Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transcriptionally active nuclear extracts from human breast carcinoma cells (T47D) were used to compare the action of progestins and several antiprogestins of the 11 beta-aryl substituted steroid series on the DNA-binding properties and the trans-activating potential of progesterone receptor (PR) in vitro. Using the gel-shift assay we identified a novel type of antiprogestin (ZK98299, type I), which in contrast to type II antiprogestins, including RU486, does not induce binding of PR to progesterone response elements (PREs). In competition experiments excess of type I antiprogestin inhibits induction of DNA binding of PR by progestins and type II antiprogestins suggesting that its binding to PR interferes with the formation of stable receptor dimers. Moreover, we demonstrate that the antagonistic action of ZK98299 can be fully mimicked in vitro by using cell-free nuclear extracts from T47D cells and a 'simple' test promoter. In contrast, type II antiprogestins known to induce certain promoters in vivo exert strong agonistic effects on in vitro transcription of the test template used.
 ...
PMID:Two types of antiprogestins identified by their differential action in transcriptionally active extracts from T47D cells. 203 Sep 42

We recently reported that a subpopulation of immunoglobulin G (IgG) in man interacts with the hormone-binding site of estrogen receptors (ER), competes with [3H]estradiol (E2) uptake, and decreases effective ER concentrations in cell cultures. The present work further characterizes the immunological properties of these antibodies and defines their biological activity. Using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting techniques, enriched preparations of the natural anti-ER IgG subpopulation (IgGs) were found to specifically immunoprecipitate ER extracted from MCF-7 mammary carcinoma cells and to compete with [3H]tamoxifen-aziridine for ER binding. During 18-h incubations IgGs decreased [3H]E2 binding capacity of MCF-7 cells in a dose-dependent manner similar to E2. Like E2 but unlike antiestrogens, this biological effect corresponded to down-regulation of the receptor protein and depended on a mechanism specifically inhibited by actinomycin D. Moreover, IgGs antagonized the decrease of [3H]E2 binding capacity produced by the strong antiestrogen methyl-hydroxytamoxifen; this antagonism was additive to that of E2. On the other hand, IgGs like estrogens increased progesterone receptor concentrations and cathepsin D secretion. The biological activity of IgGs was neutralized by anti-IgG antibodies and by ICI 164,384, a "pure" steroid antagonist of E2, confirming that immunoglobulins G were responsible for this activity and acted at the E2-binding site. These observations indicate that some natural antibodies in man can function like potent estrogens on ER and mammary cells.
 ...
PMID:Estrogen-like activity of a subpopulation of natural antiestrogen receptor autoantibodies in man. 203 91

The influence of high dietary fat on the malignant intensity and the hormone receptors of 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary carcinoma in female Sprague-Dawley rats were analyzed by the tumor incidence and growth, the DNA histogram type, the DNA index, the S-phase fraction, and the estrogen receptor (ER) and progesterone receptor (PgR) assays. The rats were fed either a low-fat (0.5% corn oil) diet or a high-fat (20% corn oil) diet after the DMBA administration. Tumor incidences in the low-fat and the high-fat diet groups were 46 and 86%, respectively (p less than 0.01). Tumors in the high-fat diet group were also significantly larger than those in the low-fat group. Average tumor latent period was significantly shorter in the high-fat diet group, comparing with that in the low-fat diet group (p less than 0.01). Sixty-nine percent of the tumors in the high-fat diet group had aneuploid type, while only 8% of those in the low-fat diet group had aneuploid type. The DNA index and S-phase fraction also were significantly higher in the high-fat diet group (p less than 0.01). But the ER and PgR contents were not different between both groups. Therefore, these results suggest that a high dietary fat could increase the malignant intensity of the tumor but does not influence the hormonal responsiveness of these tumors.
 ...
PMID:Effects of high dietary fat on the total DNA and receptor contents in rats with 7,12-dimethylbenz[a]anthracene-induced mammary carcinoma. 211 97

In the glands of cyclic endometria, proliferative activity (PA), as revealed by expression of the Ki-67 antigen, is highest in the proliferative phase (P) and early secretory phase (S1). The PA decreases in the middle secretory phase (S2). In the stroma the PA is low during the whole cycle. In P and S1, the oestrogen receptor (ER) and the progesterone receptor (PR) are strongly expressed in glands and stroma. The number of positive cells and the staining intensity decreases in S2, particularly in the glands. In atrophic endometria, fibro-glandular polyps and in endometria with arrested secretion the PA is low in both glands and stroma. ER and PR can be detected in glands and stroma. The PA in atypical hyperplasias is only slightly higher than in cyclic endometria and endometria with simple hyperplasia. The ER and PR levels are comparable to those in proliferative endometria. The PA of endometrial adenocarcinomas is positively and the ER and PR negatively correlated with the degree of de-differentiation. No ER-negative carcinoma displays the PR. Immunohistologically, non-neoplastic receptor positive tissue can be seen in many ER- and PR-negative carcinomas. These structures may falsify the biochemical receptor analysis.
 ...
PMID:Steroid receptors and proliferative activity in non-neoplastic and neoplastic endometria. 211 96

In the present study, chemotherapy with 5-fluorouracil(5-Fu), endocrine therapy with tamoxifen (TAM), and chemoendocrine therapy with concominant use of 5-FU and TAM were performed and compared for DMBA-induced rat mammary carcinoma, a hormone-dependent tumor. The study was designed to assess the usefulness of chemoendorine therapy based on the antitumor effects and changes in hormone receptor levels. The response rates in the groups treated with 5-Fu or TAM alone and the combination of 5-Fu and TAM were 60%, 50% and 62%, respectively. There was no difference in these response rates. The tumor regression rates in these treatment groups were 22 +/- 69%, 20 +/- 54% and 46 +/- 37%; again there was no difference among the three groups. After treatment, the estrogen receptor (ER) and progesterone receptor (PgR) levels decreased significantly in the groups treated with TAM alone and the combination of 5-FU and TAM but remained unchanged in the group treated with 5-FU alone. The decreases in the ER and PgR levels in responsive tumors after treatment were considerably greater in the groups greated with TAM alone and the combination of 5-FU and TAM than in the group treated with 5-FU alone. However, the changes in the receptor levels in nonresponsive tumors did not differ among the three treatment groups. Moreover, there were no differences in the antitumor effects and changes in receptor levels between the groups treated with TAM alone and the combination of 5-FU and TAM. These results suggest that the antitumor effect observed in the combination therapy with 5-FU and TAM was mainly due to the action of TAM. In brief, the expected additive effects of chemoendocrine therapy were not observed.
 ...
PMID:Chemoendocrine therapy in DMBA-induced rat mammary carcinoma. 212 82

The dissatisfying results achieved in the therapy of ovarian carcinoma with an unchanging low rate (between 10% and 30%) of five-year-survival were the reason for efforts to develop a new treatment scheme combining chemotherapy with hormone therapy for epithelial ovarian carcinoma in FIGO stages III and IV. Basic theoretical and experimental reflections: Although in many cases patients may show good response to standard chemotherapy containing cisplatin, a large percentage (70% to 90%) suffers a relapse due to the fact that single tumour cells are resistant to chemotherapy. In order to counteract this resistance we developed a method of therapy (in accordance with the ideas of Coldman and Goldie) based on the sequential application of various non cross-resistant cytostatic agents. This new regimen, comprised of Doxorubicin, Cisplatin, Vincristine, Cyclophosphamide and Methotrexate (AP-VC-MTX), was compared to two standard types of chemotherapy (Doxorubicin/Cyclophosphamide or Doxorubicin/Cisplatin) in a prospective, randomised study. The AP-VC-MTX regimen showed equal therapeutical results but had a significantly lower level of nephrotoxicity and gastrointestinal toxicity than the combined Doxorubicin/Cisplatin therapy. As a result of these studies we chose the AP-VC-MTX method as standard therapy for patients suffering from advanced stage ovarian carcinoma. Hormone therapy was tested in numerous phase II studies on patients who had previously received cytostatics and was found to be an effective alternative. One of the substances that was most closely studied was Medroxyprogesterone acetate (MPA). Its therapeutic value was established in in vitro tests which showed direct cytotoxicity in ovarian carcinoma and is based on the theory that, on the one hand, the MPA is attached to the progesterone receptor and impairs growth in a similar way to endometrium and breast carcinoma and, on the other hand, the MPA reduces the level of gonadotropin and estrogen, which may be factors, which stimulate tumour growth in ovarian cancer. Furthermore, the myeloprotective effect and the corticoid-like effect of the MPA usually result in lower bone marrow toxicity and an increase in weight. 81 in vitro chemosensitivity tests carried out on tumour-cell cultures of 25 patients suffering from ovarian carcinoma, showed sensitivity to Cisplatin in 38%, Doxorubicin in 44%, 4-OOH-Cyclophosphamide (the in vitro active metabolite of Cyclophosphamide) in 50%, Vincristine in 53%, MTX in 19% and MPA in 36%.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:[Combined chemo- and hormone-therapy in advanced ovarian carcinoma--theoretical, experimental foundations and clinical results]. 214 2

Previous articles have reported that the c-myb proto-oncogene was activated in various types of tumours of the hematopoietic system suggesting that this gene plays a role in the development of these malignancies. However no studies of the c-myb gene have as yet been performed in solid primary tumours. In the present study we have analysed in breast cancer the c-myb gene with the aim to determine its involvement in tumour progression. Expression of the c-myb oncogene was analysed from 169 carcinoma specimens obtained from untreated patients with non-inflammatory breast cancer (NBC) (112 patients) and inflammatory breast cancer (IBC) (57 patients). A 3.5 kb c-myb transcript band was detected in 108 (64%) tumours. c-myb expression was found to be associated with good prognostic factors (lowest histopathologic grade (P = 0.01), oestrogen and progesterone receptor status (P less than 10(-4)) and pS2 gene expression (P less than 10(-4)) and negatively correlated with breast cancers of poorer prognosis, namely IBC (P = 0.03) and NBC with multiple involved nodes (P = 0.15). Other genes (c-myc, c-erbB2, c-fos and epidermal growth factor receptor) were also studied. The c-myb gene expression was found to be inversely correlated (P less than 0.03) with only c-erbB2 overexpression in NBC. When data were analysed with a logistic regression model using a stepwise procedure, c-myb expression was found to be associated only with the oestrogen receptor status (P less than 10(-4)). In conclusion, our data indicate that analysis of c-myb expression in breast cancer could allow the characterization of a new class of oestrogen-dependent tumours.
 ...
PMID:Strong association between c-myb and oestrogen-receptor expression in human breast cancer. 218 74

Tumor samples of 26 consecutive colorectal carcinomas were studied for the presence of steroid hormone receptors for estrogen and progesterone. In all cases, the estradiol receptor binding capacity was below 2 fmol/mg cytosol protein. In 4 of 26 samples, progesterone receptor levels from 13 to 23 fmol/mg cytosol protein were observed. Because of the identification of steroid receptors in some cases and single reports in literature about tumor regression under hormone therapy of colorectal carcinoma, further investigations seem indicated to study the hormone sensitivity of colorectal carcinoma.
 ...
PMID:[Steroid hormone receptor status of colorectal cancers]. 218 19

Breast cancer specimens from 600 women were assayed for estrogen receptors (ER) using an immunocytochemical assay (ICA) employing the monoclonal antiestrophilin antibody H222 Sp gamma. Results showed significant correlation with biochemical ER determinations as well as with tumor grade and menopausal status. In 449 cases, results of progesterone receptor assay by ICA using the monoclonal anti-PgR antibody KD 68, also correlated significantly with biochemical PgR measurements. The ERICA/PgRICA positivity was significantly more frequent in postmenopausal white women. Colloid carcinomas were most likely to be ERICA positive and PgRICA positive whereas medullary carcinomas were most often negative. In 47 patients with advanced mammary carcinoma, results of ERICA and PgRICA were more closely related to endocrine response than those of ER and PgR by dextran-coated charcoal assay (DCC). In 339 women with Stage I or Stage II breast cancer, ERICA was significantly associated with disease-free survival. Analysis by Cox's proportional hazard model, however, showed PgRICA to be the best predictor of survival and disease-free survival in 197 women at the same stages of disease. These data indicate that ICA is more predictive of prognosis than biochemical ER and PgR. The ease of ICA performance coupled with these results indicate that the method is an acceptable substitute for DCC in analyzing breast cancers for ER/PgR.
 ...
PMID:Immunocytochemical estrogen and progestin receptor assays in breast cancer with monoclonal antibodies. Histopathologic, demographic, and biochemical correlations and relationship to endocrine response and survival. 220 20

The steroid hormone, progesterone, enhances transcription in vivo from promoters containing progesterone response elements (PREs). We have recently shown that the progesterone receptor (PR) modulates transcription in a cell-free system by facilitating the formation of a stable preinitiation complex, apparently through interaction with RNA polymerase II and other basic transcription factors. The precise role of ligand in this activation process remains unclear, however. In order to dissect the role of steroid ligand in gene action, we sought to devise an in vitro transcription system that mimics the hormone-dependent transcriptional activation observed in vivo. We now report the successful reconstitution in vitro of progesterone-dependent RNA synthesis from a PRE-driven promoter in nuclear extracts of human breast carcinoma (T47D) cells. The transcriptional activation is triggered by the hormone-induced binding of endogenous PR to PREs and exhibits hormone-specificity. The receptor exists in a 4S form in our initial salt-treated extract and is apparently dissociated from the heat-shock protein hsp90. Nevertheless, hormone is still required for DNA binding and transcriptional activation. These results suggest that dissociation of hsp90 and conversion to an inactive 4S intermediate could occur before the final event in ligand-mediated transactivation of gene expression.
 ...
PMID:Identification of a functional intermediate in receptor activation in progesterone-dependent cell-free transcription. 234 63


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