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Biomedical subjects

M E Lippman

Publications and source records attributed to M E Lippman.

At least 307 records · Page 17Linked to original sources
PubMed1979

Direct inhibition of growth and antagonism of insulin action by glucocorticoids in human breast cancer cells in culture.

We have examined the interaction of dexamethasone with the ZR75-1 human breast cancer cell line to determine if glucocorticoids might directly inhibit growth of breast cancer cells. Growth of these cells in serum-free medium was stimulated significantly by physiological concentrations of insulin (0.1 to 1.0 nM). Pharmacological concentrations of dexamethasone (10 nM) reduced cell number below that found in controls and nearly abolished the effect of insulin after several days in culture. Thymidine and uridine, but not leucine, incorporation into macromolecules or acetate incorporation into fatty acids were similarly inhibited by dexamethasone in the presence of absence of insulin. Dexamethasone did not inhibit insulin effects by altering insulin receptor affinity or concentration, as determined by Scatchard analyses of insulin binding. Net thymidine uptake into the trichloroacetic acid-soluble fraction of the cell was stimulated by insulin and inhibited by dexamethasone also inhibited thymidine kinase activity multiple potential sites of glucocorticoid action that directly oppose the effects of insulin. They also suggest that glucocorticoids have a direct inhibitory effect on proliferation of human breast cancer cells, which may help explain breast tumor regression following pharmacological glucocorticoid therapy.

Acetates↗
PubMed1979

Prolonged retention of estradiol by human breast cancer cells in tissue culture.

Conditions are described under which prolonged estradiol retention and estrogenic activity are observed in human breast cancer cells in tissue culture. The cells were incubated for three hr with a physiological concentration of [3H]estradiol (3 to 5 nM) and then were washed with 3 successive exchanges of medium 3, 17, and 24 or 48 hr following incubation with [3H]estradiol. The total wash period was 78 hr. The following parameters were monitored to assess the duration of estrogen action in MCF-7 human breast cancer cells in tissue culture; (a) the concentration of [3H]estradiol and [3H]estradiol metabolites in the media washes; (b) the intracellular concentration of [3H]estradiol and [3H]estradiol metabolites; and (c) the time course of estradiol-enhanced rates of radiolabeled thymidine incorporation. The [3H]estradiol concentration in the final medium wash was approximately 0.05 nM. The total intracellular concentration of tritium was about 50 nM prior to wash and 9 nM following 78 hr of wash. The intracellular concentration of specifically bound [3H]estradiol was initially 18 nM, and after 78 hr of wash, it was 2.8 nM. After 48 hr of wash, nearly all specifically bound [3H]estradiol was present in the nucleus. Following incubation of the cells with 5 nM estradiol and an identical wash procedure, estrogenic activity as measured by a stimulation of thymidine incorporation was observed throughout the 78 hr monitored. When 10(-6) M tamoxifen or 10(-7) M unlabeled estradiol was included in the medium washes, the washout of nonspecific binding was unaffected; however, specifically bound [3H]estradiol was essentially eliminated within 24 hr. When bovine serum albumin was included in the medium washes, total, nonspecific, and specific [3H]estradiol binding was reduced in a parallel and dose-dependent fashion. After 48 hr, cells washed with medium containing 3.5 or 7% bovine serum albumin contained one-tenth of the [3H]estradiol present in cells washed with medium alone. We conclude that medium exchanges alone do not effectively remove estradiol from MCF-7 cells, and suggest that estrogen retention by estrogen-responsive cells may mask in vitro assessments of such responsiveness in this and other systems. Inclusion of bovine serum albumin in the washes may alleviate this problem.

Breast Neoplasms↗
PubMed1979

Association between steroid hormone receptor status and disease-free interval in breast cancer.

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.

Adult↗
PubMed1978

[Induction of glucocorticoid hormone receptors in continuous human T-lymphocyte cultures (proceedings)].

The presence is documented of high levels of specific glucocorticoid hormone receptors in human cultured T cells (CTC) maintained with a conditioned medium. When conditioned medium was removed from CTC for 24 h, receptor levels reverted to those of fresh, unstimulated lymphocytes. When conditioned medium, or phytohemagglutinin, was then added at various times before testing for glucocorticoid receptors, these stimuli were shown gradually to induce more receptor activity, beginning at about 10 h of stimulation and increasing to 10-fold through 24 h.

Cells, Cultured↗
PubMed1978

The relation between estrogen receptors and response rate to cytotoxic chemotherapy in metastatic breast cancer.

In a retrospective study we determined the relation between estrogen receptors and the response rate to cytotoxic chemotherapy in 70 patients with metastatic breast cancer. Thirty-four of 45 patients with low or absent estrogen-receptor values (less than 10 fmol per milligram of cytoplasmic protein) had objective responses to chemotherapy, whereas only three of 25 patients with higher values (greater than 10 fmol per milligram of cytoplasmic protein) responded (P less than 0.0001). There were no statistically significant differences between the two groups in age, menopausal status, disease-free interval, Karnofsky index or prior therapy. Differences in sites of involvement or type of chemotherapy did not account for the increased response rate in receptor-negative patients. We conclude that estrogen-receptor values are an important predictor of response to cytotoxic chemotherapy in metastatic breast cancer.

Adult↗
PubMed1978

Hepatic estrogen and progesterone receptors in an estrogen-associated hepatic neoplasm.

A patient with a benign hepatic neoplasm developing after treatment with estrogenic hormones is described. After excision, the neoplastic tissue was analyzed for the presence of cytosol estrogen and progesterone binding proteins. The neoplasm was classified as focal nodular hyperplasia of the liver and was demonstrated to contain high-affinity cytosol estrogen and progesterone hormone receptors. The estrogen-binding affinity of the neoplasm was three times greater than that of normal liver. Further investigation of cytosol hormone receptors in estrogen associated hepatic neoplasms will be required to define the role of these binding proteins in the possible etiology of certain liver tumors.

Clinical Trials as Topic↗
PubMed1978

Failure of breast cancer cells in long-term culture to aromatize androstenedione.

The ability of breast cancer cells in long-term tissue culture to aromatize androstenedione to estrone and estradiol was examined. (3H) androstenedione (1.1 x 10(-7)M) was incubated with 9 cell lines of human breast cancer and one line derived from a dimethylbenz(a)anthracene induced rat mammary tumor. No conversion to estrone or estradiol was detected. The findings are discussed in light of previous studies showing aromatization of androgens in breast cancer tissues.

Androstenedione↗
PubMed1978

Growth of a human breast cancer cell line in serum-free hormone-supplemented medium.

ZR-75-1, a human breast cancer cell line, has been grown in hormone-supplemented medium without serum. The factors required for optimal growth include 17beta-estradiol, insulin, transferrin, dexamethasone, and L-triiodothyronine. If estradiol, insulin, or L-triiodothyronine is omitted, cells cease division within 7 days, but viability is retained for at least 14 days. Omission of transferrin leads to cell death within 7 days. The cells have been continuously maintained in this environment without morphological alteration or cessation of growth for more than 5 months. Addition of the anti-estrogen, Tamoxifen (10(-6) M), inhibited cells below the growth rate seen when estradiol was omitted from the medium, even when Tamoxifen was added 4 days and two medium changes after the removal of estradiol from the medium, thus suggesting an action of Tamoxifen which may be independent of competition with estradiol. The availability of a human breast cancer cell line that can be propagated in hormone-supplemented medium without serum should aid in the study of the mechanisms by which hormones effect cell growth.

Breast Neoplasms↗
PubMed1978

Clinical implications of glucocorticoid receptors in human leukemia.

Glucorticoid receptors were studied in various populations of normal human peripheral blood lymphocytes and leukemic lymphoblasts. Normal lymphocytes contain low levels of glucocorticoid receptor (approximately 2,500 sites/cell) which are identical in T- and non-T-fractions. Phytohemagglutinin treatment increases levels about 3-fold. Leukemic lymphoblasts contain larger numbers of receptor sites. Presence of receptor is correlated with in vitro sensitivitiy to glucocorticoids and in vivo response to therapy. Quantity of receptor is also correlated with complete remission duration independently of leukemic cell type (T or null), initial WBC, or age of patient. Quantitative determination of glucocorticoid receptor levels in acute lymphoblastic leukemia may be of value both as an independent prognostic variable and in suggesting which patients should receive glucocorticoid therapy.

Adolescent↗
PubMed1978

Tamoxifen retinopathy.

Tamoxifen has been used as a chemotherapeutic agent with no serious side effects noted. Four patients receiving high-dose tamoxifen for greater than 1 year have demonstrated similar retinal changes. Three of the four patients had a significant decrease in visual acuity as the result of a retinopathy, primarily affecting the region about the macula accompanied by macular edema. In addition, three of the four patients had unusual corneal changes. These findings suggest that the corneal and retinal changes are the result of a toxic effect of tamoxifen when used in the doses and duration described.

Aged↗
PubMed1978

Establishment and characterization of three new continuous cell lines derived from human breast carcinomas.

Three continuous lines of mammary tumor cells (ZR-75-1, ZR-75-27, and ZR-75-30) have been established from malignant effusions of two women with breast cancer. Differentiated properties expressed by each cell line include: (a) epithelial morphology (by light and electron microscopy) resembling that of the parental tumors; (b) presence of receptors for estrogen and other steroid hormones; and (c) growth responsiveness to estrogen and/or progesterone. All three cell lines possess human karyotypes that differ from one another in modal chromosome number as well as in characteristic marker chromosomes. Two of the cultures (ZR-75-27 and ZR-75-30), although derived from the same patient, have stable differences in their karyotypes.

Breast Neoplasms↗
PubMed1978

Association between steroid hormone receptors and response rate to cytotoxic chemotherapy in metastatic breast cancer.

The influence of steroid hormone receptors on response rate to cytotoxic chemotherapy in 70 patients with metastatic breast cancer was determined in a retrospective study. We have previously reported that 34 of 45 patients with tumors containing low or absent estrogen-receptor values had objective responses to chemotherapy while three of 25 patients with positive estrogen-receptor tumors responded. In the present study, 22 of 34 patients with low or absent progesterone-receptor tumors had an objective response to cytotoxic chemotherapy, while none of eight patients with a positive progesterone-receptor tumor responded (P less than 0.05). Patients having tumors with a negative estrogen receptor and a negative progesterone receptor had a response rate of 88% (21 of 24 patients). There were three patients whose tumors were estrogen-receptor negative but progesterone-receptor positive; none had a response to chemotherapy. Chemotherapy response was not associated with the presence or absence of either androgen or glucocorticoid receptor. We conclude that progesterone-receptor values in addition to estrogen-receptor status may prove to be important correlates of response to cytotoxic chemotherapy in metastatic breast cancer. Androgen- and glucocorticoid-receptor analyses are not helpful in predicting response to chemotherapy.

Adult↗