Biomedical subjects

R E Hall

Publications and source records attributed to R E Hall.

At least 55 records · Page 3Linked to original sources

PubMed1990

Steroid hormone receptor gene expression in human breast cancer cells: inverse relationship between oestrogen and glucocorticoid receptor messenger RNA levels.

The relative expression in human breast cancer cells of messenger ribonucleic acids (mRNA) encoding different steroid hormone receptors is unknown. Accordingly, mRNA levels in total RNA extracted from 13 human breast cancer cell lines were measured by Northern analysis employing complementary DNA probes for the human oestrogen (ER), progesterone (PR), androgen (AR), vitamin D3 (VDR) and glucocorticoid receptors (GR). The 7 ER+ lines expressed a single 6.4 kilobases (kb) ER mRNA. Interestingly, low concentrations of ER mRNA were detected in the ER- cell lines, MDA-MB-330 and BT 20. PR mRNA, predominantly a 13.5 kb species, was expressed in the 6 lines known to be ER+, PR+ by radioligand binding; however, one ER+ cell line, MDA-MB-134, failed to express PR mRNA. A 10.5 kb AR mRNA was expressed at significantly higher levels in ER+ than ER- cell lines. All cell lines expressed a single 4.6 kb mRNA for VDR and a single 7.4 kb mRNA for GR. ER and PR mRNA levels were positively correlated (p = 0.011) and each was positively correlated with androgen receptor (AR) mRNA levels (p less than or equal to 0.009). ER, PR and AR mRNAs were negatively associated with GR levels (p less than or equal to 0.012), while ER and AR mRNA levels were negatively correlated with mRNA for the epidermal growth factor receptor. In contrast, levels of VDR mRNA were unrelated to the concentration of any other steroid receptor mRNA. Our data demonstrate the coordinate expression of ER, PR and AR genes, and an inverse relationship between sex steroid hormone receptor and GR gene expression in human breast cancer cell lines.

Blotting, Northern↗

PubMed1990

Respiratory chain-linked NADH dehydrogenase. Mechanisms of assembly.

The assembly of mitochondrially and cytoplasmically translated subunits of NADH dehydrogenase in the inner mitochondrial membrane was studied in rat hepatoma cultures. A polyclonal antibody to the purified bovine heart holoenzyme, which reacted with comigrating proteins of both rat liver and hepatoma mitochondria on immunoblots, precipitated 25-30 [35S]methionine-labeled proteins from hepatoma cell lysates. Six of these were sensitive to an inhibitor of mitochondrial translation (chloramphenicol), resistant to an inhibitor of cytosolic translation (cycloheximide), and were not present in cytochrome oxidase. By these criteria, six NADH dehydrogenase subunits are identified as being translated on mitochondrial ribosomes. The metabolic properties of the three most prominent of these at 51, 43, and 11 kDa were studied in more detail. Mitochondrial and nuclear-coded polypeptides assemble into NADH dehydrogenase at different rates as measured by incorporation of pulse-labeled proteins into immunoprecipitable enzyme. Nuclear-coded, imported polypeptides appear immediately after a pulse with [35S]methionine and retain constant stoichiometry. Mitochondrially coded proteins, although rapidly translated, appear at peak levels at different times between 0 and 12 h of chase in the immunoprecipitated enzyme. Ongoing synthesis and import of nuclear-coded proteins is necessary for mitochondrially coded proteins to be assembled. Excess, unassembled mitochondrially translated subunits are degraded in an oligomycin-sensitive manner. These data are consistent with a model in which a scaffold of imported proteins forms the inner core of the enzyme, and later arriving mitochondrially translated proteins attach to the scaffold in a time-dependent manner.

Animals↗

PubMed1990

Role of CD18 in lymphokine activated killer (LAK) cell-mediated lysis of human monocytes: comparison with other LAK targets.

The role of CD18, identified as the beta chain of the CD11 family of adhesion glycoproteins, in the lysis of normal autologous monocytes by interleukin-2-activated killer (LAK) cells was explored. The addition of several preparations of anti-CD18 monoclonal antibodies (MAbs) to the incubation mixture of LAK cells and various target cells indicated that lysis of autologous monocytes, K562 erythroleukemia tumor cells, FMEX melanoma tumor cells, and fresh ovarian tumor cells were readily inhibited by all anti-CD18 antibodies tested. Kinetic experiments demonstrated that significant inhibition of lysis occurred if RH1-38 antibody was added up to 2 hr after LAK cells were added to target cells. By the use of selective coating of targets and effector cells with RH1-38, it was determined that anti-CD18 antibody inhibited lysis at the effector cell level but not at the target cell level, although CD18 was detectable on the surface of monocyte targets by FACS analysis and immunoprecipitation. Furthermore, specific binding of LAK cells to all targets tested was not affected by the presence of anti-CD18, indicating that lysis of target cells was blocked at a post-binding event. Finally, of the 3 alpha chains associated with CD18, only antibodies to LFA-1 (CD11a) partially blocked binding of LAK cells to monocytes and tumor cells. It is possible, then, that both CD11a and CD18 may work in concert to effect the lysis of target cells by LAK cells.

Antigens, CD↗

PubMed1990

Initial characterization of a cytokine which induces differentiation and cytolytic activity in HL-60 promyelocytic leukemia cells: evidence that the cytokine is distinct from other known differentiation-active cytokines.

In this paper we report that, like dimethyl sulfoxide (DMSO), retinoic acid (RA), and conditioned medium (CM) from lectin-stimulated mononuclear leukocytes, CM from a human null cell leukemia line (Reh) induces HL-60 promyelocytic leukemia cells to respond in an enhanced manner to phorbol diester (PDE). Furthermore, Reh-CM induces PDE-resistant HL-60-1E3 cells to respond to PDE and lyse target cells. Additionally, both HL-60 and HL-60-1E3 cells exposed to Reh-CM for 3 days produce superoxide anion and express cell surface antigens present on mature mononuclear phagocytes. No colony-stimulating factor (CSF) or interferon (IFN) activity was detected in Reh-CM, and differentiation activity (DA) was not removed from Reh-CM by insolubilized anti-IFN gamma. While Reh-CM is antiproliferative against a panel of cell lines, its spectrum of activity is different than tumor necrosis factor (TNF) alpha, and neither TNF alpha nor TNF beta inhibit proliferation of HL-60-1E3 or induce these cells to respond to PDE. The differentiation factor (DF) material has been partially purified by ammonium sulfate precipitation and is non-dialyzable; unstable to heat, acid, or alkali treatment; and the activity is not blocked by anti-IL-6 or anti-IFN alpha. The data presented in this paper suggest the presence of a differentiation-inducing factor which is distinct from CSF, IFN alpha or -gamma, TNF alpha, or -beta, or IL-6, which may play a role in the differentiation of malignant (leukemic) and normal cells of the myelomonocytic lineage.

Biological Factors↗

PubMed1990

Inverse relationship between estrogen receptor and epidermal growth factor receptor mRNA levels in human breast cancer cell lines.

Epidermal growth factor receptors (EGF-R) are present in a number of human breast cancer cell lines and tumor biopsies. Furthermore, it has been suggested that EGF-R levels are higher in estrogen receptor negative (ER-) than in ER+ human breast tumors and that EGF-R status may be a prognostic indicator in breast cancer. The present study was undertaken to establish whether there is a quantitative relationship between EGF-R and ER mRNA concentrations in a series of 10 well-characterized human breast cancer cell lines. All cell lines expressed detectable quantities of EGF-R mRNA by Northern analysis but the relative abundance of EGF-R mRNA varied more than 50-fold. Two transcripts corresponding to the 10.5- and 5.8-kb mRNAs described in other cell types were present but in different relative proportions in different cell lines. When these lines were divided into an ER+ and an ER- group based on their ability to bind estradiol, ER- cell lines were shown to express significantly higher concentrations of EGF-R mRNA than did ER+ cell lines (p less than 0.005). Furthermore, linear-regression analysis revealed a significant inverse relationship between ER and EGF-R mRNA concentrations both within the group of 10 human breast cancer cell lines as a whole (r = 0.66) and within the 6 functionally ER + lines (r = 0.77). This demonstration of a significant (p less than 0.005) inverse relationship between the concentrations of ER and EGF-R mRNAs in ER + cell lines raises the possibility of reciprocal regulation of the expression of these genes in human breast cancer.

Blotting, Northern↗

PubMed1989

P48 induces tumor necrosis factor and IL-1 secretion by human monocytes.

Bacterial products are potent stimulators of TNF and IL-1 release, however, the factors that regulate cytokine secretion in the absence of bacterial products are not well defined. P48 is a cytokine recently identified in the supernatant of the human null cell leukemia cell line Reh, which induces differentiation and cytolytic activity in HL-60 cells. P48 has been purified to homogeneity and is distinct from TNF-alpha TNF-beta, IFN-gamma, IL-6, and macrophage CSF. In the present study we examined the ability of P48 to stimulate cytokine release by human peripheral blood monocytes. P48 stimulated the secretion of TNF and IL-1 in a dose-dependent manner. Priming the monocytes with IFN-gamma enhanced P48-induced cytokine release but was not a requirement for secretion. Cytokine secretion was in response to P48 and was not caused by endotoxin contamination. The cytokine-inducing activity of P48 was extremely sensitive to heat treatment but could not be eliminated by using polymyxin B. Polyclonal antisera to P48 completely blocked the cytokine-inducing activity. P48 may be an important new member of the cytokine network involved in the regulation of cytokine secretion by monocytes.

Animals↗

PubMed1989

Characterization of a K562 multidrug-resistant cell line.

A daunorubicin-resistant variant of the K562 human leukemia cell line (K562-R), which demonstrates cross-resistance to other anthracycline antibiotics and Vinca alkaloids, has been developed in vitro by continuous exposure to daunorubicin. Cross-resistance to anthracyclines and Vinca alkaloids is reversed when cells are exposed to drugs in the presence of verapamil, a calcium channel blocker. The K562-R cell line overexpresses a 4.5-kilobase mRNA, which is thought to code for the Mr 170,000 membrane glycoprotein associated with multidrug resistance. Transport studies indicate reduced intracellular accumulation and retention of daunorubicin in the K562-R cells as compared to the parent cell line. These studies further suggest the presence of distinct cellular pools composed of both rapidly and slowly exchanging drug, with the rapidly exchanging pool being more pronounced in the resistant line. The development of multidrug resistance in the K562-R cell line is also associated with the overexpression of five different cell surface membrane proteins ranging in molecular weight between 50,000 and 210,000, whose function remains to be defined.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1989

Purification and further characterization of a non-tumor necrosis factor alpha or beta differentiation-inducing cytokine, P48.

In this report, we present the further characterization and purification of a cytokine differentiation factor, termed P48, which unlike previously described differentiation factors is antigenically unrelated to tumor necrosis factor alpha (TNF-alpha), tumor necrosis factor beta (TNF-beta), and gamma interferon. HL-60 cells and phorbol diester-resistant HL-60-1E3 cells exposed to conditioned medium from Reh cells mature along the monocyte/macrophage pathway, as assessed by several assays (express nonspecific esterase, produce superoxide anion, morphologically resemble monocytes, mediate phorbol diester-triggered extracellular cytolytic activity). Reh cell conditioned medium is antiproliferative toward a panel of cell lines, is not nonspecifically cytotoxic, has no antiviral or colony-stimulating factor activities, and is not affected by exposure to insolubilized anti-gamma interferon. A 48-kDa glycoprotein (P48) which mediates this differentiation factor activity has been purified to homogeneity from Reh cell conditioned medium, and a polyclonal neutralizing antiserum has been produced. P48 activity is not blocked by either anti-TNF-alpha and anti-TNF-beta and on Western blot analysis is antigenically distinct from TNF-alpha and TNF-beta. In addition, polyclonal anti-P48 does not block either TNF-alpha or TNF-beta activities or recognize either on Western blots. Unlike gamma interferon, colony-stimulating factor, TNF-alpha, or TNF-beta, P48 reverses phorbol diester resistance of HL-60-1E3 cells. These studies present strong evidence for the existence of a previously unrecognized cytokine which, unlike other reported differentiation factors, is antigenically unrelated to TNF-alpha or TNF-beta. P48 may play an important role in growth and development of normal and abnormal (leukemic) hematopoietic and nonhematopoietic cells.

Animals↗

PubMed1989

A one-step, low background coomassie staining procedure for polyacrylamide gels.

Present Coomassie staining procedures require hours of destaining and/or have high backgrounds. This one-step staining procedure is easier, gives lower background with no loss in sensitivity, uses less chemicals, requires less time, and can be followed by silver stain if increased sensitivity is desired after analyzing the results.

Acrylic Resins↗

PubMed1989

Bilateral hyperplasia of the mandibular coronoid processes: a report of two cases.

Two cases of bilateral coronoid hyperplasia of the mandible are presented. Consistent with other reported cases, the patients were men whose onset of symptoms correlated with the onset of puberty. One case was unusual in that bilateral coronoidectomies did not relieve the restriction of mandibular movement. Additional masseter muscle and fascial surgery was required to provide unrestricted mandibular motion.

Adult↗

PubMed1989

The application of panoramic zonography to the diagnosis of maxillofacial fractures.

Traditionally, multiple radiographic views and techniques were required to elucidate the nature and extent of fractures of the maxillofacial complex. As a result, patient cost in terms of time, expense, manipulation, and radiation exposure scaled upward. Synthesis and interpretation of the fragmented bits of information from multiple films also constituted a labor-intensive process. A new imaging modality, panoramic zonography, provides precise anatomic imaging of preselected areas of interest with minimal radiation exposure. The usefulness of this technique in the diagnosis, treatment, and follow-up of traumatic events in the mandibular and maxillofacial regions is illustrated by a series of cases.

Adult↗

PubMed1989

Interleukin-2 modulates the expression of lymphocyte function-associated antigen-one (LFA-1) and p150,95 during the generation of lymphokine-activated killer (LAK) cells.

Lymphocyte function-associated antigen-one (LFA-1), Mac1 and p150,95 represent a family of heterodimeric cell surface molecules with a common beta subunit and distinct alpha subunits. LFA-1 is known to be functionally important in cell-cell interactions between immune cells. In the present study, a mouse monoclonal antibody (mAb), RH1-38, which recognizes an epitope on the beta-chain of LFA-1 was used to study the function and expression of LFA-1 on lymphokine-activated killer (LAK) cells. This mAb has been shown previously to block, in the absence of complement, cytolytic activity mediated by natural killer (NK) cells, cytotoxic T lymphocytes (CTL), and a monocyte-like cell (phorbol diester-stimulated HL-60 cells). LAK cells were generated by culturing in vitro human peripheral blood lymphocytes (PBL) in the presence of human recombinant interleukin-2 (rIL-2), and cytotoxic activity was measured by a 51Cr-release assay using the human NK-resistant Daudi cell line. Addition of RH1-38 ascites supernatant, purified RH1-38 mAb, or F(ab')2 fragment of RH1-38 markedly reduced (>80) LAK cytolytic activity, whereas NS-1 (parent hybridoma) ascites supernatant, normal mouse IgG, and monoclonal anti-HLA had no effect on LAK-mediated killing. Equivalent inhibition of NK and CTL activity by purified RH1-38 required 10-100-fold more antibody. Appreciable inhibition occurred if the mAb was added up to 2 hr after LAK cells were mixed with targets. Indirect immunofluorescence flow cytometry and immunoprecipitation studies revealed that LFA-1 and p150,95 expression were dramatically enhanced in PBL populations cultured with rIL-2 compared with PBL cultured without rIL-2; Daudi cells expressed no detectable LFA-1 family heterodimers. Time-course experiments demonstrated that during culture of PBL in the presence of rIL-2, development of enhanced expression of LFA-1 and p150,95 correlated closely with LAK cytolytic activity. These studies (i) demonstrate that LFA-1 and/or p150,95 are functionally important effector cell surface molecules expressed by LAK cells and that some homology to NK and CTL mechanisms of cell-mediated lysis may exist; and (ii) suggest that enhanced LFA-1 and/or p150,95 expression are important for development of the fully differentiated LAK effector cell in the presence of rIL-2.

Antibodies, Monoclonal↗

PubMed1988

Effect of medroxyprogesterone acetate on proliferation and cell cycle kinetics of human mammary carcinoma cells.

The effect of medroxyprogesterone acetate (MPA) on breast cancer cell proliferation kinetics was investigated in ten human breast cell lines growing as monolayer cultures. Significant inhibition of growth occurred only in the estrogen receptor-positive, progesterone receptor-positive cell lines, T-47D, MCF-7, ZR 75-1, BT 474, and MDA-MB-361. Among these cell lines sensitivity to MPA varied widely; concentrations required for 20% inhibition of growth ranged from 0.04 nM for T-47D to greater than 100 nM for ZR 75-1 cells. Furthermore, although the most sensitive line, T-47D, had the highest level of PR, sensitivity to MPA was not correlated with PR levels among the responsive cell lines. More detailed studies were undertaken with the T-47D cell line. The growth-inhibitory response was confined to the progestins: MPA, ORG 2058, R5020, and progesterone, while androgens, estrogens, and glucocorticoids were without effect over the same concentration range (0.1-100 nM). MPA-induced growth inhibition was associated with a significant decrease in the proportion of S-phase cells with an accumulation of cells in the G0-G1 phase of the cell cycle. Cells began to accumulate in G0-G1 after 12 h of drug treatment and the effect was maximal by 24 h, i.e., maximal effects were observed during the first cell cycle following drug treatment. By contrast, significant accumulation in G0-G1 required exposure of MCF-7 cells to MPA for at least two cell cycle times, i.e., 48 h and the effect was still increasing at 96 h. Stathmokinetic studies revealed that in both cell lines accumulation in the G0-G1 phase was due to an MPA-induced increase in the G1 transit time. These data indicate that MPA and other progestins have direct growth inhibitory effects on estrogen receptor-positive and progesterone receptor-positive human breast cancer cells in vitro and these effects can be accounted for by a decrease in the rate at which cells traverse the G1 phase of the cell cycle.

Breast Neoplasms↗

PubMed1988

Hibernoma: an unusual tumor of adipose tissue.

A case of a benign tumor of vestigial brown fat (hibernoma) is presented. The circumstances surrounding an associated odontogenic infection are discussed. The case and a review of the literature are presented to clarify a pathologic condition rarely included in the differential diagnosis of head and neck masses.

Adipose Tissue, Brown↗

PubMed1988

In vitro effects of low intensity direct current generated silver on eukaryotic cells.

An examination of the effects of low intensity direct current generated silver, (LIDC Ag) on several types of eukaryotic microorganisms and cell culture lines suggests that LIDC Ag has an appropriate selective toxicity for prokaryotic cells. It appears that levels of this agent could be obtained clinically that would have marked bacteriostatic activity and yet have little or no effect on mammalian cells.

Animals↗

PubMed1987

Altered regulation of c-myc in an HL-60 differentiation resistant subclone, HL-60-1E3.

HL-60 cells treated with phorbol dibutyrate (PDBu) differentiate into cells which functionally and morphologically resemble macrophages (G. Rovera, D. Santoli, and D. Damskey, Proc. Natl. Acad. Sci. USA, 75: 2779-2783, 1979; E. Huberman and M.F. Callahan, Proc. Natl. Acad. Sci. USA, 76:1293-1298, 1979). This differentiation involves modulation of the expression of several cellular oncogenes. However, the significance of the temporal relationships between differentiation events and specific oncogene expression are not known. Others have reported that transcriptional down regulation of c-myc occurs early in the differentiation of HL-60 cells (R.D. Dalla-Favera et al., Haematol. Blood Transfusion, 28: 247-253, 1983; L.E. Grosso and H.C. Pitot, Biochem. Biophys. Res. Commun., 119: 473-480, 1984). To determine the significance of the regulation of c-myc during HL-60 maturation, we performed parallel PDBu induction studies analyzing the kinetics of expression of c-myc, cell cycle frequency distribution, cytotoxic effector activity, and clonogenic potential in HL-60 cells and in a partial-differentiation resistant HL-60 clone (HL-60-1E3) (J. A. Leftwich, P. Carlson, B. Adelman, and R. E. Hall, Cancer Res., 47: 1319-1324, 1987). We report that PDBu stimulation results in early c-myc transcriptional down regulation in the HL-60-1E3 clone cells with the same kinetics as has been previously reported for HL-60 parental cells (R. D. Dalla-Favera et al., Haematol. Blood Transfusion, 28: 247-253, 1983; L. E. Grosso and H. C. Pitot, Biochem. Biophys. Res. Commun., 119: 473-480, 1984). However, reexpression of c-myc occurs 15 hours postinduction in HL-60-1E3 but not parental cells. This reexpression is maintained through 30 h of stimulation and correlates with a lack of terminal commitment as assessed by an increase in clonogenic potential and the inability of these cells to acquire cytotoxic function. Sequential stimulation of HL-60-1E3 cells with DMSO and PDBu overcomes the block in macrophage differentiation (J. A. Leftwich, P. Carlson, B. Adelman, and R. E. Hall, Cancer Res., 47; 1319-1324, 1987). Such treatment results in a transient reexpression of c-myc at 15 h after PDBu treatment, and the complete downregulation of c-myc 24 h postinduction. These data suggest that the reported early decrease in c-myc transcripts following PDBu stimulus in HL-60 cells is not sufficient to commit these cells to macrophage-like terminal differentiation. Late regulation of c-myc gene expression may be an important additional component of the regulatory mechanisms which allow HL-60 cells to complete this program.

Cell Cycle↗

PubMed1987

HL-60-1E3, a novel phorbol diester-resistant HL-60 cell line.

The HL-60 (human promyelocytic leukemia) cell line has proved to be a useful model for the study of the expression of cellular functions and markers associated with hematopoietic differentiation. We report here the development and initial characterization of a novel, differentiation-resistant HL-60 cell line (HL-60-1E3) which was established by cloning the parent HL-60 line in the absence of mutagens or differentiation-inducing agents. HL-60-1E3 exhibits markedly reduced phorbol diester-induced expression of extracellular cytolytic activity, nonspecific esterase, phagocytosis, and surface Mo1 antigen. In addition, dimethyl sulfoxide-induced expression of both Mo1 and Mo2 is markedly reduced. However, if HL-60-1E3 is exposed to dimethyl sulfoxide, it acquires appreciable phorbol diester-triggered cytolytic activity and production of superoxide anion (O2-). Phorbol diester receptor number and dissociation constant (Kd) obtained by Scatchard analysis are not significantly different for the two cell lines. The HL-60-1E3 cell line should provide a useful adjunct to other cell lines used in the study of normal myeloid and leukemic cell differentiation, as well as the study of cytokine maturation factors and oncogene expression.

Antibodies, Monoclonal↗

PubMed1987

Mechanisms of growth inhibition by nonsteroidal antioestrogens in human breast cancer cells.

Treatment of MCF7 human mammary carcinoma cells with the nonsteroidal antioestrogens, tamoxifen and clomiphene, leads to a concentration-dependent decrease in cellular proliferation rate which can be resolved into oestrogen-reversible and oestrogen-irreversible components. This became more clearly apparent when cells were treated with the 4-hydroxylated derivatives of these compounds where, because of enhanced affinity for the oestrogen receptor (ER), the dose-response curves for the two components could be separated. Thus treatment with 4-hydroxyclomiphene resulted in a distinct biphasic effect on cell growth. In the concentration range 10(-10)-10(-8) M, cell proliferation was inhibited in a concentration-dependent manner to a maximum of 60-70%, there was no further effect between 10(-8) and 10(-6) M, but at concentrations greater than 10(-6) M there was another concentration-dependent decrease in cell growth. Studies with a series of vinyl-substituted hydroxytriphenylethylenes revealed that in the nanomolar concentration range, where the effects of the drugs could be completely negated by the simultaneous addition of oestradiol, the potency for growth inhibition was highly correlated with affinity for ER. Such data provide strong evidence that in this concentration range the growth inhibitory effects of nonsteroidal antioestrogens are mediated by the intracellular ER. In the micromolar concentration range the effects of antioestrogens are not completely reversed by oestradiol, potency is not well correlated with affinity for either ER or the antioestrogen binding site (AEBS) but the effect is cell cycle phase-specific. Furthermore, the disparity between the affinity for AEBS (0.8-3.3 nM) and the concentration of drug needed for oestrogen-irreversible growth inhibition (greater than or equal to 2.5 microM) argue against a central role for AEBS in mediating this effect. The observation that triphenylethylene antioestrogens are calmodulin antagonists may provide some insight into potential mechanisms for this oestrogen-irreversible effect. Indeed, in identical experiments two phenothiazine calmodulin antagonists inhibited MCF 7 cell proliferation at concentrations greater than or equal to 2.5 x 10(-6) M. Growth inhibition following administration of fluphenazine, perphenazine and triphenylethylene antioestrogens was accompanied by qualitatively similar changes in the cell cycle kinetic parameters, i.e. accumulation in G1 phase at the expense of S phase cells. These data suggest triphenylethylene antagonism of calmodulin activated cellular processes as a potential mechanism for the oestrogen-irreversible effects of the nonsteroidal antioestrogens.

Breast Neoplasms↗