Estrogens play an important role in regulating the growth and differentiation of normal, premalignant and malignant cell types, especially breast epithelial cells, through interaction with two nuclear estrogen receptors (ER and ERIn this review, we present a brief overview of the actions of estrogens in the different steps of breast carcinogenesis, including cancer progression to metastasis, and of their clinical consequences in the prevention, prognosis and treatment of the disease. The requirement of estrogen receptors, mainly of the alpha subtype, in normal mammary gland differentiation and growth has been evidenced by estrogen receptor deficiency in animals. The promotion of breast cancer carcinogenesis by prolonged exposure to estrogens is well-documented and this has logically led to the use of antiestrogens as potentially chemopreventive agents. In breast cancer progression, however, the exact roles of estrogen receptors have been less well established but they may possibly be dual. Estrogens are mitogenic in ER-positive cells and antiestrogens are an efficient adjuvant therapy for these tumors. On the other hand, the fact that estrogens and their receptors protect against cancer cell invasiveness through distinct mechanisms in experimental models may explain why the presence of ER is associated with well-differentiated and less invasive tumors.2

A B S T R A C T Total and unbound testosterone and A4-androstenedione have been determined in 104 cord blood samples. The same sexual steroids and pituitary gonadotropins have been measured in 46 normal male infants aged 27-348 days and 34 normal female infants aged 19-332 days.In cord blood of female neonates mean total and unbound testosterone was 29.6±7.5 and 0.89±0.4 ng/100 ml, respectively (mean±l SD); A4-androstenedione was 93±38 ng/100 ml. In male neonates mean plasma total and unbound testosterone was 38.9±10.8 and 1.12±0.4 ng/100 ml; A'-androstenedione was 85±27 ng/100 ml.In female infants testosterone concentrations remained constant during the lst yr of life with a mean concentration of 7±3 ng/100 ml. Mean unbound testosterone and A'-androstenedione concentrations were 0.05±0.03 and 16.7±8.3 ng/100 ml, respectively. Mean plasma levels of follicle-stimulating hormone and luteinizing hormone were 8.7±3.3 and 12.9±7.7 mU/ml.In male infants mean plasma total testosterone concentration increased to 208±68 ng/100 ml from birth to 1-3 mo of age, decreasing thereafter to 95±53 ng/100 ml at 3-5 mo, 23.2±18 ng/100 ml at 5-7 mo, and reached prepubertal levels (6.6±4.6 ng/100 ml) at 7-12 mo.Mean unbound testosterone concentration plateaued from birth to 1-3 mo of age (1.3±0.2 ng/100 ml) decreasing to prepubertal values very rapidly. Mean A4-androstene-

During asexual development within erythrocytes, malaria parasites synthesize considerable amounts of membrane. This activity provides an attractive target for chemotherapy because it is absent from mature erythrocytes. We found that compounds that inhibit phosphatidylcholine biosynthesis de novo from choline were potent antimalarial drugs. The lead compound, G25, potently inhibited in vitro growth of the human malaria parasites Plasmodium falciparum and P. vivax and was 1000-fold less toxic to mammalian cell lines. A radioactive derivative specifically accumulated in infected erythrocytes to levels several hundredfold higher than in the surrounding medium, and very low dose G25 therapy completely cured monkeys infected with P. falciparum and P. cynomolgi.

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