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Biomedical subjects

M E Lippman

Publications and source records attributed to M E Lippman.

At least 289 records · Page 16Linked to original sources
PubMed1980

A dispersed-whole cell method for the determination of androgen receptors in human skin fibroblasts.

A method is described for the determination of binding capacity (Ro) and dissociation constant (Kd) of androgen receptors in dispersed, whole, cultured human skin fibroblasts. The cells obtained from punch biopsies or operative specimens of skin, are grown to confluence in monolayers, harvested, washed, and dispersed in medium. Binding is assessed by incubating the cells with [3H]dihydrotestosterone (DHT) at 22 degrees C for one hour followed by washing, centrifugation and counting. Non-specific binding is determined by adding radioinert methyltrienolone (R1881). Scatchard plots are constructed using 6 concentration points; binding is expressed as sites/cell. The method is precise (Ro = 12,105 +/- 4305 (S.D.) sites/cell; Kd = 1.0 +/- 0.7 (S.D.) x 10(-9)M, n = 14 for one prepuce cell line) and independent of cell passage number. Binding is linear with respect to cell number and shows those characteristics commonly attributed to androgen receptors: high affinity, low binding capacity, saturable nuclear binding, androgen specificity, and an 8S peak in fibroblast cytosol using sucrose density gradients. Cell lines shown by other published methods to lack androgen receptors had no detectable DHT binding with this method. This assay technique has the advantages of simplicity, rapidity, and precision.

Breast Neoplasms↗
PubMed1980

Binding of retinoids to human breast cancer cell lines and their effects on cell growth.

Vitamin A and its analogues (retinoids) regulate the differentiation of epithelial tissues. Retinoids inhibit the induction of rat mammary cancers by carcinogens in vivo, and cellular binding proteins for retinoids have been demonstrated in some human breast cancer samples. In this study, we examined the model system of human breast cancer cell lines in long-term tissue culture for effects of retinoids on growth and for the presence of cellular retinoid binding proteins. Retinoic acid and retinol inhibit the growth of of MCF-7, Hs578T, and ZR-75-B cell lines. Retinoic acid is more potent than retinol in this regard: 50% growth inhibition is achieved by 6 nM retinoic acid in ZR-75-B and by 700 nM in MCF-7 and Hs578T, whereas 5-8 muM retinol is required in all three cell lines. The time to onset of growth inhibition varies markedly between cell lines and is not related to cell density or doubling time. Retinoic acid increases the doubling time of MCF-7 and ZR-75-B by two- to threefold, but causes cell death in Hs578T. The growth inhibition is reversible in every cell line by removal of retinoic acid. Specific and distinct binding of [(3)H]retinoic acid and [(3)H]retinol is present in cytosols of MCF-7 and Hs578T cells as assessed by sucrose density gradient centrifugation. In ZR-75-B, [(3)H]retinoic acid binding was present, but no binding of [(3)H]retinol was detectable. This study reveals that retinoids may play an important role in the regulation and treatment of human breast cancer and that human breast cancer cell lines represent a useful model to study this role.

Breast Neoplasms↗
PubMed1980

Glucocorticoid sensitivity and receptors in cells of human myelogenous leukemia lines.

The effect of dexamethasone on the clonal proliferation of human acute myelogenous leukemia cells was studied using the two available human acute myelogenous leukemia lines KG-1 and HL-60. The cells were cloned in agar in the presence of colony-stimulating activity with and without dexamethasone. Colony formation by KG-1 cells was inhibited by dexamethasone at a concentration of 10(-7) M, and a 50% reduction occurred at 10(-5) M dexamethasone. Dexamethasone had no effect on HL-60 colony formation. Direct assessment of dexamethasone binding showed that both KG-1 and HL-60 cells had high-affinity glucocorticoid receptors with a mean 10,300 and 15,600 binding sites/cell with a Kd of 3.3 x 10(-9) M and 4.2 x 10(-9) M (r greater than or equal to -0.95), respectively. Binding competition studies confirmed the specificity of these glucocorticoid receptors. No correlation was noted between the number of glucocorticoid receptors and the in vitro inhibition of colony formation. A variety of other steroids was tested and found to have no effect on clonal proliferation of the leukemic cells.

Binding, Competitive↗
PubMed1980

Clinical correlations of steroid receptors and male breast cancer.

Estrogen receptors (ER) were present in tumor specimens from 29 of 34 cases of male breast cancer. There was a significant negative correlation of ER concentration with age. The quantity of ER tended to correlate directly with progesterone receptor levels, disease-free interval, and response duration among responders, but not to a statistically significant extent. In 13 patients for whom response data were available, no significant correlation was observed between ER levels and either frequency or duration of orchiectomy response. Among the six patients with tumor ER levels of less than 30 fmol per mg of protein, however, only two brief responses to orchiectomy occurred that were of little clinical benefit, while three of seven patients with higher ER responded more favorably. Thus, although this suggests that a relationship between low ER and unfavorable orchiectomy response may emerge as more patients are studied, currently available data do not justify basing therapeutic intervention on ER status of a biopsy in a manner analogous to that used for female breast cancer. Nine of 14 male breast cancer patients had positive progesterone receptor assays and several had androgen or glucocorticoid receptors. Tissue from only three of ten men with gynecomastia had measurable ER, and these were limited to the 4S component on sucrose gradients.

Adrenalectomy↗
PubMed1979

Steroid hormone receptors in human colon cancers.

Tumors from patients with primary colon cancer were studied for the presence of steroid hormone receptors for estrogen (E2), progesterone (Prog), dihydrotestosterone (DHT) and glucocorticoid. Ten of 33 (30%) tumors contained high affinity E2 receptors. Four were males and six females with positive assays predominantly from the left colon. Twenty-three of these tumors were also assayed for DHT and Prog and six (26%) contained all three receptors. An additional twelve tumors had at least one receptor, so that 70% of the tumors studied contained one or more receptors. Five of 22 (23%) samples were positive for glucocorticoid receptors. Common etiological factors associated with colon and breast cancer were briefly discussed. These factors, along with the presence of hormone receptors in primary colon malignancies suggest that some large bowel cancers may be endocrine-dependent.

Breast Neoplasms↗
PubMed1979

Estrogen receptor values in patients with benign breast disease.

Tissue specimens from 55 female patients with benign breast disease were assayed for estrogen receptor. Twenty-one of 55 patients (38%) had tumors which contained significant amounts of estrogen receptor (greater than 10 femtomoles/mg protein). Fibroadenomas possessed estrogen receptor more frequently than fibrocystic disease or other benign breast tumors. Estrogen receptor positivity did not correlate with laterality of the tumor; location or size of the largest nodule. Patients with estrogen receptor positive tumors had a mean age of 26.9 years compared to 36.4 years for patients with estrogen receptor negative tumors (p less than 0.01). Twenty of 46 (43%) premenopausal patients had benign tumors which were estrogen receptor positive compared to zero of 8 postmenopausal patients (p less than 0.05).

Adenofibroma↗
PubMed1979

Glucocorticoid receptors and effects in human lymphoid and leukemic cells.

A variety of human leukopathic diseases including human acute lymphoblastic leukemia are responsive to glucocorticoids in a varying proportion of cases. We identified specific glucocorticoid receptors in human acute lymphoblastic leukemia cells. Their presence or absence was well correlated with both in vivo and in vitro responsiveness of these target cells to glucocorticoids. These data suggest that knowledge of glucocorticoid receptor status in human acute lymphoblastic leukemia may aid in selecting patients for therapy. Furthermore, these receptors exhibit significant quantitative differences in various subtypes of human leukemia, with null-cell lymphoblastic leukemia having approximately three times the mean number of receptors per cell as T-cell leukemias. These differences in receptor levels are associated with major differences in complete remission duration independent of other prognosticators of response such as patient age, white count, and cell surface markers. Specific receptors for glucocorticoids can also be identified in normal human peripheral blood monocyte fractions including unpurified peripheral blood lymphocytes, T, and non-T subcomponents of circulating lymphocytes and circulating monocytes. By criteria of quantity, of binding affinity, and specificity, these receptors appear to be similar to other classical glucocorticoid receptors. Receptors in human peripheral blood lymphocytes may be induced threefold on a per cell basis by treatment with the mitogen phytohemagglutinin. This is associated with a marked increase in glucocorticoid responsiveness.

Cytoplasm↗
PubMed1979

Detection of glucocorticoid receptors on Friend erythroleukemia cells.

The inhibition of dimethyl sulfoxide-induced differentiation of Friend erythroleukemia cells by steroids led us to examine these cells for the presence of glucocorticoid receptors. Direct assessement of dexamethasone binding revealed high-affinity dexamethasone receptors on the untreated cells. The specific binding of [3H]dexamethasone was dose dependent. At a concentration of 10(-8) M, almost all binding sites were occupied. The mean number of binding sites per cell in two separate experiments was 8045 and 7191, respectively, and the Kd varied between 3.38 and 3.49 x 10(-9) M. Dimethyl sulfoxide treatment led to a decrease in the number of dexamethasone binding sites on the cells induced to differentiate. After 5 days of treatment, the mean number of sites per cell was reduced to 1216 and 896 in two experiments, with a Kd of 5 x 10(-9) M. Dexamethasone treatment resulted in a moderate decrease in the efficiency of colony formation within 72 hr after the cells were plated in methylcellulose. The mechanism of this inhibitory effect is unknown. However, it was also dose dependent and could be abrogated by appropriate concentrations of progesterone or 11-deoxycortisone. These results suggest that the steroid effects on growth and differentiation of the erythroleukemia cells may be mediated via glucocorticoid receptors.

Animals↗
PubMed1979

Distribution, frequency, and quantitative analysis of estrogen, progesterone, androgen, and glucocorticoid receptors in human breast cancer.

The distribution and frequency of steroid hormone receptors are described 329 patients with breast cancer. The distribution of each of the steroid hormone receptors is unimodal with a progressive increase in the proportion of patients positive at lower receptor values. Receptor values expressed as fmol/mg cytoplasmic protein are well correlated with values expressed as fmol/mg breast tumor. Estrogen receptor was positive in 53% of the patients; progesterone receptor was positive in 38% of the patients; glucocorticoid receptor was positive in 52% of the patients; and androgen receptor was positive in 31% of the patients. The type of tissue assayed did not affect steroid hormone receptor positivity. For primary tumors, there was no correlation between steroid hormone receptor positivity and location of the tumor in the breast, size of the tumor, or extent of the disease. Each of the steroid hormone receptors was positively associated with each of the other steroid hormone receptors. Estrogen receptor was correlated with menopausal status and axillary nodal status, but these correlations did not exist for the other steroid hormone receptors. Estrogen receptor was not correlated with age after adjustment for menopausal status. The other steroid hormone receptors were not correlated with age.

Adult↗
PubMed1979

Chemotherapy for breast cancer.

Chemotherapy employed in the treatment of metastatic breast cancer effectively palliates the disease. Response rates to combination chemotherapy are high (greater than 50%); response durations, however, are still very short (less than 1 year). Future investigations must focus on the development of alternate maintenance regimens to improve response duration. Other areas for future study include the use of immunotherapy in conjunction with chemotherapy and the combination of chemotherapy and endocrine manipulation.

Antineoplastic Agents↗