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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The transplantable human prostatic adenocarcinoma, PC-82, has been shown to be a suitable model for the study of several aspects of androgen-regulated tumor growth. This tumor contains an androgen receptor, and the purpose of the present investigation was to characterize this androgen receptor with respect to hormone specificity, sedimentation coefficient, dissociation constant, Stokes radius, ionic properties, and molecular mass. Cytosol was prepared from tumor tissues grown in athymic nude mice, which were castrated 10 days before harvesting the tumor. Scatchard plot analysis revealed a binding protein with a Kd of 0.1 nM for R1881 (methyltrienolone) and binding capacity of 120 fmol/mg protein. The receptor showed a high affinity for R1881, testosterone, and 5 alpha-dihydrotestosterone, respectively, whereas no or little affinity was found for progesterone and estradiol. In the presence of 10 mM molybdate the androgen receptor in PC-82 cytosol eluted from an FPLC anion exchange column (Mono Q) at 0.32 M NaCl, which is identical to what has been found for androgen receptors from rat prostate and calf uterine cytosol. Photoaffinity labeling of the [3H]R1881-androgen receptor complex and subsequent analysis on SDS-polyacrylamide gels resulted in a covalently labeled protein with a molecular mass of approximately 50 kD. The androgen receptor of the PC-82 tumor had a sedimentation coefficient of 4S and a Stokes radius of 3.3 nm at high ionic strength (0.4 M NaCl). It is concluded that the PC-82 tumor contains a binding protein with the properties described for androgen receptors present in prostate tissue.
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PMID:Characterization of androgen receptors in a transplantable human prostatic adenocarcinoma (PC-82). 295 63

The nuclear androgen receptor (ARn) content of cancerous prostatic tissue has been investigated as a prognosticator for time to progression under endocrine therapy. In 1981 a prospective study was started to investigate whether the ARn content in biopsy specimens of patients with prostatic carcinoma predicts the duration of response following hormonal treatment. ARn was estimated by a microassay which involves extraction of nuclear pellets with a heparin-containing buffer, exchange labeling of the nuclear extract with 3H-R1881, and quantitation of the receptor with protamine sulphate precipitation. One hundred and fifteen patients with prostatic cancer entered this study; 47 patients had evidence of metastatic disease as proven by bone scan. Forty-two patients were treated by orchiectomy; 37 of these patients are evaluable with a minimal follow-up of 30 months. A relationship between the nuclear androgen receptor content and the time to progression following orchiectomy in these patients with metastatic disease of the prostate was not found. This could possibly be attributed to the heterogeneous nature of the prostatic tumor tissue with respect to the distribution of the ARn. We conclude that androgen receptor assay in needle biopsies, at least in this study, had no value for the prediction of the time to progression after orchiectomy.
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PMID:Prediction of time to progression after orchiectomy by the nuclear androgen receptor content from multiple biopsy specimens in patients with advanced prostate cancer. 337 41

Endocrine therapy, which consists of orchiectomy followed by administration of large doses of estrogen, then a reduced amount of estrogen, has been applied as the main treatment for stage D2 prostatic cancer. Alternatively, anti-androgen is used for elderly patients or those with cardiovascular disorders. Survival rate with endocrine therapy at 5 and 10 years was 35% and 16%, respectively. Therefore, in Japan, a better survival is shown than that reported in western countries using much smaller doses of estrogen. Most of the side effects caused by estrogen are not serious. Side effects caused by anti-androgen are few except for loss of libido. At the start of treatment, more than 80% of patients showed a response, but gradually relapse occurred and only 20% were well controlled 5 years after the start. Factors influencing the survival were pathological grade, response to endocrine therapy judged by the level of prostatic acid phosphatase 4 weeks after the start, and R1881 (methyltrienolone)-binding protein observed histochemically. The latter protein was also correlated with the grade and response to endocrine therapy. Relapse after endocrine therapy might be attributable to adaptation or mutation progressing to androgen-independent cells. Using SC 115, an androgen-dependent mouse tumor, these two types of relapse were demonstrated. Gradual progression to undifferentiated cancer was noticed between pretreatment biopsy and autopsy. Relapse in human prostatic cancer may thus be partly due to genetic change to a resistant clone.
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PMID:[Prostatic carcinoma. I: Androgen dependency of prostatic carcinoma]. 338 34

There are many data that suggest that the larynx is a target organ for steroid hormones, especially androgens. Since laryngeal cancers occur much more often in males, it is conceivable that androgens might be the growth-stimulating factor for such tumors. In order to test this concept further, neoplastic tissues from 68 patients (64 males, 4 females) were obtained during planned total laryngectomies and were tested for the presence of androgen (AR) and estrogen (ER) receptors. In 18 cases progesterone receptors (PgR) were also quantified. The dextran-coated charcoal technique was used to determine hormone receptors and the number of the binding sites and the equilibrium constant of dissociation were calculated according to Scatchard. 3H-R1881 was used as the ligand for the measurement of AR, 3H-estradiol for ER, and 3H-R5020 for PgR. AR was present in 11 tumor specimens (1 female, 10 males) and the concentration varied from 2.8 to 17.1 fmol/mg proteins. ER were found in 6 tumors (1 female, 5 males) in concentrations of 2.9-11.2 fmol/mg proteins. Three tumor specimens contained both AR and ER. All tumors analyzed lacked PgR. These results suggest that at least some laryngeal carcinomas might be hormone dependent, indicating that certain patients could benefit from antiandrogen therapy.
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PMID:Cytoplasmic steroid receptors in cancer of the larynx. 339 69

For basic studies of receptor dynamics in androgen-responsive tissues and cells, the autoradiographic and cytochemical procedures were applied to cultured tumor cells (DU-145 and PC-3). Uptake and retention of 3H-R1881, a potent synthetic androgen, were observed in DU-145 cells. The radioactive labelling was intense, and solely confined to the nuclei of DU-145 cells. Radioactivity over PC-3 cells was minimal. For assessing binding specificity, DU-145 cells were incubated with 3H-R1881 in the presence or absence of either unlabelled R1881, testosterone, progesterone, estradiol-17 beta, or corticosterone. The displacement of 3H-R1881 with R1881 and testosterone was significant, while no displacement was observed with other steroids. Nuclear localization of cytochemical staining of the dihydrotestosterone-peroxidase conjugate was evident in DU-145 cells. Our results indicate that androgen receptor may reside primarily in target cell nuclei of androgen-responsive tissues and tumors.
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PMID:Autoradiographic and cytochemical localization of androgen in human prostatic cancer cell lines. 348 7

Clinical and experimental evidence suggests a role for estrogen in the natural history of desmoid tumors (DT). Antiestrogen (tamoxifen) has been used empirically in some patients with significant tumor regression. To further investigate the mechanism of hormonal influence on desmoid tumors we initially characterized the cytosol estrogen receptor (ER) and antiestrogen binding sites (AEBS) in microsomal fractions of 15 cases of DT. Biopsy specimens were obtained from nine female and six male patients. ER assay was determined in cytosol (105,000 g) and the AEBS was detected in the microsomal fraction (7000 g for 20 min) by a DCC assay technique. ER was present in 33% of DT assayed (5/15), with equal incidence in males and females. Receptor content in female patients was higher than in male patients (26.52 +/- 16 vs 10.82 +/- 8.32 fmol/mg protein). Dissociation constant (Kd) range (0.44-3.97 nM) was well within the values seen in other estrogen target tissues. The AEBS were detected in 79% of the cases. The mean binding value was 236.7 +/- 170.2 fmol/mg protein. Kd values were between 0.39 and 5.97 nM. ER settled predominantly in the 4S region and AEBS settled in the 5-5.5S region in a 5-20% sucrose gradient. AEBS was detected in seven patients with negative ER. No correlation between ER and AEBS contents was observed. Competition studies revealed minimal binding with either DEX, DHT, R5020, and R1881, but partial binding with tamoxifen in cytosol and estradiol in microsomal fractions. ER and AEBS assays may be of prognostic significance in the natural history of these tumors.
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PMID:Estrogen and antiestrogen binding sites in desmoid tumors. 377 30

The ductus deferens smooth muscle tumor cell line (DDT1MF-2) contains receptors for, and is stimulated by, androgens. Cells cultured in the absence of androgens maintain a basal level of androgen receptors. Following incubation with various concentrations of the synthetic androgen methyltrienolone (R1881) for 1-6 h, the concentration of these receptors increased from 6.0 to 12.2 fmol/micrograms of DNA, while the equilibrium dissociation constant (Kd) of 0.5 nM for this steroid remained unchanged. The steroid-induced increase in androgen receptor levels was specific for androgens and dependent upon protein synthesis. The mechanism of receptor augmentation was examined by utilization of isotopically dense amino acids to determine rates of receptor appearance and degradation in the presence or absence of [3H]R1881. In the absence of androgens, the half-life of the androgen receptor was 3.1 h, with a rate constant (kD) of 0.22/h. In the presence of 1 nM [3H]R1881, however, the half-life was 6.6 h, with kD = 0.11/h. The rate constant for receptor synthesis (ks) in the absence or presence of [3H]R1881 was calculated to be 1.35 and 2.23 fmol/micrograms of DNA/h, respectively. Thus, androgen-induced androgen-receptor augmentation is explained by an increase both in receptor half-life and in rates of receptor synthesis.
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PMID:Mechanism of androgen-receptor augmentation. Analysis of receptor synthesis and degradation by the density-shift technique. 387 Nov 97

Primary endometrial carcinomas from 35 non-treated patients were investigated by measurement of androgen receptors in the tumor cytosols. Receptor analysis was done with a labelled synthetic androgen, methyltrienolone 3H-R1881 and triamcinolone acetonide, and dextran-coated charcoal absorption. The concentrations of androgen receptors in the endometrial carcinomas were, in decreasing order: highly-differentiated tumors, 15.7 +/- 1.8 (fmol/mg protein, mean +/- SE) (number of cases, 21); moderately differentiated tumors, 4.6 +/- 1.6 (n = 7); poorly differentiated tumors, undetectable in 7 out of 8 cases. Highly-differentiated tumors contained a much greater concentration of receptors than the two less differentiated ones. One highly-differentiated endometrial carcinoma with pyometra virtually lacked the receptor. The moderately differentiated endometrial carcinomas contained very low levels of the receptors. The poorly differentiated tumors virtually lacked the receptors. Metastatic lymph nodes from primary endometrial carcinomas with moderate differentiation had a very low receptor level. From these results, it is concluded that human endometrial carcinomas, particularly with histologically high differentiation, contain a considerable amount of androgen receptor and that the receptor concentrations appear to correlate with the histologic grade of tumor differentiation.
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PMID:Correlation of androgen receptors with histological differentiation in human endometrial carcinomas. 387 14

This paper describes the dose-response inhibitory effects of a synthetic androgen, methyltrienolone, on the growth of a grade II endometrial adenocarcinoma in vitro. Derived from a nude mouse heterotransplant, this cell line has maintained the morphological characteristics of the original human tumor, remains tumorigenic in the nude mouse, forms colonies on soft agar, and exhibits low levels of estrogen receptors. Data reported in this paper indicate that the cells contain androgen binding sites. At low doses of 0.25 micrograms/ml methyltrienolone had no effect on these cells, whereas at 1.0 and 10.0 micrograms/ml there was significant dose dependent inhibition of cell growth and an increase in the cell doubling time. Both testosterone and dihydrotestosterone were not inhibitory to the cells except at high doses where inhibition was slight. Methyltrienolone was not inhibitory to normal human foreskin fibroblast cultures tested as a control for cytotoxicity of the synthetic androgen. These data suggest that androgens may play a role in the treatment of tumors not responsive to conventional forms of hormonal therapy.
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PMID:Inhibition of endometrial carcinoma cell cultures by a synthetic androgen. 387 66

No difference was found in the values of the equal constants of dissociation and the number of sites specifically binding [3H] DHT and [3H] R1881 in the cytosols of tumor cells and human prostatic nodular hyperplasia. The above data suggest that in the determination of cytoplasmic androgen receptors in healthy and tumorous tissues of the target organs one can use both natural (DHT) and synthetic (R1881) steroids precipitating the hormone-receptor complex with protamin sulphate.
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PMID:[Comparison of natural and synthetic ligands for determining androgen receptors in prostatic tumors and prostatic nodular hyperplasia]. 619 90


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