Melatonin and estrogen in breast cyst fluids.

Increased breast cancer risks have been reported among women with gross cystic breast disease (GCBD), although the mechanism for this increase remains unexplained. Relationships between GCBD characteristics, breast cancer risk factors, and the biochemical composition and growth properties of 142 breast cyst fluid (BCF) samples were studied among 93 women with GCBD. Concentrations of melatonin, estrogen (17-beta-estradiol), dehydroepiandrosterone-sulfate (DHEA-S), epidermal growth factor (EGF), transforming growth factor beta (TGF-B1 and TGF-B2), sodium (Na), and potassium (K) were quantified in BCF samples, and human breast cancer cells (MCF-7) were treated with BCF in vitro. Patients were grouped according to BCF Na:K ratios previously linked with increased breast cancer risks (Na:K 3, Type 2) and mixed cyst groups. Women with larger and more frequently occurring cysts had higher BCF estrogen and DHEA-S, and lower TGF-B1 levels. Women with Type 1 cysts had elevated BCF melatonin, estrogen, DHEA-S, and EGF, and lower concentrations of TGF-B2 compared to women with Type 2 cysts. BCF generally inhibited cell growth relative to serum-treated controls, consistent with previous studies. Melatonin and estrogen in BCF independently predicted growth inhibition and stimulation, respectively. Biological monitoring of BCF may help identify women with GCBD at greatest risk for breast cancer development.

Dendritic cells from malaria-infected mice are fully functional APC.

Malaria infection has long been associated with diminished T cell responses in vitro and more recently in experimental studies in vivo. Suppression of T cell-proliferative responses during malaria has been attributed to macrophages in a variety of murine and human systems. More recently, however, attention has been directed at the role of dendritic cells in this phenomenon, with several studies suggesting that maturation of dendritic cells is inhibited in vitro by the presence of malaria-infected E. In the studies reported here, we have examined the function of dendritic cells taken directly from infected mice. We found that they express high levels of costimulatory proteins and class II MHC, can activate naive T cells to produce IL-2 as efficiently as dendritic cells from uninfected mice, and support high levels of IFN-gamma production by naive T cells through an IL-12-dependent mechanism. Dendritic cells from infected mice also support higher levels of TNF-alpha production by naive T cells. These same dendritic cells present parasite Ag to a malaria-specific T cell hybridoma, a finding that demonstrates that dendritic cells participate in the generation of Ag-specific immunity during infection. Our findings challenge the contention that dendritic cell function is inhibited by malaria infection.