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Biomedical subjects

M E Lippman

Publications and source records attributed to M E Lippman.

At least 325 records · Page 18Linked to original sources
PubMed1977

Steroid hormone receptors in normal human lymphocytes. Induction of glucocorticoid receptor activity by phytohemagglutinin stimulation.

The presence of specific steroid hormone receptors in human lymphocytes was investigated in unstimulated and phytohemagglutinin-stimulated glass wool column-purified peripheral blood lymphocytes. Specific steroid binding in intact cells was determined by a whole cell competitive binding assay. Non-phytohemagglutinin-stimulated lymphocytes had about 2700 specific glucocorticoid binding sites per cell; phytohemagglutinin stimulation induced a 2 to 3-fold increase in glucocorticoid receptor activity within 16 h of culture. No estrogen, androgen, or progestin binding sites were detected in either unstimulated or phytohemagglutinin-stimulated peripheral blood lymphocytes. Scatchard analysis of glucocorticoid binding was consistent with a single class of receptor sites with a dissociation constant (Kd) of about 5.5 x 10(-9) M (correlation coefficient r = -0.96). Significant competition for radiolabeled dexamethasone binding was not observed with steroids lacking glucocorticoid activity. There was good agreement between relative binding affinities of various steroids to glucocorticoid receptor in lymphocytes and ability of these steroids to inhibit phytohemagglutinin-stimulated thymidine incorporation.

Binding Sites↗
PubMed1977

The measurement of androgen receptors in human prostatic tissue utilizing sucrose density centrifugation and a protamine precipitation assay.

Methods have been established for the measurement of androgen receptors in the cytosol and crude nuclear extract of human prostatic tissue using sucrose density gradient centrifugation and a protamine precipitation assay. These studies have demonstrated the presence of a high affinity, heat labile protein that binds preferentially to dihydrotestosterone and that is present only in androgen target tissues. In studies of prostatic tissue from 15 patients sucrose density gradient centrifugation appeared more sensitive than the protamine precipitation assay in the identification of androgen receptors. These findings appear promising and suggest that in the near future a reliable assay may be available for the measurement of androgen receptors in prostatic carcinoma.

Centrifugation, Density Gradient↗
PubMed1977

Insulin stimulation of fatty acid synthesis in human breast cancer cells.

Four human breast cancer cell lines were tested for their response to hormones with respect to the lactational function, fatty acid synthesis. Physiologic concentrations of insulin enhanced the incorporation of [14C]acetate into fatty acids in two of four cell lines tested. All cell lines had specific, high-affinity insulin receptors; therefore, the failure of two lines to respond could not be attributed to the absence of receptor. The effect of insulin involved an increase in the maximun velocity of incorporation rather than a decrease in the Michaelis constant.

Acetates↗
PubMed1977

Variants of HTC cells with low tyrosine aminotransferinase inducibility and apparently normal glucorticoid receptors.

Variants of HTC cells showing little or no induction of tyrosine aminotransferase in response to glucorticoids have been isolated by repeated cloning without deliberate selective pressures. In this paper, the derivation and some properties of these cells, compared with both high-inducing clones and wild-type cells, are described. The non-inducing cells all grew well, and were not induced even by unusually high concentrations of steroid. The enzyme activity had a normal half-life of decay and heat inactivation. It was inactivated by antiserum against authentic tyrosine aminotransferase, and no evidence for antigenically active, enzymatically inactive enzyme was found. No great variability was seen in the few other enzyme activities tested. Glucorticoid receptors were present in all the clones, With respect to concentration, cellular uptake, cell-free binding to nuclei and intracellular localiztion, no differences were found between the receptors of inducible and non-inducible clones. These are the first cells derived from an inducible type to be characterized as having normal receptor while becoming steroid resistant. They appear to be blocked in a late step of the response to the steroid, and therefore may prove useful in analyzing these later steps.

Aspartate Aminotransferases↗
PubMed1977

Insulin stimulation of fatty acid synthesis in human breast cancer in long term tissue culture.

The effect of various steroid and peptide hormones on the rate of incorporation of (14C)acetate into fatty acids was studied in MCF-7 cells, a human breast cancer cell line in continuous tissue culture. Physiologic concentrations of insulin elicited an increase in the rate of precursor incorporation. Addition of human placental lactogen and dexamethasone with insulin caused no further increment. Other hormones, such as 17beta-estradiol and 15a-dihydrotestosterone, had no effect on the rate of net labeled-acetate incorporation, although they stimulated the rate of general macromolecular synthesis. The stimulation by insulin appeared to be independent of glucose concentration, since the effect was seen in the absence of glucose. The insulin-induced increase was observed as early as 1 h following hormone addition and appeared to be maximal by 4 h. Inhibitors of RNA and protein synthesis had no effect on the insulin-mediated stimulation of precursor incorporation into fatty acids. Thus, these human cell lines in long term tissue culture may be of value as a model system in studying the action of physiologic concentrations of insulin.

Acetates↗
PubMed1977

Casein production by human breast cancer.

Casein was measured in the sera of breast cancer patients, in breast cancer tumors, and in breast cancer cells in long-term tissue culture using a sensitive and specific radioimmunoassay. Levels present in breast cancer sera were not elevated above control values. Eight of forty-seven (17%) of the tumor samples tested were positive for casein, the highest level representing 0.003% of the soluble protein. When seven human breast cancer cell lines were assayed for casein, the results were uniformly negative even under conditions of stimulation by lactogenic hormones. In addition, direct immunoprecipitation of labeled cellular protein supported the negative result of the radioimmunoassay. Thus it appears that casein production is not a common characteristic of most human breast cancers.

Breast Neoplasms↗
PubMed1976

Oestrogen receptors in human malignant melanoma.

16 of 35 patients (46%) with malignant melanoma were found to have cytoplasmic oestrogen-receptor activity in biopsy specimens. OEstrogen-receptor activity was detected in primary lesions, lymph-node metastases, skin metastases, and visceral metastases. Equal percentages of males and females had positive assays. Scatchard analysis of binding in one case was consistent with a single class of high affinity receptor sites.

Adult↗
PubMed1976

Mediastinoscopy: a diagnostic aid in metastatic carcinoma of the breast.

Six patients with metastatic carcinoma of the breast underwent mediastinoscopy to obtain tissue for estrogen receptor analysis and pathologic confirmation of metastatic tumor. The indication for mediastioxcopy was an abnormal mediastinal accumulation of gallium in five patients, only two of whom had an abnormality noted on tomography. All six patients had tumor recovered by mediastinoscopy as demonstrated by pathologic examination and/or estrogen receptor assay, Therefore, the diagnosis of mediastinal metastases in breast cancer may be suggested by either chest roentgenograms, mediastinal tomography, or gallium scintigraphy. Mediastinoscopy is a safe, effective procedure capable of establishing the diagnosis of metastatic carcinoma of the breast and of procuring sufficient tissue for estrogen receptor analysis in patients without more readily accessible sites of metastases.

Adult↗
PubMed1976

Hormone responsive human breast cancer in long-term tissue culture: effect of insulin.

The mechanisms of steroid and peptide hormone action in human breast cancer are poorly understood. We have previously characterized a cell line of human breast cancer in long-term tissue culture that possesses various steroid hormone receptors and responses, providing a model for the study of steroid hormone action. The present studies describe a human breast cancer in vitro that responds to physiologie concentrations of insulin with an increased rate of macromolecular synthesis and growth. Thymidine and uridine incorporation in cells in serum-free medium are stimulated by 10(-11) M insulin and are maximal with 10(-8) M. Leucine incorporation is stimulated by 5 X 10(-11) M insulin and is maximal with 10(-9) M. Significant stimulation of uridine and leucine incorporation is evident by 3 hr and maximal by 10 hr. A 10-hr lag period exists for insulin stimulation of thymidine incorporation, which is maximal form 14 to 24 hr. The effect of 10(-8) M insulin on macromolecular synthesis is accompanied by a 69% increase above controls in the number of cells after 24 hr. The effect on macromolecular synthesis is observed in glucose-free medium. Insulin's effect on protein synthesis is not blocked by inhibition of RNA synthesis with actinomycin D. Glucocorticoids partially inhibit the action of insulin in these cells. This system provides a model for studying insulin action, and suggests that some human breast cancer may show growth regulation by insulin.

Breast Neoplasms↗
PubMed1976

Evaluation of tamoxifen dose in advanced breast cancer: a progress report.

The results of an ongoing trial randomizing patients with progressive, metastatic breast carcinoma between tamoxifen (Tam, NSC-180973) and Tam plus fluoxymesterone (Flu) (7 mg/m2 bid) are reported. Each patient received a single dose level of Tam in the range of 2-100 mg/m2 bid. The combination had a higher response rate overall (45% vs 28%) and when only the patients' soft tissue sites were analyzed (54% vs 9%, P=0.04). The time to treatment failure was longer for the combination among those patients with a response or disease stabilization (P=0.08). Response rates with Tam doses less than 12 mg/m2 bid were also higher than with doses greater than or equal to 12 mg/m2 for all patients in the study (62% vs 30%, P=0.025) and for those where only soft tissue sites were evaluable (43% vs 29%, P=0.07). Side effects were mild and consisted primarily of transient hematologic suppression, nausea, masculinization, hepatic enzyme elevations, and edema. The latter three were observed only with the Flu regimen. Leukopenia and thrombocytopenia were more frequent at Tam doses less than 12 mg/m2 bid whereas nausea was more common at higher doses. Tam doses as high as 100 mg/m2 bid were well tolerated. Tam amy be more effective at low doses, has only mild side effects, and is well tolerated at doses up to 100 mg/m2 bid. Combining Tam with Flu appears to enhance the therapeutic effectiveness.

Adult↗
PubMed1976

Evaluation of an intermittent schedule of dibromodulcitol in breast cancer.

Dibromodulcitol was administered orally on Days 1-10 every 3-4 weeks to 29 patients with metastatic breast carcinoma refractory to previous combination chemotherapy. Initial doses between 70 and 280 mg/m2/day were utilized. The dose was escalated as tolerated in subsequent cycles in individual patients. Hematosuppression was dose-limiting. At doses of greater than 200 mg/m2/day leukopenia (greater than 1000 cells/mm3) and thrombocytopenia (greater than 25,000 platelets/mm3) occurred in one of 28 cycles and two of 27 cycles respectively. In contrast, at doses of less than or equal to 200 mg/m2/day leukopenia and thrombocytopenia occurred in four of 18 cycles and five of 18 cycles respectively. Recovery of leukocytes (less than 4000 cells/mm3) and platelets (less than 100,000 platelets/mm3) by Day 29 after the start of therapy was also delayed at higher doses. Responses were observed in three of 29 evaluable patients and subjective improvement of osseous disease in one additional patient. A dose of 180 mg/m2/day X 10 Every 28 days is recommended in previously treated patients to avoid severe hematologic side effects.

Adult↗
PubMed1975

Serum-free growth of HTC cells containing glucocorticoid- and insulin-inducible tyrosine aminotransferase and cytoplasmic glucocorticoid receptors.

HTC cells have been made to grow in chemically defined medium without any macromolecular supplements whatsoever. Initial estimates of their relative amino acid requirements have been made. The cells grown in the defined medium retain many of the differentiated features which have been the focus of investigation in their serum-grown counterparts. Thus, the cells in defined medium contain cytoplasmic glucocorticoid receptors and have tyrosine aminotransferase which can be induced by glucocorticoids, serum or insulin. These cells also produce, in small amounts, an as yet undefined rat serum protein.

Cell Survival↗