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)

Since Prolactin has intra- and extrapostatic effects on growth and function of the prostate, the influence of the anti-prolactin bromocriptine (PRAVIDEL) was investigated in 15 patients with untreated prostatic carcinoma of various grades of differentiation in vivo. A five-days treatment with 15 mg Pravidel daily significantly suppressed prostatic androgen uptake, unrelated to tumor grading. 5 alpha-Reductase was favored in poorly differentiated lesions with a decreased testosterone/dihydrotestosterone ratio. The pretherapeutic accumulation of 5 alpha-androstanediol was diminished after Pravidel and the tissue/plasma ratio decreased. The 17 beta-hydroxy-pathway of testosterone is predominant as compared to the 17-keto pathway; both pathways are favored after Pravidel in poorly differentiated tumors. Intraprostatic metabolic effects of Pravidel are not related to peripheral androgen levels nor are they dependent on altered prostatic hormone uptake. In the poorly differentiated prostatic tumors Pravidel initiates a metabolic situation as observed in prostate cancer responding to androgen depletion or estrogen therapy.
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PMID:[Bromocriptine and prostatic carcinoma: testosterone metabolism in relation to tumor grading (author's transl)]. 43 16

The serum levels of the pineal hormone melatonin were determined by radioimmunoassay (RIA) in 4-h intervals throughout a 24-h period in elderly men with different types of prostate tumors: benign prostatic hyperplasia (BPH, n = 13), incidental carcinoma (PCi, n = 5), and nonmetastasizing carcinoma (PC, n = 9), as well as in young men (YM, n = 10). Simultaneously, the pituitary hormones prolactin, growth hormone, luteinizing hormone and follicle-stimulating hormone were measured by RIA. All subjects were untreated and free of serious complaints, and they stayed in the same environment. The data were analyzed by the population mean-cosinor method, and linear correlation coefficients between the five hormones were calculated for each group. Melatonin showed significant circadian rhythms in young men and patients with BPH and PCi but not in patients with PC. Twenty-four-hour mean concentration (mesor) and amplitude were significantly increased in patients with PCi as compared to patients with PC. Prolactin showed significant circadian rhythms in young men and in patients with BPH, whereas patients with PCi and PC appeared to have ultradian variations. Growth hormone did not show significant rhythms in any of the groups; the mesors were elevated in all tumor groups as compared to young men. Gonadotropin mesors were elevated in all tumor patients as compared to young men; rhythms were not detected. Carcinoma patients showed different interhormonal correlations than all other groups. These results indicate that modulation of melatonin secretion, accompanied by changes in the pituitary hormone levels, may be related to development and growth of prostate cancer.
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PMID:Evidence for modulation of melatonin secretion in men with benign and malignant tumors of the prostate: relationship with the pituitary hormones. 242 Sep 60

Pretreatment plasma concentrations of total testosterone, prolactin, and total estradiol-17 beta (E2) were measured in 123 prostatic cancer patients who were categorized into groups according to the UICC classification. Patients with intracapsular tumour without metastases had significantly higher (p less than 0.05) pretreatment total estradiol levels than those with more advanced disease. The patients were treated either by orchiectomy or estrogens. The mean follow-up time was 48 months. Higher pretreatment estradiol and testosterone levels were associated with better survival. Prolactin assays seemed to be of no value in this respect.
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PMID:Pretreatment hormone levels in prostatic cancer. 318 1

The concentration of unoccupied prolactin binding components was measured in 11 prostatic malignant tissue specimens obtained by TURP. Prolactin labeled with 125I binds specifically to mitochondrial and microsomal membrane subcompartments in some well- and medium-differentiated prostate cancer structures (67 and 50% of tumors, respectively). All the examined low-differentiated prostatic cancers (4/4) were found to be receptor-poor tissues. Thermal stability of prolactin binding components in tissues stored for 45 days at -30 degrees C is satisfactory and apparently is significantly greater than that of prostatic androgen receptors.
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PMID:Prolactin binding components in prostatic cancer tissue specimens obtained by TURP. 325 5

Hypophysectomy was studied for its possible effects on cancer by alt eration of the endorcines at the New York Hospital-Cornell Medical Center beginning in 1953. The major effort has been the treatment of 850 cases of metastic breast cancer. In 80 patients with other types of metastatic cancer benefit was found only in 50 cases of prostatic cancer. Prolactin is mediated directly from the anterior pituitary to breast tissue where it aids and abets the growth of breast cancer; its secretion is largely dependent on the estrogen produced in ovaries and adrenals. In humans estrogen given after total hypophysectomy is found to be ineffective in altering metastases. Growth hormone is also produced in the anteriod lobe of the pituitary but its production is not dependent on an estrogen feed-back mechanism. If the primary cancer is dependent on the presence of prolactin, failures with hypophysectomy are explained the tumor having gained autonomy and being no longer so dependent. Contraindications to hypophysectomy include extensive pulmonary, liver, or brain metastases and any systemic disease that would preclude major surgery. Following a remission after oophorectomy, another remission with hypophysectomy may often be obtained. Neither the pathological type of a breast cancer nor the location of metastases alter the results. However the longer the interval between mastectomy and reactivation of the tumor, the more favorable the outlook. Maintenance substitution therapy following removal of the pituitary employs daily hydrocortisone, 17.5 mg orally, or equivalent steroid preparations. The mortality rate is 2% in the first 30 days after operation. In 88 patients evaluated 2 years after operation those who had received a remisssion lasting over 6 months survived nearly 5 times longer than those unbenefitted by the operation. The intracranial procedure is preferred. In cases of failure or when a remission terminates, male hormone therapy, chemotherapy, or radiation may have limited value.
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PMID:Hypophysectomy for metastatic cancer. 466 60

To investigate the possible role of circulatory levels of prolactin on the development of prostatic tumors, and to gain insight into the prolactin-androgen relationship, serum prolactin and testosterone were determined in 73 patients with newly diagnosed prostatic adenocarcinoma. Controls consisted of 32 patients with benign prostatic hyperplasia before treatment, 19 age-matched controls, and 21 young individuals. Hormones were measured under standardized conditions by highly specific and sensitive radioimmunoassays. There was no difference in prolactin in the elderly men regardless of prostate pathology, but a significant increment was found in young controls. Individual prolactin values did not correlate with serum testosterone, and there was no statistical regression in prolactin values of patients in the age range between 50 and 80 years. In a second study, serum testosterone and prolactin were measured in 7 patients with prostate cancer and in 6 individuals with benign prostatic hyperplasia before and 30 and 60 minutes after stimulation with an iv bolus of 200 microgram TRH. Both hormones were within the normal range at time T0, and a significant stimulation of prolactin was achieved (p less than 0.001). Prolactin values did not differ between patients with benign and malignant prostatic disease. Thus, when investigating the role of prolactin in neoplastic prostatic growth in the human, it seems necessary to investigate receptor-mediated prostatic tumor responsiveness, and interferences with androgen converting enzymes on a cellular level, rather than circulating prolactin concentrations.
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PMID:Serum prolactin and tumors of the prostate: unchanged basal levels and lack of correlation to serum testosterone. 615 29

Plasma prolactin was measured in 10 patients with prostatic cancer during treatment with cyproterone acetate (300 mg/week i.m.) Prolactin was assayed during a six month period at weekly intervals during the first 4 weeks and then at monthly intervals. Orchiectomy was not carried out. After 6 months prolactin levels were elevated compared with pre-treatment levels. It is concluded from this study that cyproterone acetate interferes with prolactin secretion by the pituitary gland.
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PMID:Effect of cyproterone/acetate (SH-714) on plasma prolactin in patients with prostatic cancer. 645 45

Citrate production is a major physiological function of the prostate that is regulated by testosterone and prolactin. Mitochondrial aspartate aminotransferase (mAAT) is a key enzyme in the metabolic pathway of prostate citrate production. In addition, prolactin stimulates expression of mAAT in the rat lateral prostate. In this report we establish the role of prolactin in the regulation of mAAT in two prostate cancer cell lines, LNCaP and PC-3. LNCaP cells respond to hormonal stimulation with increased secretion of prostate specific products. PC-3 cells, on the other hand, are testosterone independent and apparently do not respond to other growth factors either. Results showed that both LNCaP and PC-3 cells responded to prolactin with increased mAAT activity and an increased steady state level of mAAT mRNA. Prolactin also increased protein kinase C (PKC) activity in both these cell lines. Treatment of LNCaP and PC-3 cells with the phorbol ester 12-O-tetradecanoylphorbol (TPA) caused the same effect on mAAT activity and mRNA level as prolactin. The results suggest that the diacylglycerol-PKC signal transduction system mediates the prolactin effect on mAAT. In addition, these results also show that the prolactin effect on mAAT is independent of androgens since PC-3 cells reportedly lack androgen receptor expression. Thus, these results provide evidence that prolactin is a physiological regulator of prostate function in human as well as rat prostate. In addition, the results also show that though prostate cancer cells are androgen independent, they remain responsive to prolactin. This could have important implications for the treatment and management of prostate cancer.
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PMID:Prolactin regulation of mitochondrial aspartate aminotransferase and protein kinase C in human prostate cancer cells. 909 97

Prolactin is an important physiological regulator of prostate development and growth in preclinical models. In prostate cancer there is strong evidence that prolactin exerts a trophic effect independent of testosterone. In addition, patients with prostate cancer that have an elevated prolactin level correlated with a poorer prognosis. Based on these data, we evaluated the clinical effect of prolactin suppression using bromocriptine in patients with androgen-independent prostate cancer. We conducted an open-label phase II trial of bromocriptine in patients with progressive metastatic prostate cancer. Basal and thyrotropin releasing hormone (TRH)-stimulated prolactin levels were utilized as biological endpoints for determining the dose of bromocriptine. All patients continued to receive complete androgen blockade. Thirteen patients were enrolled (median age 69.5 years). There were no complete or partial responses associated with bromocriptine in 11 of the evaluable patients. The mean duration of bromocriptine treatment was 8.2 weeks (2-14 weeks). One patient had a clinically insignificant decrease in prostate-specific antigen (PSA) and another patient had a 19.9% decrease in PSA with progression of a soft tissue mass. The vast majority of patients (10 of 11) had suppression of prolactin with a bromocriptine dose of 2.5 mg three times a day. One patient required a dose adjustment due to inadequate suppression, with a final maintenance dose of bromocriptine 12.5 mg per day resulting in complete suppression. No serious treatment-related toxicities were observed. The most common complications noted were nausea, headaches, dizziness, and fatigue. Our data showed that 2.5 mg three times per day of bromocriptine suppressed prolactin in 90% of the patients. Furthermore, this dose appears to be well tolerated.
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PMID:A phase II study of bromocriptine in patients with androgen-independent prostate cancer. 962 40

Prolactin stimulates citrate accumulation in prostate cells by increasing the expression of mitochondrial aspartate aminotransferase (mAAT). In this study, we further investigated the mechanism of prolactin regulation of mAAT expression in rat lateral prostate and LNCaP and PC-3 prostate cancer cells. Prolactin and 12-O-tetra-decanoylphorbol 13-acetate (TPA) increased the mAAT mRNA level twofold to fourfold. In addition, prolactin and TPA increased protein kinase C (PKC) activity in prostate cells 20% to 60% and 40% to 210%, respectively. The effects of both prolactin and TPA on mAAT mRNA were eliminated by downregulation of PKC. The effect of prolactin and TPA on gene transcription was determined using mAAT-chloramphenicol acetyltransferase (CAT) reporter-gene constructs, transiently transfected into PC-3 cells. The 59 untranslated region of the precursor form (pmAAT) of the mAAT gene contains five sequences that are homologous to the consensus TPA response elements (TRE). Reporter constructs with various combinations of these sequences were used to assay prolactin stimulation of CAT transcription in PC-3 cells. Prolactin increased CAT expression in PC-3 cells transfected with a reporter gene containing four of the TRE consensus sequences. Another CAT reporter gene, which contained two of the putative TREs, was also stimulated by prolactin, but a third reporter, containing the two other TRE sequences, was not induced by prolactin. These results suggest that prolactin regulates mAAT at the transcriptional level. Moreover, because both prolactin and TPA induced PKC activity, and because the effects of prolactin and TPA were eliminated when PKC was downregulated, we postulate that the prolactin effect on mAAT expression is mediated via the diacylglycerol PKC signal transduction pathway in rat lateral prostate and human prostate cancer cells.
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PMID:Protein Kinase C Mediates Prolactin Regulation of Mitochondrial Aspartate Aminotransferase Gene Expression in Prostate Cells. 1085 Dec 92


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