Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Steroid hormone receptors have been evaluated as independent prognostic factors as well as predictive factors for endocrine manipulation in the clinical management of breast cancer. The contribution of each receptor or combinations of different receptors remains controversial. In cytosols from 224 patients with operable breast cancer (stages I & II), estrogen receptor (ER), progesterone receptor (PgR) and androgen receptor (AR) content have been measured. An improved AR-assay has been used in order to circumvent some of the problems inherent in other methods. In this study, 91.1% of the patients were classified as AR 'positive' (i.e. greater than or equal to 10 pmol/g). The steroid hormone receptors were significantly correlated (P less than 0.001). Taking the median value of AR as cut-off (50.5 pmol/g), a significantly higher incidence (P = 0.004) of node negative patients was found in the group with a lower AR content. In a multivariate analysis the AR category (median value used as cut-off) was shown to be an independent predictor of the likelihood of axillary metastases (P = 0.001). AR category, however, did not reveal any significant prognostic information concerning relapse free survival. A subpopulation of node positive patients with ER positive tumors, have been included in a randomized trial on the role of tamoxifen as an adjuvant treatment compared with no endocrine treatment. In a multivariate analysis, PgR status was shown to be a single independent prognostic factor (P = 0.016) for relapse free survival in patients with a lower AR content (less than median value). The improved AR assay used in the present study may provide a basis for more correct estimation of the AR content in an individual tumor. The present study suggests that AR analysis and the use of a well-chosen cut-off level may add information about tumor biology to increase our understanding of breast cancer biology and treatment.
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PMID:Androgen receptors in operable breast cancer: relation to other steroid hormone receptors, correlations to prognostic factors and predictive value for effect of adjuvant tamoxifen treatment. 158 3

The capacity of steroidal regulatory influence on benign and malignant mammary tissue in cats was investigated. Estrogen, progestin, and (in some cats) androgen receptor levels in the cytosol were measured by a multiconcentration dextran-coated charcoal method in non-affected mammary tissue (NAMT) and in benign and malignant mammary lesions from 34 cats. Receptor levels less than 5 fmol/mg protein were considered negative. Since 3 out of 4 NAMT samples had low-positive estrogen receptor and progestin receptor levels, we considered specimens in which tumour cells were intermeshed with NAMT separate from "pure" tumour specimens. The variation in estrogen receptor expression between the different tissues was moderate, there being 9/17 malignant lesions (without NAMT) estrogen receptor+ as compared with 6/6 benign lesions (without NAMT) (p less than 0.05). The variation in progestin receptor expression was greater (p less than 0.02), with only 5/17 malignant lesions-(without NAMT) progestin receptor+ as compared with 6/6 benign lesions (without NAMT). The difference in progestin receptor levels between these 2 groups was also statistically significant. In 5 cats metastases were also assayed and 2 had a low-positive estrogen receptor level, whereas 1 had a low-positive progestin receptor level. Two of 9 malignant lesions (without NAMT) had positive androgen receptor levels. Comparison of the steroid receptor expression of human and feline mammary cancer indicates that estrogen receptor and progestin receptor levels are lower in the latter. This may indicate that loss of steroid hormone dependency occurs at an earlier stage of the disease in feline mammary cancer than in human breast cancer.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Steroid receptors in mammary tumours of the cat. 180 1

The steroid receptor profile in seven prostate cancer metastases was compared with the profile in seven primary prostate cancers. The secondaries were all lymph node metastases, obtained during pelvic lymphadenectomy, preceding radical prostatectomy or irradiation. Cytosol androgen receptor content was higher in metastases, whereas the nuclear androgen receptor content was only one-fourth that in primary cancer. Cytosol progesterone as well as estrogen receptor contents were markedly lower in metastases compared with primary cancer. The steroid receptor profile differed very little between primary cancer and normal tissue. Primary prostatic carcinoma is usually obtained at early stages of the disease, whereas metastases represent a dedifferentiated, more aggressive cell population. This may explain the low amounts of progesterone, estrogen, and nuclear androgen receptor levels. The total androgen receptor content was similar in metastatic and primary disease, however, with a shift towards a cytosolic predominance in metastases. Possibly androgen receptors in metastatic disease are "deactivated."
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PMID:Steroid receptor profile in human prostate cancer metastases as compared with primary prostatic carcinoma. 200 20

Serum melatonin was determined over 24 hours in 35 patients with breast cancer with either a fresh primary tumor (n = 23) or a secondary tumor (n = 12) and in 28 patients with untreated benign breast disease (controls) having a fibroadenoma (n = 10), fibrocystic mastopathy (n = 14), or other breast diseases (n = 4). Circadian rhythms existed in all groups with acrophases at 2 a.m. A 50% depression of peak and amplitude occurred in the group of patients with primary breast cancer compared with age-matched controls (P less than 0.001, P less than 0.01). The peak declined with increasing tumor size: 27% at Stage T1, 53% at T2 (P less than 0.001), and 73% at T3 (P less than 0.05). In contrast, patients with secondary breast cancer, particularly those receiving antiestrogen therapy, had a melatonin peak similar to controls. These results demonstrated a transient depression of pineal melatonin secretion in primary breast cancer and indicated a dynamic role of the pineal gland in malignancy. To investigate some endocrine effects of a depressed melatonin peak, the 24-hour rhythms of prolactin (PRL) and thyroid stimulating hormone (TSH) were determined in patients with primary breast cancer and compared with patients with secondary breast cancer. The PRL had significant circadian rhythms in both groups; but acrophases occurred at midnight in patients with secondary breast cancer, and there were unusually high concentrations at noon in patients with primary breast cancer. Circadian rhythms were not seen for TSH, but the 24-hour average secretion was depressed by 45% (P less than 0.01) in patients with primary breast cancer. The abnormal concentrations of PRL and TSH in these patients could be due to a depressed melatonin peak normally serving as a central circadian synchronizer and modulator of the secretion of adenohypophysial hormones. Additionally, a positive correlation existed between the nocturnal melatonin peak and progesterone and androgen receptor concentrations in primary tumors indicating a direct involvement of melatonin in the growth control of breast cancer.
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PMID:Stage-dependent depression of melatonin in patients with primary breast cancer. Correlation with prolactin, thyroid stimulating hormone, and steroid receptors. 273 89

Activities of several steroid metabolizing enzymes (steroid sulfate-sulfatase, 17 beta-hydroxysteroid dehydrogenase, 5 alpha-reductase, and 3 alpha beta-hydroxysteroid dehydrogenase) as well as total tissue content and subcellular distribution (nuclear-extranuclear) of several androgen precursors, active androgens, and androgen deactivation products (DHEA sulfate, DHEA, 5-androstenediol, 4-androstenedione, testosterone, DHT, and 3 alpha-androstanediol) were quantified in primary tumors and lymph node metastases of human prostatic cancer obtained from patients without previous endocrine manipulation. Primary tumors were compared to benign parts of the same prostates, and the metastases were compared to their primary tumors. All enzymes and steroids found in benign prostatic tissues could also be detected in the malignant tissues. Even the capacity to accumulate active androgens in the nuclei was found to be unchanged in nearly all of the samples. Lower activities of hormone-dependent enzymes were observed in the cancers, suggesting a less efficient utilization of hormonal stimuli. Most striking changes found in the malignant tissues were a subtotal loss of 5 alpha-reductase activity and a metabolic shift to testosterone, which was more pronounced in samples from metastatic disease as compared to samples from non-metastatic disease. In conclusion, primary tumors and metastases of prostatic cancers not treated by endocrine manipulations retain their androgen receptor system and possess the same capacity to metabolize adrenal androgen precursors along the pathway to DHT as benign prostatic tissue. Consequently, they should be able to use at least androstenedione for production of active androgens directly in the target tissue.
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PMID:Androgens, adrenal androgen precursors, and their metabolism in untreated primary tumors and lymph node metastases of human prostatic cancer. 285 35

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

Progestin, estrogen, androgen, glucocorticoid as well as mineralocorticoid receptors (PR, ER, AR, GR and MR, respectively) were all evaluated with specific synthetic radioligands (biochemical assays) in 25 meningiomas, 9 gliomas and 4 brain metastases. In meningiomas the main steroid hormone receptors appeared to be the progestin receptor, present in 24/25 cases (mean level: 7 105 fmol/gT) and the androgen receptor, present in 23/25 cases (mean level: 2 265 fmol/gT). Progestin receptor levels were found to be significantly lower in meningiomas of the fibroblastic subtype whereas none of the steroid hormone receptors were detected in the anaplastic case. On the other hand, glucocorticoid receptor levels were related to the preoperative glucocorticoid therapy. In gliomas only estrogen receptors (2/9 cases) and especially androgen receptors (8/9 cases) were noticeable: the latter seemed to be related to the histological types and to the sex of patients. No receptors were found in any of the four studied metastases, including one from breast cancer. The biochemical characterization of the receptors as well as their relevance to tumor biology and to the physiology of the normal tissues where tumors arise, were discussed, and biochemical data were compared with those previously reported.
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PMID:Steroid hormone receptors in human meningiomas, gliomas and brain metastases. 608 14

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.
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PMID:Androgen receptor assays in advanced prostatic cancer. 637 68

The remission rates after endocrine and cytostatic treatment were determined in 192 female patients with advanced breast cancer depending on the estrogen, progesterone, and androgen receptor content and on the disease-dominant site. Of 60 women with tumors containing estradiol receptors 39 responded to endocrine treatment. This was only true in two of 31 women without estradiol receptors. Tumors which contained binding sites for both estradiol and progesterone had a higher remission rate after endocrine therapy than those with estradiol receptors only. Remission rates after polychemotherapy were also higher in tumors with binding sites for estradiol as well as for progesterone. The localisation of metastases seems to be of lesser importance for the remission rate than the receptor content. Liver metastases are an exception. Here, no remissions could be observed with endocrine treatment even if ER and PR were present. The median remission rate was 9 months for hormonally treated patients and 10 months for those undergoing chemotherapy. The median survival time after chemotherapy is 18 months higher for responders than for non-responders. This difference is 15 months with endocrine treatment. Two years after the start of endocrine treatment 60% of the responders but only 20% of the non-responders were still alive. Based on our results together with histomorphological studies and the evaluation of recurrence and survival it can be assumed that carcinomas, which by nature follow a more benign course, do contain estradiol receptors.
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PMID:Steroid receptors and response to endocrine treatment and chemotherapy of advanced breast cancer. 722 82

Nearly all primary prostatic carcinomas have been found to express the androgen receptor (AR) protein, which is the intracellular mediator of androgen action. To gain a better insight into the mechanisms of androgen independence of advanced prostatic carcinoma, it is important to know whether the AR is also present in metastases of androgen-independent tumors. We have assessed the status of the AR and the prostate-specific antigen in 22 metastases of 18 patients with progressive prostate cancer. In 18 cases, the metastases were localized in bone, in 3 cases in the epidural space, and in 1 case in the periosteum. All but one patient had received some kind of endocrine treatment for prostatic carcinoma. Paraffin-embedded tissue sections were stained for the AR following a streptavidinbiotin-peroxidase protocol with the polyclonal antibody PG-21, which is directed against amino acids 1 through 21 of the rat and the human AR. The percentage of AR-positive cells was evaluated on the basis of an arbitrary 4-point scale. All 22 tumor metastases displayed AR positivity. One AR-positive metastatic lesion did not stain for prostate-specific antigen, but in all other metastases, this protein was detected by means of immunohistochemistry. The present study provides evidence that, unlike androgen-independent prostatic carcinoma cell lines, distant prostatic carcinoma metastases do express the AR. These findings indicate that the AR may be involved in the progression of prostate cancer.
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PMID:Distant metastases from prostatic carcinoma express androgen receptor protein. 754 9


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