 99 ng/dl in controls (P less than 0.01). Cortisol, which was age invariant in the normal men, fell sharply with age in the patients; patients under 65 had significantly elevated levels (10.1 vs 6.9 micrograms/dl; P less than 0.0001), while patients 65 or older had normal levels. Estrone levels were age invariant in both patients and controls, but the mean level in patients was markedly elevated (81 vs 47 pg/ml in controls; P less than 0.001). The cortisol/testosterone ratio almost completely separated prostate cancer patients under 65 from normal men, but did not discriminate patients 65 or older from normal. The findings indicate that prostate cancer patients under 65 differ markedly in their endogenous hormonal pattern from patients 65 or older. This leads us to propose a "two-disease" theory of prostate cancer, with possible differences in genetic factors and prognosis.
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PMID:Abnormal levels of plasma hormones in men with prostate cancer: evidence toward a "two-disease" theory. 715 90

Androgen-binding protein (ABP) appears to originate in the Sertoli cells, which are stimulated by FSH and androgens, and serves to transport androgen into the lumen of the seminiferous tubules. Androgen may be more readily available for the process of spermatogenesis and sperm maturation. ABP was measured in rabbit and human testes using the method of polyacrylamide gel electrophoresis described by Ritzen et al. (1974). The values of ABP were as follows: rabbit testes (n=6) 0.44 +/- 0.05 pmoles/mg protein, rabbit caput epididymides (n=5) 5.52 +/- 1.4 pmoles/mg protein, rabbit corpus epididymides (n=5) 1.35 +/- 0.43 pmoles/mg protein, rabbit cauda epididymides (n=5) 0.39 +/- 0.12 pmoles/mg protein, rabbit efferent duct fluid (n=2) 62.4 +/- 24.6 pmoles/mg protein and human testes (obtained from untreated patients with prostatic cancer)(n=3) 0.30 +/- 0.22 pmoles/mg protein. Since we could not distinguish ABP from testosterone-estrogen binding globulin (TeBG) with the assay, the values were corrected at first by Hb concentration, but it was not satisfactory, and other methods are now being studied.
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PMID:[Studies of androgen binding protein. 1st report: Androgen binding protein in testis and epididymis of rabbit and human (author's transl)]. 719 99

In 32 subjects with histologically and/or cytologically verified prostatic cancer the hormonal pattern was studied by assaying 18 plasma and urinary hormones or groups of hormones. The tumours were classified according to the UICC classification system and the hormone values were correlated to the local extent of the tumour (T classification), the presence of metastases (M classification) and the differentiation of grade (G classification). It was found that patients with metastases had significantly higher plasma oestradiol and lower testosterone/oestradiol and testosterone/oestrone plus oestradiol ratios as compared to those subjects without metastases. In subjects with moderately or poorly differentiated tumours plasma oestrone + oestradiol was significantly higher and the testosterone/oestrone + oestradiol ratio was significantly lower than in the subjects with well differentiated tumours. In the various TNM classification groups no obvious trends were found with regard to urinary hormones and no significant differences between the groups for plasma FSH, LH, prolactin, progesterone and cortisol were observed. It is concluded that in more advanced cases with metastatic cancer and when tumours are less well differentiated the androgen/oestrogen ratio may be decreased. These alterations have no diagnostic significance because of greater overlapping of individual results between the various groups of patients.
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PMID:Hormonal pattern in prostatic cancer. I. Correlation with local extent of tumour, presence of metastases and grade of differentiation. 730 85

Researchers compared data on 91 men who had undergone vasectomy at least 10 years earlier with data on 91 healthy men matched for age, weight, height, and neighborhood who had not undergone vasectomy to examine whether the link between vasectomy and prostate cancer is based on changes in serum hormone levels. All the men lived in suburban Xiangtan in Hunan Province, China. Cases had a higher mean serum dihydrotestosterone level than controls (1.18 vs. 1.05 nmol/l; p 0.05). Yet men who had undergone vasectomy less than 20 years earlier not only had a higher dihydrotestosterone level than age-matched controls (1.46 vs. 1.22 nmol/l; p 0.01) but had a lower testosterone/dihydrotestosterone ratio (14.5 vs. 20.1; p 0.005). On the other hand, men who had undergone vasectomy more than 20 years earlier had a higher testosterone level than age-matched controls (27.2 vs. 23.9 nmol/l; p 0.05). Men who had undergone vasectomy when they were less than 35 years old had a higher FSH level and those who were 35-39 years old at vasectomy had a higher dihydrotestosterone level than age-matched controls (19.5 vs. 14.8 mIU/ml and 1.31 vs. 1.09 nmol/l) (p 0.05). Even though men who were at least 40 years old at vasectomy had a higher dihydrotestosterone level than matching controls (1.24 vs. 1.09 nmol/l), the difference was not statistically significant. These findings suggest that vasectomy may cause a reduction in testosterone levels by minimizing the conversion from testosterone to dihydrotestosterone in the long term. Thus, they support the hypothesis that a long-term effect of vasectomy may be an elevated risk of prostate cancer. More research is needed to confirm or refute this hypothesis.
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PMID:Early and late long-term effects of vasectomy on serum testosterone, dihydrotestosterone, luteinizing hormone and follicle-stimulating hormone levels. 886 15

Antiandrogens have sporadically been reported to exert antitumor activities in both pre- and post-menopausal breast cancer. To explore the possibility of using the pure antiandrogen flutamide (FLU) in breast cancer therapy, rats bearing DMBA-induced mammary tumors were treated with FLU, dihydrotestosterone (DHT), or FLU plus DHT. FLU was administered orally, at doses comparable to those used in the treatment of prostate cancer patients. FLU-treated animals had a significantly smaller average tumor area than controls from day 11 up to the end of the experiment (day 20). A similar reduction of tumor growth was observed in rats given DHT and in those treated with DHT plus FLU. Plasma levels of LH, FSH, P, 17-OH P, E2 and DHEA measured at the end of experiment did not differ between treated animals and controls. Results demonstrate that the antiandrogen FLU and the full androgen DHT exert similar inhibitory effects on the growth of dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumors. Moreover, data show that plasma steroids levels are unaffected by FLU treatment. This finding rules out any antitumor effect dependent on the reduction of adrenal and gonadal steroidosynthesis, and makes it appear more likely that androgen receptors are involved in the antiproliferative effect of FLU.
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PMID:Growth inhibition of DMBA-induced rat mammary carcinomas by the antiandrogen flutamide. 771 86

We report here the influence of intratesticular aromatase activity and intratesticular estrogen concentration on spermatogenesis. In the present study, we measured the levels of aromatase activity and the concentrations of intratesticular testosterone (T) and estradiol (E2) in 21 testicular tissues from biopsy of 20 idiopathic male infertility patients, 5 testicular tissues from castration of 4 prostatic cancer patients and a testicular tissue from an autopsy. Serum T, Free T, E2, LH and FSH were also measured if possible. Aromatase activity in the testis were assayed by measuring the amount of 3H2O formed during the conversion of [1 beta-3H] androstenedione to estrogen. Histological evaluation of the testes were performed using the Johnsen's score count (JSC) method. The rate of aromatase activity was linear in regard to time and amount of tissue. The production of 3H2O was inhibited by 4-hydroxyandrostenedione. The apparent Km (Michaelis constant) of the reaction was 23.2 nM. The rate of aromatase activity increased linearly as JSC level decreased (r = 0.67). Also, it significantly correlated with intratesticular T (r = 0.69), E2 (r = 0.88) and T/E2 ratio (r = -0.85), whereas it was not correlated with serum T, free T, E2, T/E2 ratio and free T/E2 ratio. Therefore, our results suggest the possibility that the increase in the rate of aromatase activity and the concentration of E2 may influence spermatogenesis.
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PMID:[A study on intratesticular aromatase activity in male infertility]. 777 64

In view of the multifactorial nature of the endocrine dysfunctions that may develop during prostate cancer and the unsuitability of the most widely used statistical methods to study such dysfunction, we have in the present study examined the relationships among 17 biological variables in 26 patients with advanced prostate cancer by two complementary multivariate methods, correspondence factorial analysis (CFA) and a hierarchical automatic classification procedure. The 17 variables included 14 hormones, their precursors or metabolites [LH, FSH, estradiol (E2), testosterone, dihydrotestosterone (DHT), androstenedione (A), androstenediol (Ediol), dehydroepiandrosterone (DHA), DHA-sulphate (DS), cortisol (CORT), 17 alpha-hydroxyprogesterone (17-OH-PROG), pregnenolone (PREG), 17 alpha-hydroxypregnenolone (17-OH-PREG), and androstanediol glucuronide (ADG)], one plasma binding protein, namely, sex-hormone-binding protein (SHBG) and two tumour markers, prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA). The originality of these multivariate methods is that they do not preselect a dependent variable nor perform two-by-two correlations as in stepwise multiple regression analysis but describe the patient population by extracting layers of correlations (from strong to weak) from amid confounding variables. Compared to principal component analysis which is based on covariance, CFA, based on the chi 2-metric, enables the licit representation of both tests and patients on the same factorial maps. From an examination of proximity among variables, it is possible to deduce which tests are related, which groups of patients have similar hormone profiles, and which tests vary most in which patients. The most discriminant factors in this particular population of patients were PSA and PAP levels, which were, however, not strongly correlated and were apparently selectively associated with certain hormones. PAP seemed the more pathological marker; PSA was somewhat anticorrelated to the adrenal androgen (DHA and DS) and PREG levels. The hormones with the lowest variance were A, Ediol and CORT reflecting their key roles in metabolism. A number of patients were hypogonadic. SHBG levels were not closely related to total T levels but anticorrelated with ADG suggesting that, in the patients concerned, SHBG decreases the bioavailable T fraction. There was no correlation between ADG and precursor hormones (PREG, DHA, DS) but a slight anticorrelation between these precursors and DHT. Therefore the source of ADG in these patients does not seem to be increased levels of precursor hormones nor of DHT but increased peripheral tissue metabolism of androgens. In future, descriptive multivariate analyses of large patient cohorts should help to define subpopulations with distinctive hormone profiles for prospective clinical studies.
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PMID:A multivariate approach to the description of patient populations. An example of the analysis of the hormone profiles of patients with advanced prostate cancer. 866 66

Prostate epithelial cell growth is under the control of both steroid and peptide factors. Human prostate cancer cell lines have been used to investigate similar agents in malignancy. Activins are dimeric peptides structurally related to transforming growth factor-beta and produced in the gonads and a wide array of extragonadal tissues. The activins act at the pituitary to regulate the synthesis and secretion of FSH. At other sites, such as bone marrow, liver, and gonads, activin may play an important role in the regulation of cell growth and differentiation. It was the purpose of the current study to determine whether activin had similar actions on prostate cancer cells, specifically the androgen-responsive LNCaP and the androgen-resistant PC-3 cell lines. Using reverse transcription-PCR, messenger RNAs for type I and type II activin receptor subunits as well as the activin-binding protein follistatin were detected in both cell lines. Activin treatment rapidly (<24 h) inhibited LNCaP, but not PC-3, cell growth. The effects of activin were evident at low levels, with a concentration of 5 ng/ml being effective at 24 h, and a concentration of 0.5 ng/ml being effective at 48 h. These results contrasted with the actions of transforming growth factor-beta, which inhibited only PC-3 cells and required a greater treatment duration (96 h) to be effective. To determine whether these prostate cancer cell lines were also producing activin, LNCaP and PC-3 cells were treated with follistatin. Again, only the LNCaP cells responded, with growth acceleration noted by 24 h. As PC-3 cell responses to activin could be independent of cell proliferation, we transfected LNCaP and PC-3 cells with a known activin-responsive promoter/reporter gene construct (p3TP-Lux) and treated cells with activin. Only LNCaP cells produced a measurable response in luciferase activity. Finally, we attempted to determine whether the PC-3 cell resistance to activin was mediated via a transferable factor. PC-3 conditioned medium was added to LNCaP cells in the absence or presence of exogenous activin and had a small, but statistically nonsignificant (P < 0.09), action to blunt the actions of activin. We conclude that activin is a potent growth inhibitor of LNCaP cell growth. Moreover, these cells also produce activin, suggesting that locally derived activin may play a role in regulating cell proliferation. Despite expressing messenger RNAs for activin receptors, PC-3 cells are resistant to activin, perhaps the result of the production of an activin-blocking factor or a defective activin response system. These cell lines will thus serve as useful models in which to further study the cellular basis of activin action.
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PMID:Activin inhibition of prostate cancer cell growth: selective actions on androgen-responsive LNCaP cells. 894 Mar 39

Treatment of prostatic cancer with GnRH agonist is a medical alternative to surgical castration, although hyperstimulation of the tumor can occur. We describe an unusual unwanted effect of such a treatment which unmasked a clinically silent gonadotroph adenoma. A 62-year-old man developed after the first injection of leuprorelin-depot a sudden intracranial hypertension, which was related to apoplexy of an unknown pituitary adenoma. Its gonadotroph origin was recognized after surgery by immunocytochemistry. Retrospectively, the tumor was shown to secrete in vivo both FSH and LH when on therapy with the agonist, demonstrating the lack of desensitization. Testosterone levels were also markedly and sustainly high when on therapy, a particularly unwanted effect in prostatic cancer. As gonadotroph adenomas occur in men in the same age group as prostatic cancer, the question is raised whether hormonal testing and pituitary imaging should be performed before starting a therapy with GnRH agonist in men.
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PMID:Pituitary apoplexy of a gonadotroph adenoma following gonadotrophin releasing hormone agonist therapy for prostatic cancer. 941 12


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