Biomedical subjects

E M Cormier

Publications and source records attributed to E M Cormier.

4 recordsLinked to original sources

PubMed1996

Determination of the intra- and interlaboratory reproducibility of the low volume eye test and its statistical relationship to the Draize eye test.

The reproducibility of toxicologic test methods, including alternative tests, is a key scientific and regulatory concern. In the present work, historic rabbit eye irritation data were used to determine the intra- and interlaboratory reproducibility of the low volume eye test (LVET). The standard Draize eye irritation test was used as the basis for comparison. The LVET and Draize tests had similar degrees of intra- and interlaboratory reproducibility as determined by examination of their coefficients of variation, although the variability in LVET results was directionally lower. Results from 70 parallel Draize and LVET tests indicated a strong positive association between results from the two tests, for corneal, iridial, conjunctival, and maximum average scores (MAS). Correlation coefficients were 0.60, 0.73, 0.69, and 0.73, respectively (P </= 0.0001). The linear relationship between LVET and Draize MAS values was examined by regression analysis and found to follow the relationship LVET MAS = 0.522 (Draize MAS). Thus, the LVET is at least as reproducible as the Draize test and gives responses that are (linearly) correlated to the Draize. The previous findings that the LVET is more predictive of human eye responses than the Draize test lends additional support for its use as a refined alternative to the Draize test.

Alcohols↗

PubMed1989

Decrease in estradiol-stimulated progesterone receptor production in MCF-7 cells by epidermal growth factor and possible clinical implication for paracrine-regulated breast cancer growth.

These studies have evaluated the modulation by epidermal growth factor (EGF) of estrogen receptor (ER) levels and estradiol-stimulated progesterone receptor (PgR) synthesis. Short-term culture of MCF-7 cells in an "estrogen (phenol red indicator)-free" environment caused a rise in ER concentration that is inhibited by EGF at 10(-8) M and 10(-7) M. Estradiol at 10(-10) M induced a 5-fold increase of PgR over a 5-day assay period. However, the rise in PgR was diminished or prevented by increasing concentrations of EGF (10(-9) M to 10(-7) M). Similarly, the concentration-related rise in PgR caused by estradiol (10(-13) M to 10(-9) M) was abolished after a 7-day pretreatment with EGF (10(-7) M). For both the ER and PgR receptor, EGF treatment caused a decrease in receptor number without an apparent change in receptor affinity. Thus, EGF appears to down regulate the ER by approximately 50% and to diminish the ability of estradiol to induce PgR. In addition, a survey of ER+PgR+ and ER+PgR- values of primary breast tumors from women between the ages of 55 and 70 demonstrated significantly less (50%) (85 to 39 fmol/mg of cytosol protein) ER in ER+PgR- tumors (P = 0.0005). The median PgR values for the PgR-positive tumors were 139 fmol/mg of cytosol protein. We propose that ER+ breast cancer that has changed to a paracrine growth factor-driven system (from stromal cells or ER- breast cancer cells) is less responsive to gonadal steroids. The loss of PgR in these ER+ carcinomas may be an indicator of this type of hormone independence.

Breast Neoplasms↗

PubMed1989

Contrasting ability of antiestrogens to inhibit MCF-7 growth stimulated by estradiol or epidermal growth factor.

A potential mechanism is described by which a growth factor may prevent the action of antiestrogens or reactive the growth of hormone-responsive breast carcinoma in patients undergoing tamoxifen (TAM) treatment. Epidermal growth factor (EGF)-stimulated growth (10(-8) M EGF) was assayed in the MCF-7 breast cancer cell line in the presence of various concentrations (10(-10) to 10(-6) M) of three antiestrogens, 4-hydroxytamoxifen (OH TAM), TAM and ICI 164384. In each case, the EGF-stimulated increases in DNA were not inhibited by the antiestrogen. OH TAM and ICI 164384 inhibited estradiol (E2) stimulated cell proliferation in a dose-related fashion. However, in the presence of both E2 and EGF, these two antiestrogens inhibited E2 effects only; EGF promotion of growth was unaffected. Pretreatment of MCF-7 cells for 2 days with either OH TAM or ICI 164384 did not inhibit EGF-induced increases in cell proliferation. We propose that eventual antiestrogen therapeutic failure may be caused by the paracrine influences of growth factors from neighboring cells.

Breast Neoplasms↗

PubMed1988

Estrogen receptor distribution in enucleated breast cancer cell lines.

The intracellular location of estrogen receptors in hormone-responsive cells has been studied with a number of techniques which indicate that the unoccupied receptors are nuclear and not cytoplasmic proteins. We used cell enucleation of two human breast cancer-derived cell lines, MCF-7 and T47D, to determine whether the unoccupied receptors were also nuclear in these cells and to determine whether the weak estrogen phenol red, present in nearly all tissue culture media, affected the distribution of the receptors seen with this technique. Nucleoplasts prepared from the breast cancer cells contained most of the estrogen receptors that were present in whole cells. The cytoplast fraction, which contained some contaminating whole cells, also contained some receptors. However, incubating cells with estradiol before enucleation did not translocate any receptors out of the cytoplast fraction (to the nucleoplasts). The unoccupied receptors appeared to be almost exclusively nuclear in these cells. The same results were obtained with either radioligand binding or enzyme-linked immunoassay used to measure estrogen receptor, and the distribution of receptors was unaffected by the presence of the pH indicator phenol red. In addition, we observed changes in the estrogen receptor content of incubated cytoplasts that were consistent with receptor synthesis, and this may prove to be a useful model system to characterize receptor synthesis and degradation.

Breast Neoplasms↗