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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor regression is sometimes observed during glucocorticoid treatment of patients with breast cancer. The possibility of a direct tumor-growth-suppressing effect, mediated by steroid-hormone receptors, cannot be excluded. A 3H-dexamethasone-binding component in the cytoplasmatic fraction of human breast cancers was studied by agar-gel electrophoresis. Of 90 samples, 51% contained a significant amount of an apparent glucocorticoid receptor. In two specimens from metastases, in which a preexisting lymph node structure was almost completely replaced by tumor tissue, the glucocorticoid receptor character of the binding component was studied extensively. The component satisfied the steroid-hormone receptor criteria in being a high affinity (Kd approximately 4--9 X 10(9) M), low capacity binder. Competition studies with excess unlabelled steroids of different classes confirmed the specific glucocorticoid receptor character of the component. Both tumors contained also estrogen and androgen receptors and one contained an apparent progestin receptor.
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PMID:Demonstration of glucocorticoid receptors in human mammary carcinomas. 90 52

Glucocorticoid cytosolic receptors (GR) have been studied in both a primary and in a lung selected (metastatic) series of a B16BL6 murine melanoma. In the primary series tumour there was an initial increase in GR content from 40 to 95.6 fM mg-1 protein. GR levels then fell over the next 11 transplant generations to 10 fM mg-1 protein. In the metastatic series, in the course of six transplant generations, GR content of 73 fM mg-1 protein fell to below detectable levels, i.e. less than 5 fM mg-1 protein. Both the metastatic and primary series tumours showed a significant decrease in doubling times with increasing transplant generation. We therefore suggest that in the primary series tumours, after an initial phase of adaptation from tissue culture to in vivo conditions, the increased growth of the tumours is independent of the loss of hormonal control caused by a reduction in the glucocorticoid receptor content associated with serial transplantation. In the metastatically selected series of tumours, there appears to be a selective growth pressure brought about by the cyclic transplantation procedure which was also accompanied by an increase in metastatic ability.
Clin Exp Metastasis
PMID:Loss of glucocorticoid receptors in B16BL6 murine melanoma associated with serial transplantation, metastatic selection and altered growth properties. 366 22

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

The levels of estrogen, progesterone, androgen and glucocorticoid receptors were assayed in 70 malignant epithelial tumors of human ovaries. The percentage of progesterone, androgen and glucocorticoid receptor-positive tumors was significantly higher in reproductive patients than in menopausal ones. Well-differentiated serous cystadenocarcinomas showed a higher level of progesterone receptors than those characterized by poor differentiation of cells. It was found that steroid hormone receptor profile of primary tumor may be determined in its metastases into the greater omentum whenever tumor cannot be removed. In cases of preoperative chemotherapy, the percentage of receptor-positive ovarian tumors was lower.
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PMID:[Cytoplasmatic receptors of steroid hormones in malignant epithelial ovarian tumors]. 651 72

Measurement of estrogen receptor content in human breast cancer has become a valuable tool to predict the response of a tumor to endocrine manipulations. The aim of this study was to see whether steroid receptor assay could also be used to predict the value of endocrine therapy in human prostatic carcinoma. Biopsies from 25 primary tumors were analyzed with regard to quantity of methyltrienolone (a synthetic androgen) binding to the receptor 20 specimens were receptor-positive and 5 were receptor-negative. The correlation between receptor content and response to endocrine treatment was approximately approximately equal to 80%. The steroid receptor profiles of 5 lymph node metastases were also analyzed. 4/5 contained methyltrienolone receptors and 2/5 contained progestin receptors. 3/5 were glucocorticoid receptor-positive while all specimens were estrogen receptor-negative.
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PMID:Prediction of tumor response to endocrine therapy in prostatic carcinoma based on steroid receptor assay. 693 41

The glucocorticoid receptors were measured and characterized in the transplantable B16 murine melanoma using [3H]-dexamethasone by a charcoal adsorption technique. In the tumor cytosols assayed, the levels of receptors ranged from 44 to 200 fmol/mg protein, and the corresponding Kd's ranged from 2 to 43 nM. Sucrose density gradient analysis showed a peak sedimenting at 7.1S under low-ionic-strength buffer which was completely eliminated with a 100-fold molar excess of unlabeled triamcinolone acetonide in the incubation mixture. This peak of bound radioactivity shifted to the 4.4S region under high-ionic-strength buffer (0.4 M KCl) conditions. Competition experiments, using [3H]dexamethasone and various unlabeled steroids at a 100-fold molar excess, showed characteristics typical of glucocorticoid receptors seen in other tissues. Administration of various glucocorticoids, e.g., dexamethasone, hydrocortisone acetate, and prednisolone, in different doses and regimens showed a marked and significant inhibition of tumor growth as measured by mean tumor diameter and weight. Although glucocorticoid treatment does not seem to affect the incidence of pulmonary metastases, the number of pulmonary nodules appears to be significantly greater in some groups treated with higher doses of these drugs. In survival experiments, administration of hydrocortisone acetate in various doses and regimens also resulted in a significant increase in the median survival of mice compared to 0.9% NaCl solution-treated controls. These results indicate that the growth inhibition of B16 melanoma by glucocorticoids may be a direct effect mediated by interaction with the glucocorticoid receptor.
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PMID:Glucocorticoid receptors and the effect of glucocorticoids on the growth of B16 melanoma. 721 39

We analysed the glucocorticoid receptor (GR) function and its ability to modulate cell-cell interactions between the PA-III rat prostate cancer and UMR 106 osteoblast-like rat osteosarcoma cells as an in vitro model for studying GR function in PA-III cell-induced tumor and blastic reaction in rat bone. Intact GR was detected by ligand binding assays, DNA band-shift, and GR trans-activation analysis of PA-III and UMR 106 cells transiently transfected with the mouse mammary tumor virus thymidine kinase-chloramphenicol acetyltransferase reporter gene. Dexamethasone and transforming growth factor beta 1 (TGFbeta1) inhibited the growth of PA-III and UMR 106 cells. Dexamethasone's inhibition of PA-III and UMR 106 cells was reversed by anti-TGFbeta1 antibody and exogenous insulin-like growth factor I (IGF-I). Exogenous IGF-I, urokinase-type plasminogen activator (uPA), UMR 106 conditioned media (CM) and PA-III CM stimulated the proliferation of PA-III and UMR 106 cells. The mitogenic activity exerted by uPA and PA-III CM in UMR 106 cells was completely neutralized by anti-IGF-I specific antibody. In addition, dexamethasone up-regulated TGFbeta1 mRNA and down-regulated uPA mRNA expression in PA-III cells without affecting TGFbeta1 and uPA mRNA expression in UMR 106 cells. These data suggested that TGFbeta1, uPA, and IGF-I mediate at least in part cell-cell interactions and GR function in PA-III prostate cancer and UMR 106 osteosarcoma cells.
Clin Exp Metastasis 1997 May
PMID:Glucocorticoid receptor function possibly modulates cell-cell interactions in osteoblastic metastases on rat skeleton. 917 22

We investigated the ability of important regulators of osteoblast function, such as insulin-like growth factor I (IGF-I), transforming growth factor beta 1 (TGF beta 1), and urokinase-type plasminogen activator (uPA) to act as mediators in cell-cell interactions between osteoblast-like cells and metastatic prostate cancer cells, in vitro. In addition, we assessed whether these growth substances can (a) mediate glucocorticoid receptor (GR) function and (b) be implicated in dexamethasone-induced regression of osteoblastic tumors. Exogenous IGF-I, rat/human uPA, and PA-III (rat)/PC-3 (human) prostate cancer cells conditioned media (CM) stimulated the proliferation of rat (UMR 106 cells) and human (MG-63 cells) osteosarcoma cells. This mitogenic activity was completely neutralized by anti-IGF-I specific antibody. In addition, dexamethasone decreased cell growth, up regulated TGF beta 1 mRNA, and down regulated uPA mRNA expression in prostate cancer cells. Furthermore, it inhibited cell growth by activating latent-TGF beta 1 in osteoblast-like cells. In addition, dexamethasone down regulated the expression of IGF-I mRNA in osteoblast-like cells. Therefore, it is conceivable that uPA, TGF beta 1 and IGF-I mediate at least in part cell-cell interactions and GR function in osteoblastic metastases. Conceivably, regression of the osteoblastic tumors produced by high-dose dexamethasone treatment in hormone-refractory prostate cancer patients is been mediated by differential regulation of growth factors, locally.
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PMID:Growth factors mediate glucocorticoid receptor function and dexamethasone-induced regression of osteoblastic lesions in hormone refractory prostate cancer. 917 84

To understand the relationship between pituitary adenoma and carcinoma, four adrenocorticotropic hormone-producing pituitary adenomas and corresponding metastatic carcinomas were studied. All were functional macroadenomas (three cases of Nelson syndrome and one of Cushing disease) that initially invaded the sella turcica and occurred in women ranging in age from 17 to 66 years (mean 45 years). Metastases (two craniospinal and two systemic) occurred after latency periods of 6 to 13 years. Histological specimens were immunostained for pituitary hormones, Ki-67 antigen (MIB-1), p53 and p27 proteins, D-type cyclins, and glucocorticoid receptor messenger (m)RNA. The DNA content of the specimens was assessed using Feulgen stain. Reactivities were quantified by digital image analysis. Primary/recurrent lesions and metastatic tumors differed according to their respective mean mitotic indices (1.2/10 hpf compared with 4.3/10 hpf), MIB-1 labeling (1.7% compared with 8%), p53 staining (37.3% compared with 49.9%), and p27 labeling (48% compared with 25%). Cyclin D, immunoreactivity provided no prognostically significant information. Glucocorticoid receptor mRNA was detected in all cases. Results of a ploidy analysis were variable and nonprognostic. In keeping with the 2000 World Health Organization classification of endocrine neoplasms, our findings support the concept that primary tumors that exhibit mitotic activity, an increased (> 3%) MIB-1 labeling index, and/or p53 immunoreactivity should be termed "atypical adenomas" to denote their aggressive potential and the possibility of future malignant transformation.
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PMID:Corticotroph carcinoma of the pituitary: a clinicopathological study. Report of four cases. 1183 11

The aggressive behavior of breast cancer cells can at times be modulated by hormonal mechanisms. Exposure to glucocorticoids (GC) has been shown to stimulate the invasiveness, motility and adhesiveness of breast cancer cells containing the glucocorticoid receptor. This is largely explained by GC-associated overexpression of the c-fms proto-oncogene, which encodes the receptor for the colony stimulating factor-1 (CSF-1). Our objective is to investigate additional GC-associated genetic alterations that could modulate c-fms related malignant behavior in breast cancer cells. A microarray technique using an oligonucleotide array representing 16,700 known expressed human genes was used to analyze the gene expression profile of breast cancer cells exposed to dexamethasone (Dex) or vehicle. Results were confirmed by western blot analysis. Six genes were found to be consistently differentially overexpressed in the Dex-exposed cells compared to control. We focused on serum-glucose kinase 1 (SGK1), a serine-threonine kinase known to be involved in intracellular signal transduction pathways and induced by GC and serum. An adhesion assay was performed on extracellular matrix after exposing the breast cancer cells to Dex, CSF-1 or to Dex or CSF-1 plus LY294002, a functional inhibitor of SGK1 action. Exposure to LY294002 significantly decreased both CSF-1 and Dex-induced adhesiveness to the level of control cells. SGK1 may act as a downstream intracellular regulator of c-fms, particularly of c-fms-induced adhesiveness of breast cancer cells after exposure to GC or CSF-1. This finding may have implications for potential therapeutic interventions aimed at decreasing the aggressiveness of breast cancer cells.
Clin Exp Metastasis 2004
PMID:SGK1, a potential regulator of c-fms related breast cancer aggressiveness. 1567 45


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