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)

Most technical obstacles in performing biochemical androgen receptor assays on malignant prostatic tissue have been surmounted. The available data, while suggesting that nuclear androgen receptor content in malignant tissues may be a useful criterion in this regard, remain meager and contradictory. The authors suggest that the clinical nature of prostatic cancer, including the tendency for metastases to occur in osseous and deep lymphatic regions and the heterogeneous intermingling of benign and malignant elements in the primary tumor, may preclude the success of biochemical assays for androgen receptors to predict hormonal dependency of prostatic tumors.
 ...
PMID:Androgen receptor assays in advanced prostatic cancer. 637 68

The relationship between androgen receptor concentrations and clinical response to endocrine therapy for prostatic adenocarcinoma was investigated for 13 stage D patients. Both cytoplasmic and nuclear-androgen receptors were quantified. For nuclear androgen receptor, nuclei were isolated and treated with high ionic strength buffer (0.6 M KCl) to yield a KCl-extractable fraction; the nuclei were then treated with DNase I to yield nuclear matrices. Electron microscopy confirmed the relative nuclear purity and revealed matrix morphology. An hydroxylapatite binding assay and methyltrienolone (R1881) were used to quantify androgen receptor in cytosol, the KCl-extract and matrix preparations. Following 6 months of hormonal therapy, the clinical status of patients was re-evaluated and the patients were grouped according to disease response. The androgen receptor data obtained prior to therapy were compared for the disease response groups. The mean concentrations of cytoplasmic androgen receptor, KCl-extractable nuclear androgen receptor and nuclear matrix-bound androgen receptor, respectively, in those patients with disease progression or death (no. = 6), were 671 +/- 232, 45 +/- 17 and 119 +/- 34 fmol. per gm. of tissue +/- S.E.M., and for those with disease regression or stabilization (no. = 7), 1427 +/- 435, 193 +/- 53 and 611 +/- 92 fmol. per gm. of tissue +/- S.E.M. While cytoplasmic androgen receptor concentrations were not related to clinical status, both extractable and matrix-bound nuclear androgen receptor concentrations were significantly higher in the group which responded to hormonal therapy. These results suggest that nuclear-extractable and nonextractable androgen receptor concentrations are useful indices for the prediction of hormone-dependence of prostatic cancer.
 ...
PMID:Relationship between concentrations of extractable and matrix-bound nuclear androgen receptor and clinical response to endocrine therapy for prostatic adenocarcinoma. 653 85

The incidence of prostatic cancer is highly correlated with advanced age, and it has been suggested that changes in androgen binding may be important in age-associated alterations in growth regulatory mechanisms of prostatic epithelial cells. In this study the effects of age on androgen binding characteristics in the dorsolateral prostate glands of young and aged Copenhagen rats were determined and the binding properties in the Dunning R3327/130 subline of rat prostatic adenocarcinoma were characterized. Tritium-labeled and nonlabeled methyltrienolone analogs (R1881) were used to study the binding properties of 5 alpha-dihydrotestosterone receptor in the cytosol of tumors and prostate glands. Binding of R1881 was low but specific for the androgen receptor as shown by competition studies in which nonlabeled R1881, 5 alpha-dihydrotestosterone, and testosterone competed successfully with 3H-R1881 for binding sites, but 17 beta-estradiol and low levels of progesterone did not. In Copenhagen dorsolateral prostate, Scatchard analysis suggested a single class of binding sites. In young animals (three to five months) the average binding capacity was 10.36 fmol/mg cytosol protein with a dissociation constant (Kd) of 2.28 nmol/L. The dorsolateral prostate of aged rats (11-16 months) showed no significant difference in specific binding characteristics as compared to the younger age group. Specific binding of 3H-R1881 in R3327/130 tumor was saturable with a single class of high-affinity binding sites having an average binding capacity of 64.77 fmol/mg cytosol protein and a Kd of 2.76 nmol/L. These data show that the tumor had approximately 6.5 times the number of binding sites as did the normal Copenhagen rat dorsolateral prostate gland. However, no age-related changes were detected through 11-16 months of age in the androgen binding characteristics of normal rat dorsolateral prostate gland that could be correlated with the higher concentration of androgen binding sites in the R3327/130 tumor subline.
 ...
PMID:Androgen receptor binding characteristics in the cytosol of the rat dorsolateral prostate gland and the Dunning R-3327 prostatic adenocarcinoma. 660 63

We used three heterogeneous parental cultures of LSC-AXC rat prostate cancer cells: LSC-AXC-C/O, cells maintained on culture medium; LSC-AXC-D/O, cells maintained on culture medium containing 10(-7) M 5 alpha-dihydrotestosterone; and LSC-AXC-T/O, cells maintained on culture medium containing 10(-7) M testosterone, to isolate clonally derived cell lines. Eleven of 15 clonal cell lines were tumorigenic when inoculated into intact male AXC rats. Eight tumorigenic clonal cell lines were selected for further evaluation, and all were found to possess features characteristic of secretory epithelium, as judged by light and electron microscopy. All parental cell lines and the eight selected clonal cell lines contained cytoplasmic and nuclear androgen receptors. Total receptor content was 131 +/- 61 (S.D.), 43 +/- 32, and 274 +/- 96 fmol/100 micrograms of DNA, respectively, for C-, D-, and T-cells. The differences were significant (p less than 0.05). Androgen receptor content of young mature or senescent AXC rat ventral prostate, respectively, is 518 +/- 58 and 266 +/- 40 fmol/100 micrograms of DNA. Since chromosomal analysis established that LSC-AXC prostate cancer cells are hypotriploid, androgen receptor content per cell in C- and T-cells is indicated to be either greater than or equal to that of senescent AXC rat ventral prostate, the tissue in which the original adenocarcinoma arose. Parental and clonal cell lines contained 5 alpha-reductase activity. There were significant differences (p less than 0.05) in both total reductase activity and metabolite distribution. Consequently, the intracellular content of testosterone metabolites was cell line specific. All characterized cell lines contained a higher concentration (p less than 0.05) of APase activity than did young mature or senescent AXC rat ventral prostate. In 6 of 11 cell lines, prostate-secretory APase concentration exceeded (p less than 0.05) that of AXC rat ventral prostate. However, the relative content of secretory APase compared to total APase in carcinoma cells consistently was less (p less than 0.05) than that of AXC rat ventral prostate. These studies document the establishment of clonal AXC rat prostate adenocarcinoma cell lines which have retained important morphological and phenotypic markers characteristic of differentiated prostate epithelium. Since these cells are tumorigenic and represent a spectrum of retained differentiated phenotypic markers, they should be particularly useful for in vivo and in vitro studies of hormonal regulation of prostate cancer cell behavior.
 ...
PMID:Biochemical and morphological characterization of clonal AXC rat prostate cancer cells. 671 98

Within urological practice, three important types of cancer seem to be under endocrine influence or develop in endocrine-dependent organs: prostate cancer, hypernephroma and testicular tumors. Endocrine therapy is not used in testicular cancer, its value in renal cell carcinoma is limited, whereas it is a dominant form of therapy for prostate cancer. There seems to be a definite relation between androgen receptor content in primary prostatic carcinoma and response to hormonal manipulations. The presence of estrogen receptors is not well documented and probably the major effect of estrogen therapy is indirect, being exerted via the hypothalamo-pituitary axis. Progestin receptors are present in hyperplastic prostate as well as in prostate cancer and may indicate cases sensitive to progestin therapy. The assay method still needs considerable refinement before it can be introduced into clinical practice.
 ...
PMID:Steroid receptors in urological malignancies. 694 77

To assess whether pre-treatment prostatic androgen receptor measurements would be of value in predicting the response to hormonal therapy in patients with prostatic cancer 23 men with metastatic carcinoma of the prostate underwent prostatic biopsy before treatment. Cytosolic and nuclear prostatic androgen receptor contents were measured by a single saturating dose, dextran-charcoal assay. All patients had measurable levels of androgen receptor in prostatic tissue and all demonstrated objective evidence of improvement following hormonal therapy. Thus, if androgen receptor measurements are to be useful in predicting prognosis correlations between quantitative levels of receptor and quantitative aspects of response must be established. In our study response was quantitated by measuring the duration of response and survival following hormonal treatment. The strong correlation between duration of response and survival (p less than 0.01) demonstrated herein suggests that survival in these patients is related directly to the duration of time patients respond to hormonal therapy. Neither total cellular nor cytosolic androgen receptor content correlated with response. However, nuclear androgen receptor content correlated with the duration of response and survival following hormonal treatment (p less than 0.05). Furthermore, in patients with nuclear receptor levels less than 110 fmol. per mg. deoxyribonucleic acid the duration of response (7.1 plus or minus 3.8 months) and survival (14.4 plus or minus 5.9 months) was significantly shorter than in patients with higher levels of nuclear receptor (17.3 plus or minus 10.4 and 24.7 plus or minus 8.8 months, respectively) (p less than 0.05). These findings, which are the first report of a correlation between nuclear androgen receptor content and hormonal responsiveness, suggest that measurements of nuclear receptor may aid in identifying those patients unlikely to obtain a prolonged response from hormonal therapy.
 ...
PMID:Correlation of prostatic nuclear androgen receptor content with duration of response and survival following hormonal therapy in advanced prostatic cancer. 706 20

Using the sucrose density gradient technique, we have compared androgen receptor values obtained in the presence and absence of sodium molybdate from cytosols of surgically obtained human prostate cancer tissue. In all nine prostates examined, inclusion of molybdate in the buffers resulted in an increase in the amount of androgen receptor detected, in some cases dramatically. Since accurate androgen receptor assays could be valuable for therapeutic decision making in prostate cancer, we advocate the inclusion of sodium molybdate in assay buffers to guard against the possibility of false negative or artificially low values.
 ...
PMID:Molybdate and the measurements of androgen receptors in prostate cancer. 725 22

The androgen receptor (AR) is a ligand-dependent DNA transcription factor that binds androgens which cause masculinisation of the developing male fetus. Classical abnormalities of receptor function result in the syndrome of androgen resistance, with resultant failure of normal male differentiation. In more recent years, however, mutations in the AR gene have been described in a number of diverse clinical conditions, from male infertility to prostate and breast cancer through to a form of motor neurone disease (Kennedy's disease). This review discusses the various AR gene mutations found in androgen insensitivity syndrome (AIS) and the other conditions described above, and relates how different mutations, or disruption of different functional domains, contributes to the various phenotypes. Mutations that cause complete AIS usually disrupt the DNA or steroid binding ability of the receptor. In partial AIS, mutations generally decrease receptor affinity for ligand, affect thermostability of the protein, or affect the ability of the receptor to activate transcription of responsive genes. Isolated mutations occur in the steroid binding domain of the receptor in prostate cancer, and many cancers have an identical mutation. Similarly, in the two cases of male breast cancer in which AR gene mutations have been described, the mutations in the DNA binding domain of the receptor are alike. In Kennedy's disease a trinucleotide repeat expansion occurs in exon A of the AR gene, which appears to affect ability of the receptor to bind ligand and activate transcription, although the mechanism of neuronal degeneration remains unknown.
 ...
PMID:Defects of androgen receptor function: from sex reversal to motor neurone disease. 748 16

Microsatellites are highly polymorphic, short-tandem repeat sequences dispersed throughout the genome. Instability of these repeat sequences at multiple genetic loci may result from mismatch repair errors, and occurs in hereditary nonpolyposis colorectal carcinoma and certain sporadic cancers. To examine microsatellite instability during the pathogenesis of human prostate cancer, we screened 48 prostate cancer cases (20 stage B, 10 stage C and 18 endocrine therapy-resistant cancer-death cases) for replication error at 17 microsatellite marker loci on 9 chromosomes. Microsatellite instabilities were found in 7 of 48 cases (14.6%), and all 7 cases showing the instability were poorly differentiated adenocarcinomas. Moreover, microsatellite instabilities were more frequently observed in cancer-death cases (6/18, 33%) than in stage B + C cases (1/30, 3.3%). These data suggest that microsatellite instability is an important genetic change related to the progression of a subset of human prostate cancer cases. It is suggested to be associated with extensive, concurrent molecular changes including androgen receptor gene mutations, as well as frequent loss of heterozygosity at chromosomal regions 8p, 10q, and 16q.
 ...
PMID:Microsatellite instability and other molecular abnormalities in human prostate cancer. 749 15

The molecular mechanisms and genetic changes that lead to the progression of prostate cancer during endocrine therapy are poorly characterized. Here, paired specimens from both untreated primary tumors and from local recurrences were collected from 10 prostate cancer patients treated by conventional androgen deprivation therapy. The genetic progression of the tumors was studied by using interphase fluorescence in situ hybridization and chromosome-specific probes. Six primary tumors (60%) and all ten recurrent tumors were aneuploid by fluorescence in situ hybridization. The recurrent tumors also showed a high degree of chromosome copy number variability from one cell to another. Increased copy number of chromosome X was particularly common in the recurrent tumors. In addition, specific high level amplification of the androgen receptor (AR) gene (Xq12) was detected in three highly aneuploid recurrent tumors. Our findings suggest that hormone-refractory prostate cancers are genetically very complex and show intratumor genetic heterogeneity. Increased copy number of chromosome X and the amplification of the androgen receptor (AR) gene may confer proliferative advantage during androgen deprivation and thus contribute to the development of recurrence.
 ...
PMID:Analysis of genetic changes underlying local recurrence of prostate carcinoma during androgen deprivation therapy. 749 86


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