Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

From the first day of dimethylbenzanthracene administration, daily treatment with 8 or 24 mug of the new antiestrogen 11alpha-methoxy ethinyl estradiol (RU 16117) completely prevented the appearance of mammary tumors in all animals up to the last time interval studied (130 days after dimethyl benzanthracene administration). At daily doses of 0.5 and 2.0 mug RU 16117, the tumor incidence was reduced to 78.6 and 40%, respectively. Not only was the number of animals developing tumors reduced after injection of low doses of RU 16117, but the number of tumors per rat and the size of tumors were also markedly reduced. The levels of receptors for estradiol, progesterone, and prolactin in tumor tissue were reduced after treatment with 2.0 mug RU 16117, while the binding of growth hormone and insulin was not affected. Whereas plasma luteinizing hormone levels decreased after treatment with 8 or 24 mug RU 16117, plasma prolactin levels slightly increased in animals receiving the highest dose of the antiestrogen. It is thus likely that the potent inhibitory effect of RU 16117 on the development of dimethylbenzanthracene-induced mammary tumors results from actions at both the hypothalamic-pituitary and the tumor (mammary gland) levels, the action at the peripheral level possibly being secondary to a reduced sensitivity of the tissue to circulating hormones through lowering of hormone receptor concentrations.
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PMID:High inhibitory activity of a new antiestrogen, RU 16117 (11alpha-methoxy ethinyl estradiol), on the development of dimethylbenz(a)anthracene-induced mammary tumors. 18 38

Predictive tests assisting in selection of breast cancer patients for endocrine therapy have been reviewed. Information gained from histologic sections, such as degree of the tumor differentiation, degree of elastosis, Barr-body count and the DNA content, are valuable predictors of prognosis and response to endocrine therapy. The length of time between mastectomy and recurrence of metastasis is an important factor in predicting response to ablative endocrine surgery. The presence of various enzymes in the tumor tissue, blood groups, immunologic competence, altered metabolism of tryptophan, urinary excretion of steroids and in vitro hormonal responsiveness of the tumor tissue have not been widely used as predictors of tumor response to endocrine therapy. The determination of hormone receptors in primary or metastatic breast tumors is at present the most reliable test in selecting breast cancer patients for endocrine therapy. Future developments in hormone receptor assay may provide a means of tailoring endocrine therapy to the individual patient.
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PMID:[Selection of patients with breast cancer with regard to endocrine therapy]. 19 40

There are indications that the status of hormone receptors in breast cancer tissue is related to the success of chemotherapy to treat breast cancer. Remissions are recorded in 60% of the cases of endocrine treatment of patients with positive evidence of cytoplasmic hormone receptors. It must be kept in mind, however, that any given cancer tissue sample is not representative for all metastases locations. Depending on the hormone receptor content of each section, different parts of the tumor could react differently to hormone treatment, and even sections with the same receptor content can react differently to treatment. The criteria for the determination of a remission are too strict. The carbon absorption method or the more common agargel electrophoresis can be used to determine the level of receptor content in a tissue sample.
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PMID:[Hormone receptors and breast carcinoma]. 22 Nov 63

To determine the hormone-dependence of a tumor, it is preferable to use highly specific radiolabeled ligands when available, since often more than one class of steroid hormone receptor is present in the tissue specimen, and interference from classes other than the one under study cannot be readily eliminated. In this study, we describe a simple in vitro system used to define the molecular requirements for a highly specific interaction between a steroid and the receptor corresponding to a single class of hormone. It is based on the use of homogenate or crude 105,000 X g supernatant prepared from the target organs considered as end points in routine biological potency tests and on the use of available radioligands not bound by plasma proteins (tags) to single out the receptors. For each receptor singled out in the target organ cytoplasm, the ability of over 700 molecules to decrease bound radioactivity was compared to that of the natural hormone (relative binding affinity) with the use of a dextran-coated charcoal technique to separate bound from unbound steroid. On the basis of the results on 81 molecules, presented in this study, the effect of various substituents on the affinity and specificity of the natural hormones was determined. Molecules interacting markedly with several receptors were submitted to X-ray crystallography in order to establish whether overlap between the various conformations of the natural hormone and of the test molecule might not partly account for lack of specificity.
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PMID:Unique steroid congeners for receptor studies. 35 34

Additive hormonal therapy remains the treatment of choice for disseminated breast cancer in postmenopausal women. Patients with hormone-dependent tumors receive excellent and long-lasting palliation from alterations in the hormonal milieu. Now that hormone receptor assays are clinically available, responses can be accuratedly predicted in a large percentage of cases. Tables 11--6 is a summary of additive hormonal therapy in postmenopausal patients. Endocrine ablative therapy remains of primary importance in premenopausal women because of the superior results, but androgens or antiestrogens may be helpful when patients are not surgical candidates. Castration continues to be the initial approach, with adrenalectomy or hypophysectomy reserved for promising candidates. In postmenopausal women the initial choice is estrogens. The exceptions are those patients with metastases limited to bone, when androgens excel because of an equivalent objective response and superior subjective and metabolic effects. Patients who respond to estrogens and then progress are observed for a rebound regression following the discontinuation of estrogen therapy. Whereas some who do not respond to androgens will respond to estrogens, the converse does not appear to be true (Kennedy, 1974). Currently progestins are the secondary hormonal agent of choice in postmenopausal women, but they may be displaced by antiestrogens as more data become available. In general, if a patient's tumor lacks estrogen receptors or the patient fails to respond to an adequate trial of endocrine or hormonal therapy, one should proceed directly to cytotoxic chemotherapy. A suggested plan for the integration of endocrine with hormonal therapy and both with other forms of palliation is diagrammed at the end of Chapter 12.
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PMID:Cancer of the breast. Endocrine and hormonal therapy. 37 52

This article reviews the contribution of steroid hormone receptor studies to the resolution of a basic clinical problem: how to determine which cancers are hormone dependent without an actual treatment trial. Previously published studies on hormone receptor assays and analyses are reviewed, the current status of knowledge in the area is summarized in terms of its relevance to breast cancer cells, and future scenarios are proffered. Assay methods and available clinical results for cytoplasmic estrogen receptor identification in human breast cancer comprise the first section. Information on assaying nuclear estrogen receptor, and its relative clinical importance, is presented in Part 2. Assays to determine the presence of progesterone receptor in human breast cancer; the estogen regulation of such progesterone receptors; and clinical findings comprise Part 3. Studies of the mechanisms of estrogen action in the MCF-7 human breast cancer cell line are the subject of Part 4. Recent experiments in animals on the efficacy of antiestrogen treatments, such treatments in human in vitro cell cultures, and the few clinical trials available are presented in Part 5. It is emphasized that the simple presence or absence of estrogen receptors in tumors does not absolutely indicate whether growth of a particular tumor is sensitive to estrogens. Experimental appraoches, designed to further delineate this problem, are outlined, based on observations such as the finding that the probability of tumor regression correlates better with quantitative rather than with qualitative assessment of estrogen receptors; that the specific end product of hormone action is unknown and without this information an ideal biochemical marker to a tumor's sensitivity of hormones is unavailable; and that the complex sequence of biochemical events in the actions of estrogen needs more complete elucidation.
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PMID:Estrogen and progesterone receptor proteins in breast cancer. 39 Dec 86

This study describes the distribution and frequency of estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), and glucocorticoid receptor (GR) in a large series of patients with primary metastatic breast cancer. 329 patients were in this series. All 4 steroid hormone receptors were present in the population: ER was positive in 53%, PR was positive in 38%, AR was positive for 31%, and GR was positive in 52%. Next, the distribution of ERs as well as the distributions of PR, AR, and GR values seemed unimodal. There was a very high correlation between any steroid hormone receptor value expressed as either fmol/mg of cytoplasmic protein or fmol/mg of breast tumor. Of more importance was that alternate methods of data expression did not alter the classification of values as positive or negative. No correlation was found between any of the steroid hormone receptors and laterality of the breast tumor, location and size of the primary tumor, extent of disease, or type of tissue assayed. None of the steroid hormone receptors correlated with age. There was a strong correlation noted between ER values and menopausal status. Neither PR, AR, nor GR was significantly associated with menopausal status. ER status was correlated with axillary nodal status, with the ER positive group containing a high proportion of node-negative patients. Finally, quantitative analysis of steroid receptor hormone values demonstrated correlations among other receptors. Plotting values of any 1 receptor vs. any other receptor resulted in a positive Kendall rank test correlation which was highly significant.
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PMID:Distribution, frequency, and quantitative analysis of estrogen, progesterone, androgen, and glucocorticoid receptors in human breast cancer. 42 88

85 patients with metastatic or surgically unrecsectable primary breast cancer who had had 1 or more steroid hormone receptor assays performed immediately before the institution of endocrine therapy were studied retrospectively to determine any influence of steroid hormone receptors on response rate to endocrine therapy. Included in addition to effects of estrogen receptor (ER) status are the effects of androgen receptor (AR), progesterone receptor (PR), and glucocorticoid receptor (GR) on therapy perfornamce. Of 18 patients whose tumor contained PR, 11 responded to endocrine therapy, compared with 8 of 26 patients with low or absent PR. PR increased the predictive index of the ER in an group of patients who had received no prior therapy, but it did not help in patients who had received prior endocrine therapy. 0 of 4 patients whose tumors were ER negative but PR positive responded to endocrine therapy. Present trends suggest a possible association between AR and GR and response to endocrine therapy. A cut-off value of 10 fmol/mg of cytoplasmic protein was needed to make these trends apparent. The distributions of AR and GR values for responders and nonresponders were not significantly different. Knowledge of AR status does not increase the protective index in ER-positive or ER-negative tumors. GR positivity may increase the predictive index in ER-positive tumors, but not in ER-negative ones.
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PMID:Relationship between the progesterone, androgen, and glucocorticoid receptor and response rate to endocrine therapy in metastatic breast cancer. 44 96

The possibility of an association between steroid hormone receptor status and disease-free interval was examined in 292 patients with breast cancer. Estrogen receptor positivity was associated with a prolonged disease-free interval. This association was independent of age, menopausal status, tumor size, or nodal status. There was no association between the presence or absence of progesterone, androgen, or glucocorticoid receptor and disease-free interval.
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PMID:Association between steroid hormone receptor status and disease-free interval in breast cancer. 47 5

Several histologic variants of the transplantable R-3327 prostatic adenocarcinoma carried in male Copenhagen rats have been characterized and the histologic types have been correlated with steroid hormone receptor content. One type is clearly an adenocarcinoma; this tumor is hormonally responsive and contains substantial amounts of both androgen and estrogen receptors. In contrast, another histologic type, a fibrosarcoma, is hormonally nonresponsive and does not contain either receptor. A third histologic variant is classified as a carcinosarcoma and contains histological elements of both adenocarcinoma and fibrosarcoma and is also hormonally responsive. This tumor contains lower receptor levels than the adenocarcinomas but more than the fibrosarcomas. The androgen receptor appears to be identical in the different histologic forms of the tumor: the sedimentation coefficient is 7.8S and the dissociatiln constant for methyltrienolone is 4 x 10(-9) M. Similarly, the estrogen receptor from the different histologic forms of the tumor has a sedimentation coefficient of 8.3S and the dissociation constant for estradiol is 7 x 10(-10) M. These findings clearly distinguish the cytosol binding macromolecules from plasma binding proteins, and classify them as steroid hormone receptors. Further, rat serum was devoid of androgen and estrogen binding in the 8S region. Normal prostate tissue from Copenhagen rats contained low levels of an androgen receptor, but no estrogen receptor. It is possible that during growth and/or passage of the R-3327 tumor, the hormonally responsive adenocarcinoma cells do not survive and there is a gradual emergence of the nonresponsive fibrosarcoma. If, as we suspect, the receptors are found in the epithelial cells and not the stromal cells, there clearly should be considerable variation of receptor content in the different intermediary histologic forms of the tumor.
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PMID:Steroid hormone receptor characterization of several histologic variants of a rat prostatic adenocarcinoma. 75 Jul 63


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