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Biomedical subjects

M Lippman

Publications and source records attributed to M Lippman.

At least 55 records · Page 3Linked to original sources
PubMed1983

Cytogenetic studies of human breast cancer lines: MCF-7 and derived variant sublines.

Cytogenetic studies of the human breast cancer cell line MCF-7 and the sublines derived from it demonstrated extensive aneuploidy with both numerical and structural abnormalities and a wide range of heteroploidy. Detailed G-banding analyses showed that loss of marker chromosomes was a rare event, while formation of additional structural abnormalities was very common in these long-term cultures. All chromosomes were involved in these abnormalities. Loss of a morphologically normal X-chromosome may be related to the loss of estrogen receptors in these cell lines. With the exception of one subline, all cell lines had a short homogeneously staining region (HSR) on chromosome 7. Although the parent MCF-7 line had tetrahydrofolate dehydrogenase levels within the normal range, a lengthened HSR has been found in MCF-7 lines that are resistant to methotrexate. This observation strongly favors the association of an increased level of tetrahydrofolate dehydrogenase with HSR. In conclusion, the inherent genetic instability in this group of related cell lines may explain the heterogeneity found in this tumor. Continuous chromosomal rearrangements and numerical changes may reflect an ongoing process of selection and adaptation in these cell lines established from a breast carcinoma and may be characteristic of the aggressiveness of this neoplasm.

Aneuploidy↗
PubMed1982

Decreased nocturnal plasma melatonin peak in patients with estrogen receptor positive breast cancer.

Plasma melatonin concentrations were determined over a period of 24 hours in 20 women with clinical stage I or II breast cancer. In ten of the patients, whose tumors were estrogen receptor positive, the nocturnal increase in plasma melatonin was much lower than that observed in eight control subjects. Women with the lowest peak concentration of melatonin had tumors with the highest concentrations of estrogen receptors. A significant correlation was found between the peak plasma melatonin concentration and the tumor estrogen receptor concentration in 19 of the patients. These data suggest that low nocturnal melatonin concentrations may indicate the presence of estrogen receptor positive breast cancer and could conceivably have etiologic significance.

Adult↗
PubMed1982

Phase II trial of 13-cis-retinoic acid in metastatic breast cancer.

Studies have suggested that both natural and synthetic retinoids have extensive chemopreventive activity against a variety of carcinogens in vivo and in vitro. We have previously shown that growth of human breast cancer cells can be inhibited by retinoids, and retinoic acid-binding proteins have been demonstrated in these cell lines and tumor biopsies. We studied the activity of 13-cis-retinoic acid in the treatment of 18 patients with advanced breast cancer refractory to standard cytotoxic and/or endocrine therapy. Patients began on 0.5 mg/kg and escalated to 8 mg/kg over a one-month period unless toxicity (dry skin, dry mucosa, cheilitis, conjunctivitis) forced dose reduction. All these toxicities responded promptly to dose reduction. Four patients exhibited drug related hypercalcemia, 2 complained of severe earache and several had nausea, vomiting and abdominal cramping. There were no objective responses as defined by standard criteria. One patient with thrombocytopenia secondary to documented marrow involvement demonstrated a recovery of platelet count from 9000 to 110,000. 13-cis-Retinoic acid is not of apparent value in women with heavily pretreated breast cancer.

Breast Neoplasms↗
PubMed1982

Clinical implications of glucocorticoid receptors in human leukemia.

Normal lymphoid cells contain glucocorticoid receptor. A variety of stimuli that activate these cells also induce increases in receptor concentration. Similar glucocorticoid receptors can be detected in lymphoid cells from patients with acute lymphoblastic leukemia (ALL). Absence of the glucocorticoid receptor (usually found in treated patients) predicts lack of glucocorticoid responsiveness. Furthermore, in our hands, glucocorticoid receptor levels correlate with the duration of complete remission in ALL (though not in other forms of leukemia). This association is independent of cell type, age, sex, or initial leukocyte count. The level of receptor shows a negative correlation with increasing aggressiveness of the tumor (null-cell leukemia greater than T-cell leukemia greater than Burkitt's lymphoma).

Acute Disease↗
PubMed1981

The regulation of progesterone receptor by 17 beta estradiol and tamoxifen in the Zr-75-1 human breast cancer cell line in defined medium.

The regulation of progesterone receptor by 17 beta estradiol and tamoxifen in the ZR-75-1 human breast cancer cell line in defined medium is described. ZR-75-1 cells maintained in serum free hormone supplemented medium minus estradiol lack progesterone receptor activity. Readdition of estradiol to these cells leads to a marked stimulation of progesterone receptor activity (0 to greater than 100 fmols of specifically bound progesterone per million cells). Tamoxifen (10(-6)M-10(-8)M) does not stimulate progesterone receptor activity in this cell line. The presence of progesterone receptor activity is not directly related to growth. Withdrawal of insulin in the continued presence of estradiol has no effect on progesterone receptor concentration although net cell growth ceases. Conversely, withdrawal of estradiol in the continued presence of insulin induces a cessation of net cell growth accompanied by a loss of all progesterone receptor activity within 3-5 days.

Breast Neoplasms↗
PubMed1981

The potential for clinical application of in vitro assays predicting 5-FU sensitivity in man.

An in vitro assay system to measure the production of phosphorylated nucleotide products of 5-FU by human tumor cytosols is described. Samples from 11 patients with breast cancer treated with 5-FU-containing chemotherapy regimens were assayed. Significant differences were seen in quantitative and qualitative patterns of phosphorylation between samples from chemotherapy responding and nonresponding patients. Both the rate of 5-fluorodeoxyuridylate production and the amount of fluorinated nucleotide triphosphate produced were significantly increased (P less than 0.05) in patients responding to chemotherapy. The latter finding may be attributed to the demonstration of significantly higher nucleoside diphosphate kinase levels in the tumors of responding patients. Further study of this in vitro assay system as a potential system for prospectively predicting clinical response to fluorinated pyrimidines is indicated.

Breast Neoplasms↗
PubMed1981

Melatonin inhibition and pinealectomy enhancement of 7,12-dimethylbenz(a)anthracene-induced mammary tumors in the rat.

The effects of the pineal hormone, melatonin, and of pinealectomy on the incidence of mammary adenocarcinoma in Sprague-Dawley rats treated with 7,12-dimethylbenz(alpha)-anthracene (DMBA) were investigated. Melatonin (2.5 mg/kg), begun on the same day as DMBA (5 mg) treatment and given daily in the afternoon for 90 days, significantly reduced the incidence of mammary tumors from 79% (control) to 20% (treated) (p less than 0.002). Rats pinealectomized at 20 days of age and treated with 7 mg of DMBA at 50 days of age had a higher incidence of tumors (88%) compared to control animals (22%). Fifteen mg of DMBA, which resulted in a higher incidence of tumors, reduced the difference between pinealectomized and control animals. Melatonin only partially reversed the effects of pinealectomy, reducing the incidence from 87% (pinealectomy alone) to 63% (pinealectomy plus melatonin); however, the tumor incidence was still lower (27%) in nonpinealectomized, melatonin-treated animals. Assessment of plasma prolactin, luteinizing hormone, follicle-stimulating hormone, estradiol, and cortisol in DMBA-treated tumor-free and tumor-bearing animals revealed a significantly lower plasma prolactin concentration [27 +/- 5 (S.E.) ng/ml] in melatonin-treated animals as compared to vehicle-treated animals [65 +/- 8 ng/ml]. The concentration of plasma prolactin was less in melatonin-treated, pinealectomized rats (55 +/- 10 ng/ml) as compared to vehicle-treated, pinealectomized animals (101 +/- 13 ng/ml). Other hormones were not affected by melatonin treatment. These data support the hypothesis that melatonin inhibits the development of DMBA-induced mammary tumors in the rat while removal of the pineal gland stimulates development of such tumors. Additionally, these experiments provide evidence that these effects may be mediated by a suppression of plasma prolactin levels.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1980

Prediction of clinical response to 5-fluorouracil-containing chemotherapy: preliminary results of in vitro assay in human breast cancer.

An in vitro assay system measuring the production of phosphorylated nucleotide products of 5-FU by human tumor cytosols is described. Samples from 11 patients with breast cancer treated with 5-FU-containing chemotherapy regimens were assayed. Significant differences were seen in quantitative and qualitative patterns of phosphorylation between samples from chemotherapy responding and nonresponding patients. The rate of 5-fluorodeoxyuridylate production and the amount of nucleotide triphosphate produced were significantly P < 0.05 increased in chemotherapy-responding patients. This in vitro assay system is a simple, reproducible procedure that requires further evaluation as a potential system for prospectively predicting clinical response to fluorinated pyrimidines.

Breast Neoplasms↗
PubMed1980

Purification of estrogen receptors from MCF-7 human breast cancer cells.

We have partially purified human estrogen receptor from MCF-7 breast cancer cells in order to further characterize the chemical and biological properties of the receptor and to prepare specific receptor antibodies for radioimmunoassay. The estrogen receptor from MCF-7 cell cytosol was purified 1,166-fold (27% recovery) over starting cytosol by combining ammonium sulfate precipitation, affinity chromatography, and Sephadex G-100 gel filtration. The affinity resin consisted of estrone 17-(O-carboxymethyl)oxime:bovine serum albumin: Sepharose 4B. Under high salt conditions, the molecular weight of the purified receptor is 50,000 and is identical to that obtained on chromatography of crude cytosol. Sucrose density gradient centrifugation also revealed the purified receptor sedimenting at the same position as the crude cytosol receptor. The following methods to purify crude cytosol estrogen receptors are much less effective. (a) With DNA-cellulose chromatography, KCl elution revealed peaks at 0.04 M KCl (11-fold purification) and 0.22 M KCl (12.5-fold purification). This could not be combined sequentially with affinity chromatography because high salt conditions were required for affinity elution, and removal of salt by dialysis caused the receptor to adhere to the tubing. (b) With hydroxylapatite chromatography, phosphate elution revealed peaks at 0.12 M phosphate (1.1-fold purification) and 0.175 M phosphate (1.1-fold purification). (c) With phosphocellulose chromatography, KCl elution revealed only one peak at 0.18 M KCl (1.6-fold purification). (d) With diethylaminoethyl cellulose chromatography, KCl elution revealed 4 peaks at 0.025 M (1-fold purification), 0.12 M (1.27-fold purification), 0.14 M (1.28-fold purification), and 0.2 M (0.36-fold purification).

Breast Neoplasms↗
PubMed1978

Role of pineal gland in aetiology and treatment of breast cancer.

The hypothesis that diminished function of the pineal gland may promote the development of breast cancer in human beings is suggested by the relation between breast cancer and prolonged oestrogen excess, and by the observation that the pineal secretion, melatonin, inhibits ovarian oestrogen production, pituitary gonadotrophin production, and sexual development and maturation. The hypothesis is supported by the following points. (1) Pineal calcification is commonest in countries with high rates of breast cancer and lowest in areas with a low incidence; the incidences of pineal calcification and of breast cancer are moderate among the black population in the United States. (2) Chlorpromazine raises serum-melatonin; there are reports that psychiatric patients taking chlorpromazine have a lower incidence of breast cancer. (3) Although information is lacking on breast cancer, the pineal and melatonin may influence tumour induction and growth in experimental animals. (4) The demonstration of a melatonin receptor in human ovary suggests a direct influence of this hormone on the ovarian function, and possibly oestrogen production. (5) Impaired pineal secretion is believed to be an important factor triggering puberty (early menarche is a risk factor for breast cancer).

Breast Neoplasms↗