Prevention of mammary carcinogenesis by short-term estrogen and progestin treatments

INTRODUCTION: Women who have undergone a full-term pregnancy before the age of 20 have one-half the risk of developing breast cancer compared with women who have never gone through a full-term pregnancy. This protective effect is observed universally among women of all ethnic groups. Parity in rats and mice also protects them against chemically induced mammary carcinogenesis. METHODS: Seven-week-old virgin Lewis rats were given N-methyl-N-nitrosourea. Two weeks later the rats were treated with natural or synthetic estrogens and progestins for 7–21 days by subcutaneous implantation of silastic capsules. RESULTS: In our current experiment, we demonstrate that short-term sustained exposure to natural or synthetic estrogens along with progestins is effective in preventing mammary carcinogenesis in rats. Treatment with 30 mg estriol plus 30 mg progesterone for 3 weeks significantly reduced the incidence of mammary cancer. Short-term exposure to ethynyl estradiol plus megesterol acetate or norethindrone was effective in decreasing the incidence of mammary cancers. Tamoxifen plus progesterone treatment for 3 weeks was able to confer only a transient protection from mammary carcinogenesis, while 2-methoxy estradiol plus progesterone was effective in conferring protection against mammary cancers. CONCLUSIONS: The data obtained in the present study demonstrate that, in nulliparous rats, long-term protection against mammary carcinogenesis can be achieved by short-term treatments with natural or synthetic estrogen and progesterone combinations

Transport in disordered interacting systems: Numerical results for one-dimensional spinless electrons

The combined influence of disorder and interactions on the transport properties of electrons in one dimension is investigated. The numerical simulations are carried out by means of the Hartree-Fock-based diagonalization (HFD), a very efficient method to determine the low-energy properties of a disordered many-particle system. We find that the conductance of a strongly localized system can become considerably enhanced by the interactions. The enhancement for long-range interactions is significantly larger than for short-range interactions. In contrast, the conductance of weakly localized systems becomes suppressed by the interactions.Comment: Invited talk presented at Percolation 98, submitted to Physica A, 8 pages, elsart style, 4 eps figures include

Fock space localization, return probability, and conductance of disordered interacting electrons

We numerically simulate the low-energy properties of interacting electrons in a random potential using the Hartree-Fock based exact diagonalization method. In particular, we investigate how the transport properties are influenced by the combined effects of disorder and correlations in the presence of the electron spin. To this end we calculate the participation number of many-particle states in Fock space, the return probability of single-particle excitations, and the Kubo-Greenwood conductance. It turns out that in the strongly localized regime interactions increase the conductance whereas for weak disorder interactions decrease the conductance. In contrast, single-particle excitations in general experience a localizing influence of the interactions.Comment: 4 pages, 4 eps figures, Proc. of the Symposium on Wave Propagation and Electronic Structure in Disordered Systems, FORTH, Heraklion, Crete, Greece (June 2000

Do interactions increase or reduce the conductance of disordered electrons? It depends!

We investigate the influence of electron-electron interactions on the conductance of two-dimensional disordered spinless electrons. By using an efficient numerical method which is based on exact diagonalization in a truncated basis of Hartree-Fock states we are able to determine the exact low-energy properties of comparatively large systems in the diffusive as well as in the localized regimes. We find that weak interactions increase the d.c. conductance in the localized regime while they decrease the d.c. conductance in the diffusive regime. Strong interactions always decrease the conductance. We also study the localization of single-particle excitations close to the Fermi energy which turns out to be only weakly influenced by the interactions.Comment: final version as publsihed, 4 pages REVTEX, 6 EPS figures include

Insulin-like growth factor (IGF)-I obliterates the pregnancy-associated protection against mammary carcinogenesis in rats: evidence that IGF-I enhances cancer progression through estrogen receptor-α activation via the mitogen-activated protein kinase pathway

INTRODUCTION: Pregnancy protects against breast cancer development in humans and rats. Parous rats have persistently reduced circulating levels of growth hormone, which may affect the activity of the growth hormone/insulin-like growth factor (IGF)-I axis. We investigated the effects of IGF-I on parity-associated protection against mammary cancer. METHODS: Three groups of rats were evaluated in the present study: IGF-I-treated parous rats; parous rats that did not receive IGF-I treatment; and age-matched virgin animals, which also did not receive IGF-I treatment. Approximately 60 days after N-methyl-N-nitrosourea injection, IGF-I treatment was discontinued and all of the animal groups were implanted with a silastic capsule containing 17β-estradiol and progesterone. The 17β-estradiol plus progesterone treatment continued for 135 days, after which the animals were killed. RESULTS: IGF-I treatment of parous rats increased mammary tumor incidence to 83%, as compared with 16% in parous rats treated with 17β-estradiol plus progesterone only. Tumor incidence and average number of tumors per animal did not differ between IGF-I-treated parous rats and age-matched virgin rats. At the time of N-methyl-N-nitrosourea exposure, DNA content was lowest but the α-lactalbumin concentration highest in the mammary glands of untreated parous rats in comparison with age-matched virgin and IGF-I-treated parous rats. The protein levels of estrogen receptor-α in the mammary gland was significantly higher in the age-matched virgin animals than in untreated parous and IGF-I-treated parous rats. Phosphorylation (activation) of the extracellular signal-regulated kinase-1/2 (ERK1/2) and expression of the progesterone receptor were both increased in IGF-I-treated parous rats, as compared with those in untreated parous and age-matched virgin rats. Expressions of cyclin D(1 )and transforming growth factor-β(3 )in the mammary gland were lower in the age-matched virgin rats than in the untreated parous and IGF-I-treated parous rats. CONCLUSION: We argue that tumor initiation (transformation and fixation of mutations) may be similar in parous and age-matched virgin animals, suggesting that the main differences in tumor formation lie in differences in tumor progression caused by the altered hormonal environment associated with parity. Furthermore, we provide evidence supporting the notion that tumor growth promotion seen in IGF-I-treated parous rats is caused by activation of estrogen receptor-α via the Raf/Ras/mitogen-activated protein kinase cascade